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AUTHOR Solis, Daphene Marques and Czekanski, Aleksander
Title 3D and 4D additive manufacturing techniques for vascular-like structures – A review [Abstract]
Year 2022
Journal/Proceedings Bioprinting
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The critical shortage in organ donors is a problem facing patients and health care systems worldwide. The most promising solution to this crisis is the artificial production of organs and tissues, known as tissue engineering. Significant advances in this field have led to the commercial production of artificial skin and cartilage, but limitations remain in the production of thicker tissues (i.e., >200 μm thickness). The challenge of producing thicker tissues relates to the inability to establish and maintain a vascular system, which is the basic requirement for artificially producing any vital organ. Given the importance of these structures, a major scientific effort is underway to better understand how to reproduce a vascular system. This review presents the most recent advances in the manufacturing of vascular-like structures, especially techniques involving additive manufacturing, or 3D and 4D printing. This review starts with a primer on the classification, composition, and mechanical proprieties of blood vessels, offering the reader a better understanding of the challenges involved in the artificial production of vessels. The review then discusses the methodologies, technologies, and materials used and available for the manufacturing of the vascular system.
AUTHOR Yang, Xue and Li, Shuai and Ren, Ya and Qiang, Lei and Liu, Yihao and Wang, Jinwu and Dai, Kerong
Title 3D printed hydrogel for articular cartilage regeneration [Abstract]
Year 2022
Journal/Proceedings Composites Part B: Engineering
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Tissue engineering is a promising strategy for damaged cartilage tissue repair. Three-dimensional (3D) printed hydrogel exhibits great potential in cartilage tissue engineering for fabricating 3D cell culture scaffolds, owing to its similarity to the extracellular matrix (ECM). Numerous hydrogels have been tested for 3D printing in vitro articular cartilage tissues, including natural and synthetic hydrogels that mimic their in vivo counterparts. The advancement of materials science and 3D printing techniques enables a wide range of fabrication strategies that produce cartilage tissues with delicate structures and on multiple scales. Stimuli-responsive hydrogels, which rely on the external environment to transform to a desired structure or dimension, have likewise been widely studied in tissue engineering. This review summarizes the characteristics, functions, and research conducted on 3D printed hydrogels by categorizing cutting-edge hydrogel materials commonly used in cartilage tissue engineering and their complexes. The challenges and application prospects of hydrogels in cartilage tissue engineering are described. Novel composite hydrogels must be investigated to meet the requirements of native articular cartilage in the aspects of structure, scale, mechanical properties, among others. Combining stimuli-responsive hydrogels with biological scaffolds also shows great potential in various applications, including but not limited to articular cartilage, vascularization, and osteochondral repair.
AUTHOR Müller, Florence J. and Fenton, Owen S.
Title Additive Manufacturing Approaches toward the Fabrication of Biomaterials [Abstract]
Year 2022
Journal/Proceedings Advanced Materials Interfaces
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Abstract The fabrication of biomaterials represents one methodology toward the creation of next generation therapies including organ and tissue replacements, drug delivery systems, and advanced pharmaceutical constructs. Overcoming challenges associated with their customization and personalization remains an area of active research. In this review, advances in the additive manufacture of biomaterials are highlighted. Specifically, topics including construct modeling, bioink selection, deposition strategy selection, and printed construct characterization are discussed. In exploring these areas, the aim of this review is to provide an overview of the biomaterials additive manufacturing process while also highlighting its application toward the betterment of human health.
AUTHOR Özcan, Mutlu and Magini, Eduarda Blasi and Volpato, Guilherme Maziero and Cruz, Ariadne and Volpato, Claudia Angela Maziero
Title Additive Manufacturing Technologies for Fabrication of Biomaterials for Surgical Procedures in Dentistry: A Narrative Review [Abstract]
Year 2022
Journal/Proceedings Journal of Prosthodontics
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Abstract Purpose To screen and critically appraise available literature regarding additive manufacturing technologies for bone graft material fabrication in dentistry. Material and Methods PubMed and Scopus were searched up to May 2021. Studies reporting the additive manufacturing techniques to manufacture scaffolds for intraoral bone defect reconstruction were considered eligible. A narrative review was synthesized to discuss the techniques for bone graft material fabrication in dentistry and the biomaterials used. Results The databases search resulted in 933 articles. After removing duplicate articles (128 articles), the titles and abstracts of the remaining articles (805 articles) were evaluated. A total of 89 articles were included in this review. Reading these articles, 5 categories of additive manufacturing techniques were identified: material jetting, powder bed fusion, vat photopolymerization, binder jetting, and material extrusion. Conclusions Additive manufacturing technologies for bone graft material fabrication in dentistry, especially 3D bioprinting approaches, have been successfully used to fabricate bone graft material with distinct compositions.
AUTHOR Wang, Haonan and Yu, Huaqing and Zhou, Xia and Zhang, Jilong and Zhou, Hongrui and Hao, Haitong and Ding, Lina and Li, Huiying and Gu, Yanru and Ma, Junchi and Qiu, Jianfeng and Ma, Depeng
Title An Overview of Extracellular Matrix-Based Bioinks for 3D Bioprinting [Abstract]
Year 2022
Journal/Proceedings Frontiers in Bioengineering and Biotechnology
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As a microenvironment where cells reside, the extracellular matrix (ECM) has a complex network structure and appropriate mechanical properties to provide structural and biochemical support for the surrounding cells. In tissue engineering, the ECM and its derivatives can mitigate foreign body responses by presenting ECM molecules at the interface between materials and tissues. With the widespread application of three-dimensional (3D) bioprinting, the use of the ECM and its derivative bioinks for 3D bioprinting to replicate biomimetic and complex tissue structures has become an innovative and successful strategy in medical fields. In this review, we summarize the significance and recent progress of ECM-based biomaterials in 3D bioprinting. Then, we discuss the most relevant applications of ECM-based biomaterials in 3D bioprinting, such as tissue regeneration and cancer research. Furthermore, we present the status of ECM-based biomaterials in current research and discuss future development prospects.
AUTHOR Shukla, Arvind Kumar and Gao, Ge and Kim, Byoung Soo
Title Applications of 3D Bioprinting Technology in Induced Pluripotent Stem Cells-Based Tissue Engineering [Abstract]
Year 2022
Journal/Proceedings Micromachines
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Induced pluripotent stem cells (iPSCs) are essentially produced by the genetic reprogramming of adult cells. Moreover, iPSC technology prevents the genetic manipulation of embryos. Hence, with the ensured element of safety, they rarely cause ethical concerns when utilized in tissue engineering. Several cumulative outcomes have demonstrated the functional superiority and potency of iPSCs in advanced regenerative medicine. Recently, an emerging trend in 3D bioprinting technology has been a more comprehensive approach to iPSC-based tissue engineering. The principal aim of this review is to provide an understanding of the applications of 3D bioprinting in iPSC-based tissue engineering. This review discusses the generation of iPSCs based on their distinct purpose, divided into two categories: (1) undifferentiated iPSCs applied with 3D bioprinting; (2) differentiated iPSCs applied with 3D bioprinting. Their significant potential is analyzed. Lastly, various applications for engineering tissues and organs have been introduced and discussed in detail.
AUTHOR Hermanová, Soňa and Pumera, Martin
Title Biodegradable polyester platform for extrusion-based bioprinting [Abstract]
Year 2022
Journal/Proceedings Bioprinting
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3D extrusion-based bioprinting has become an emerging tissue engineering technology to produce complex biomimetic structures for a reconstitution of living tissues. Simultaneous dispensing of two and more (bio)polymer materials affords the fabrication of functional 3D constructions displaying both bioactivity (bioink) and defined architecture and shape (scaffold frame). To fabricate biocompatible and biodegradable 3D scaffolds, aliphatic (co)polyesters are the materials of first choice. Recent progress has shown that the function of the polyester's frame can be expanded from contemporary mechanical support to a composite matrix with smart stimuli-responsive behavior. Consequently, it opens new avenues in the fabrication of multifunctional scaffolds, which can be designed as dynamic systems and/or delivery systems for bioactive molecules in situ. This minireview is focused on utilizing the most attractive representatives of aliphatic polyesters in the areas of bioartificial tissue/organ 3D and 4D bioprinting.
AUTHOR Taghizadeh, Mohsen and Taghizadeh, Ali and Yazdi, Mohsen Khodadadi and Zarrintaj, Payam and Stadler, Florian J. and Ramsey, Joshua D. and Habibzadeh, Sajjad and Hosseini Rad, Somayeh and Naderi, Ghasem and Saeb, Mohammad Reza and Mozafari, Masoud and Schubert, Ulrich S.
Title Chitosan-based inks for 3D printing and bioprinting [Abstract]
Year 2022
Journal/Proceedings Green Chem.
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The advent of 3D-printing/additive manufacturing in biomedical engineering field has introduced great potential for the preparation of 3D structures that can mimic native tissues. This technology has accelerated the progress in numerous areas of regenerative medicine{,} especially led to a big wave of biomimetic functional scaffold developments for tissue engineering demands. In recent years{,} the introduction of smart bio-inks has created growing efforts to facilitate the preparation of complex and homogeneous living-cell-containing 3D constructs. In the past decade{,} a considerable body of literature has been created on identifying an ideal bioinspired-ink with excellent printability{,} cell viability{,} bioactivity{,} and mechanical properties. This state-of-the-art review article briefly outlines 3D-printing/bioprinting techniques applied for chitosan-based bio-inks{,} their resources{,} crosslinking methods{,} characteristics{,} reasons for their superiority over other bio-inks{,} and challenges of commercialization; this is followed by a comprehensive description of the full potential and the key indicators of success in terms of 3D bio-printing of such bio-inks as platforms for tissue regeneration{,} advanced biosensors{,} drug delivery{,} and wastewater treatment. Next{,} the restrictions and challenges of chitosan bio-inks are highlighted. In this work{,} we also discussed about developing a coherent research strategy based on combination of microfluidics-based lab-on-a-chip (organ-on-a-chip) platforms with 3D-bioprinting which enables designing of self-healing scaffolds. And finally{,} the potential of smart inks based on chitosan for 4D bioprinting of more detailed and practical engineered tissues and artificial organs is reviewed.
AUTHOR Gonzalez, Gustavo and Roppolo, Ignazio and Pirri, Candido Fabrizio and Chiappone, Annalisa
Title Current and emerging trends in polymeric 3D printed microfluidic devices [Abstract]
Year 2022
Journal/Proceedings Additive Manufacturing
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During the last two decades, 3D printing technology has emerged as a valid alternative for producing microfluidic devices. 3D printing introduces new strategies to obtain high precision microfluidic parts without complex tooling and equipment, making the production of microfluidic devices cheaper, faster, and easier than conventional fabrication methods such as soft lithography. Among the main 3D techniques used for this purpose, fused filament manufacturing (FFF), inkjet 3D printing (i3Dp) and vat polymerization (VP) are of the greatest interest since they are well-established techniques in the field and are cost-affordable both in equipment and material. However, there are still some barriers in terms of technology and materials to overtake for definitively establishing 3D printing as a truly microfluidic production method. For example, the level of resolution and precision of 3D printed microfluidic parts still does not reach the level of conventional fabrication techniques, and, from a materialistic point of view, few materials present the desired characteristics (e.g., biocompatibility, optical transparency, and mechanical properties) for target areas such as medicine, analytical chemistry, and pharmaceuticals. This review intends to evaluate and analyze the current state of polymeric 3D printing techniques and materials to manufacture microfluidic chips. The article will show and discuss the latest innovations, materials, and applications of such 3D printed microstructures. The focus of this review is to provide an overview of recent and future developments in 3D printing and materials in the branch of microfluidics fabrications, showing that the selection of the right materials together with the design freedom afforded by 3D printing will be the cornerstone for microfluidic development.
AUTHOR Ke, Dongxu and Niu, Changmei and Yang, Xi
Title Evolution of 3D bioprinting-from the perspectives of bioprinting companies [Abstract]
Year 2022
Journal/Proceedings Bioprinting
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3D bioprinting is an advanced additive manufacturing approach evolved from traditional 3D printing to fulfill specific requirements for the applications of tissue engineering and regenerative medicine. During the past decade, bioprinting has progressed substantially showing its extraordinary potential for applications in different biomedical fields, however, a huge gap still exists for the large-scale industrialization and commercialization of this technology. In this review article, we will first discuss several successful bioprinting companies and their current efforts on the commercialization of bioprinting technology. Then future challenges that restrict the application of bioprinting will be discussed. Finally, we will conclude several key factors, which inhibit the translational development of bioprinting, while should be addressed soon.
AUTHOR Mota, Fabio Batista and Braga, Luiza Amara Maciel and Cabral, Bernardo Pereira and Filho, Carlos Gilbert Conte
Title Future of Bioprinted Tissues аnd Organs: A Two-Wave Global Survey [Abstract]
Year 2022
Journal/Proceedings Foresight and STI Governance
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Technologies of 3D and 4D bioprinting make it possible to restore or replace tissues and organs, solving the problem of the lack of donor resources and reducing the risks of implant rejection. This article presents the results of a two-stage global survey of specialists in tissue engineering on the prospects of bioprinting in preclinical studies and clinical practice. A picture of possible tracks and horizons upon which the implementation of the considered solutions is possible is presented. According to the results of the survey, in the next two decades it will be possible to recreate tissues and organs suitable for implantation and drug testing. There will be a market for bioprinted products, the problem of organ shortages and adverse reactions to drugs will be solved. These changes may significantly affect not only the practice of biomedical research, drug testing, and medicine, but also the healthcare sector in general, which implies the need for a preventive review of current policies. A practical and accessible tool for identifying and interviewing a large number of experts around the world is proposed, which may be useful for new Foresight studies.
AUTHOR Pazhouhnia, Zahra and Beheshtizadeh, Nima and Namini, Mojdeh Salehi and Lotfibakhshaiesh, Nasrin
Title Portable hand-held bioprinters promote in situ tissue regeneration [Abstract]
Year 2022
Journal/Proceedings Bioengineering & Translational Medicine
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Abstract Three-dimensional bioprinting, as a novel technique of fabricating engineered tissues, is positively correlated with the ultimate goal of regenerative medicine, which is the restoration, reconstruction, and repair of lost and/or damaged tissue function. The progressive trend of this technology resulted in developing the portable hand-held bioprinters, which could be used quite easily by surgeons and physicians. With the advent of portable hand-held bioprinters, the obstacles and challenges of utilizing statistical bioprinters could be resolved. This review attempts to discuss the advantages and challenges of portable hand-held bioprinters via in situ tissue regeneration. All the tissues that have been investigated by this approach were reviewed, including skin, cartilage, bone, dental, and skeletal muscle regeneration, while the tissues that could be regenerated via this approach are targeted in the authors' perspective. The design and applications of hand-held bioprinters were discussed widely, and the marketed printers were introduced. It has been prospected that these facilities could ameliorate translating the regenerative medicine science from the bench to the bedside actively.
AUTHOR Betancourt, Nicholas and Chen, Xiongbiao
Title Review of extrusion-based multi-material bioprinting processes [Abstract]
Year 2022
Journal/Proceedings Bioprinting
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Scaffold-based tissue engineering aims to provide patients with permanent solutions to damaged organs and tissues based on engineered scaffolds. For this, extrusion-based bioprinting has drawn considerable attention for scaffold fabrication due to its ability to print a variety of biomaterials or their mixtures with living cells, as well as its simple construction and operation. Incorporating multiple materials is essential, yet challenging, in the bioprinting process to mimic the heterogeneous and anisotropic structure and properties of native tissue. This paper reviews the extrusion-based bioprinting process that employs varying approaches or mechanisms to print multiple materials and living cells, including side-by-side printing, core-and-shell printing, and recently developed advanced bioprinting methods. Key issues in this research area are also identified and discussed, along with recommendations for future research.
AUTHOR Tutty, Melissa Anne and Movia, Dania and Prina-Mello, Adriele
Title Three-dimensional (3D) liver cell models - a tool for bridging the gap between animal studies and clinical trials when screening liver accumulation and toxicity of nanobiomaterials [Abstract]
Year 2022
Journal/Proceedings Drug Delivery and Translational Research
Reftype Tutty2022
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Despite the exciting properties and wide-reaching applications of nanobiomaterials (NBMs) in human health and medicine, their translation from bench to bedside is slow, with a predominant issue being liver accumulation and toxicity following systemic administration. In vitro 2D cell-based assays and in vivo testing are the most popular and widely used methods for assessing liver toxicity at pre-clinical stages; however, these fall short in predicting toxicity for NBMs. Focusing on in vitro and in vivo assessment, the accurate prediction of human-specific hepatotoxicity is still a significant challenge to researchers. This review describes the relationship between NBMs and the liver, and the methods for assessing toxicity, focusing on the limitations they bring in the assessment of NBM hepatotoxicity as one of the reasons defining the poor translation for NBMs. We will then present some of the most recent advances towards the development of more biologically relevant in vitro liver methods based on tissue-mimetic 3D cell models and how these could facilitate the translation of NBMs going forward. Finally, we also discuss the low public acceptance and limited uptake of tissue-mimetic 3D models in pre-clinical assessment, despite the demonstrated technical and ethical advantages associated with them.
AUTHOR Blume, Cornelia and Kraus, Xenia and Heene, Sebastian and Loewner, Sebastian and Stanislawski, Nils and Cholewa, Fabian and Blume, Holger
Title Vascular implants – new aspects for in situ tissue engineering [Abstract]
Year 2022
Journal/Proceedings Engineering in Life Sciences
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Abstract Conventional synthetic vascular grafts require ongoing anticoagulation, and autologous venous grafts are often not available in elderly patients. This review highlights the development of bioartificial vessels replacing brain-dead donor- or animal-deriving vessels with ongoing immune reactivity. The vision for such bio-hybrids exists in a combination of biodegradable scaffolds and seeding with immune-neutral cells, and here different cells sources such as autologous progenitor cells or stem cells are relevant. This kind of in situ tissue engineering depends on a suitable bioreactor system with elaborate monitoring systems, three-dimensional (3D) visualization and a potential of cell conditioning into the direction of the targeted vascular cell phenotype. Necessary bioreactor tools for dynamic and pulsatile cultivation are described. In addition, a concept for design of vasa vasorum is outlined, that is needed for sustainable nutrition of the wall structure in large caliber vessels. For scaffold design and cell adhesion additives, different materials and technologies are discussed. 3D printing is introduced as a relatively new field with promising prospects, for example, to create complex geometries or micro-structured surfaces for optimal cell adhesion and ingrowth in a standardized and custom designed procedure. Summarizing, a bio-hybrid vascular prosthesis from a controlled biotechnological process is thus coming more and more into view. It has the potential to withstand strict approval requirements applied for advanced therapy medicinal products.
AUTHOR Soleymani Eil Bakhtiari, Sanaz and Bakhsheshi-Rad, Hamid Reza and Karbasi, Saeed and Razzaghi, Mahmood and Tavakoli, Mohamadreza and Ismail, Ahmad Fauzi and Sharif, Safian and RamaKrishna, Seeram and Chen, Xiongbiao and Berto, Filippo
Title 3-Dimensional Printing of Hydrogel-Based Nanocomposites: A Comprehensive Review on the Technology Description, Properties, and Applications [Abstract]
Year 2021
Journal/Proceedings Advanced Engineering Materials
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Increasing demand for customized implants and tissue scaffolds requires advanced biomaterials and fabricating processes for fabricating three-dimensional (3D) structures that resemble the complexity of the extracellular matrix (ECM). Lately, biofabrication approaches such as cell-laden (soft) hydrogel 3D printing (3DP) have been of increasing interest in the development of 3D functional environments similar to natural tissues and organs. Hydrogels that resemble biological ECMs can provide mechanical support and signaling cues to cells to control their behavior. Although the capability of hydrogels to produce artificial ECMs can regulate cellular behavior, one of the major drawbacks of working with hydrogels is their inferior mechanical properties. Therefore, keeping and enhancing the mechanical integrity of fabricated scaffolds has become an essential matter for 3D hydrogel structures. Herein, 3D-printed hydrogel-based nanocomposites (NCs) are evaluated systematically in terms of introducing novel techniques for 3DP of hydrogel-based materials, properties, and biomedical applications.
AUTHOR Ramadan, Qasem and Zourob, Mohammed
Title 3D Bioprinting at the Frontier of Regenerative Medicine, Pharmaceutical, and Food Industries [Abstract]
Year 2021
Journal/Proceedings Frontiers in Medical Technology
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3D printing technology has emerged as a key driver behind an ongoing paradigm shift in the production process of various industrial domains. The integration of 3D printing into tissue engineering, by utilizing life cells which are encapsulated in specific natural or synthetic biomaterials (e.g., hydrogels) as bioinks, is paving the way toward devising many innovating solutions for key biomedical and healthcare challenges and heralds' new frontiers in medicine, pharmaceutical, and food industries. Here, we present a synthesis of the available 3D bioprinting technology from what is found and what has been achieved in various applications and discussed the capabilities and limitations encountered in this technology.
AUTHOR Das,Sanskrita and Nam,Hyoryung and Jang,Jinah
Title 3D bioprinting of stem cell-laden cardiac patch: A promising alternative for myocardial repair
Year 2021
Journal/Proceedings APL Bioengineering
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AUTHOR Zhang, Yi and Wang, Bin and Hu, Junchao and Yin, Tianyuan and Yue, Tao and Liu, Na and Liu, Yuanyuan
Title 3D Composite Bioprinting for Fabrication of Artificial Biological Tissues. [Abstract]
Year 2021
Journal/Proceedings International journal of bioprinting
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Three-dimensional (3D) bioprinting is an important technology for fabricating artificial tissue. To effectively reconstruct the multiscale structure and multi-material gradient of natural tissues and organs, 3D bioprinting has been increasingly developed into multi-process composite mode. The current 3D composite bioprinting is a combination of two or more printing processes, and oftentimes, physical field regulation that can regulate filaments or cells during or after printing may be involved. Correspondingly, both path planning strategy and process control all become more complex. Hence, the computer-aided design and computer-aided manufacturing (CAD/CAM) system that is traditionally used in 3D printing system is now facing challenges. Thus, the scale information that cannot be modeled in the CAD process should be considered in the design of CAM by adding a process management module in the traditional CAD/CAM system and add more information reflecting component gradient in the path planning strategy.
AUTHOR Shende, Pravin and Trivedi, Riddhi
Title 3D Printed Bioconstructs: Regenerative Modulation for Genetic Expression [Abstract]
Year 2021
Journal/Proceedings Stem Cell Reviews and Reports
Reftype Shende2021
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Layer-by-layer deposition of cells, tissues and similar molecules provided by additive manufacturing techniques such as 3D bioprinting offers safe, biocompatible, effective and inert methods for the production of biological structures and biomimetic scaffolds. 3D bioprinting assisted through computer programmes and software develops mutli-modal nano- or micro-particulate systems such as biosensors, dosage forms or delivery systems and other biological scaffolds like pharmaceutical implants, prosthetics, etc. This review article focuses on the implementation of 3D bioprinting techniques in the gene expression, in gene editing or therapy and in delivery of genes. The applications of 3D printing are extensive and include gene therapy, modulation and expression in cancers, tissue engineering, osteogenesis, skin and vascular regeneration. Inclusion of nanotechnology with genomic bioprinting parameters such as gene conjugated or gene encapsulated 3D printed nanostructures may offer new avenues in the future for efficient and controlled treatment and help in overcoming the limitations faced in conventional methods. Moreover, expansion of the benefits from such techniques is advantageous in real-time delivery or in-situ production of nucleic acids into the host cells.
AUTHOR Seydel, Caroline
Title 3D-Bioprinted Cell Therapy and Disease Modeling Applications
Year 2021
Journal/Proceedings Genetic Engineering & Biotechnology News
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AUTHOR Finny, Abraham Samuel and Popoola, Oluwatosin and Andreescu, Silvana
Title 3D-Printable Nanocellulose-Based Functional Materials: Fundamentals and Applications [Abstract]
Year 2021
Journal/Proceedings Nanomaterials
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Nanomaterials obtained from sustainable and natural sources have seen tremendous growth in recent times due to increasing interest in utilizing readily and widely available resources. Nanocellulose materials extracted from renewable biomasses hold great promise for increasing the sustainability of conventional materials in various applications owing to their biocompatibility, mechanical properties, ease of functionalization, and high abundance. Nanocellulose can be used to reinforce mechanical strength, impart antimicrobial activity, provide lighter, biodegradable, and more robust materials for packaging, and produce photochromic and electrochromic devices. While the fabrication and properties of nanocellulose are generally well established, their implementation in novel products and applications requires surface modification, assembly, and manufacturability to enable rapid tooling and scalable production. Additive manufacturing techniques such as 3D printing can improve functionality and enhance the ability to customize products while reducing fabrication time and wastage of materials. This review article provides an overview of nanocellulose as a sustainable material, covering the different properties, preparation methods, printability and strategies to functionalize nanocellulose into 3D-printed constructs. The applications of 3D-printed nanocellulose composites in food, environmental, and energy devices are outlined, and an overview of challenges and opportunities is provided.
AUTHOR Tarassoli, Sam P. and Jessop, Zita M. and Jovic, Thomas and Hawkins, Karl and Whitaker, Iain S.
Title Candidate Bioinks for Extrusion 3D Bioprinting—A Systematic Review of the Literature [Abstract]
Year 2021
Journal/Proceedings Frontiers in Bioengineering and Biotechnology
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Purpose: Bioprinting is becoming an increasingly popular platform technology for engineering a variety of tissue types. Our aim was to identify biomaterials that have been found to be suitable for extrusion 3D bioprinting, outline their biomechanical properties and biocompatibility towards their application for bioprinting specific tissue types. This systematic review provides an in-depth overview of current biomaterials suitable for extrusion to aid bioink selection for specific research purposes and facilitate design of novel tailored bioinks.Methods: A systematic search was performed on EMBASE, PubMed, Scopus and Web of Science databases according to the PRISMA guidelines. References of relevant articles, between December 2006 to January 2018, on candidate bioinks used in extrusion 3D bioprinting were reviewed by two independent investigators against standardised inclusion and exclusion criteria. Data was extracted on bioprinter brand and model, printing technique and specifications (speed and resolution), bioink material and class of mechanical assessment, cell type, viability, and target tissue. Also noted were authors, study design (in vitro/in vivo), study duration and year of publication.Results: A total of 9,720 studies were identified, 123 of which met inclusion criteria, consisting of a total of 58 reports using natural biomaterials, 26 using synthetic biomaterials and 39 using a combination of biomaterials as bioinks. Alginate (n = 50) and PCL (n = 33) were the most commonly used bioinks, followed by gelatin (n = 18) and methacrylated gelatin (GelMA) (n = 16). Pneumatic extrusion bioprinting techniques were the most common (n = 78), followed by piston (n = 28). The majority of studies focus on the target tissue, most commonly bone and cartilage, and investigate only one bioink rather than assessing a range to identify those with the most promising printability and biocompatibility characteristics. The Bioscaffolder (GeSiM, Germany), 3D Discovery (regenHU, Switzerland), and Bioplotter (EnvisionTEC, Germany) were the most commonly used commercial bioprinters (n = 35 in total), but groups most often opted to create their own in-house devices (n = 20). Many studies also failed to specify whether the mechanical data reflected pre-, during or post-printing, pre- or post-crosslinking and with or without cells.Conclusions: Despite the continued increase in the variety of biocompatible synthetic materials available, there has been a shift change towards using natural rather than synthetic bioinks for extrusion bioprinting, dominated by alginate either alone or in combination with other biomaterials. On qualitative analysis, no link was demonstrated between the type of bioink or extrusion technique and the target tissue, indicating that bioprinting research is in its infancy with no established tissue specific bioinks or bioprinting techniques. Further research is needed on side-by-side characterisation of bioinks with standardisation of the type and timing of biomechanical assessment.
AUTHOR Shiwarski,Daniel J. and Hudson,Andrew R. and Tashman,Joshua W. and Feinberg,Adam W.
Title Emergence of FRESH 3D printing as a platform for advanced tissue biofabrication
Year 2021
Journal/Proceedings APL Bioengineering
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AUTHOR Ravanbakhsh, Hossein and Karamzadeh, Vahid and Bao, Guangyu and Mongeau, Luc and Juncker, David and Zhang, Yu Shrike
Title Emerging Technologies in Multi-Material Bioprinting [Abstract]
Year 2021
Journal/Proceedings Advanced Materials
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Abstract Bioprinting, within the emerging field of biofabrication, aims at the fabrication of functional biomimetic constructs. Different 3D bioprinting techniques have been adapted to bioprint cell-laden bioinks. However, single-material bioprinting techniques oftentimes fail to reproduce the complex compositions and diversity of native tissues. Multi-material bioprinting as an emerging approach enables the fabrication of heterogeneous multi-cellular constructs that replicate their host microenvironments better than single-material approaches. Here, bioprinting modalities are reviewed, their being adapted to multi-material bioprinting is discussed, and their advantages and challenges, encompassing both custom-designed and commercially available technologies are analyzed. A perspective of how multi-material bioprinting opens up new opportunities for tissue engineering, tissue model engineering, therapeutics development, and personalized medicine is offered.
AUTHOR Kjar, Andrew and McFarland, Bailey and Mecham, Keetch and Harward, Nathan and Huang, Yu
Title Engineering of tissue constructs using coaxial bioprinting [Abstract]
Year 2021
Journal/Proceedings Bioactive Materials
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Bioprinting is a rapidly developing technology for the precise design and manufacture of tissues in various biological systems or organs. Coaxial extrusion bioprinting, an emergent branch, has demonstrated a strong potential to enhance bioprinting's engineering versatility. Coaxial bioprinting assists in the fabrication of complex tissue constructs, by enabling concentric deposition of biomaterials. The fabricated tissue constructs started with simple, tubular vasculature but have been substantially developed to integrate complex cell composition and self-assembly, ECM patterning, controlled release, and multi-material gradient profiles. This review article begins with a brief overview of coaxial printing history, followed by an introduction of crucial engineering components. Afterward, we review the recent progress and untapped potential in each specific organ or biological system, and demonstrate how coaxial bioprinting facilitates the creation of tissue constructs. Ultimately, we conclude that this growing technology will contribute significantly to capabilities in the fields of in vitro modeling, pharmaceutical development, and clinical regenerative medicine.
AUTHOR Firipis, Kate and Nisbet, David R. and Franks, Stephanie J. and Kapsa, Robert M. I. and Pirogova, Elena and Williams, Richard J. and Quigley, Anita
Title Enhancing Peptide Biomaterials for Biofabrication [Abstract]
Year 2021
Journal/Proceedings Polymers
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Biofabrication using well-matched cell/materials systems provides unprecedented opportunities for dealing with human health issues where disease or injury overtake the body’s native regenerative abilities. Such opportunities can be enhanced through the development of biomaterials with cues that appropriately influence embedded cells into forming functional tissues and organs. In this context, biomaterials’ reliance on rigid biofabrication techniques needs to support the incorporation of a hierarchical mimicry of local and bulk biological cues that mimic the key functional components of native extracellular matrix. Advances in synthetic self-assembling peptide biomaterials promise to produce reproducible mimics of tissue-specific structures and may go some way in overcoming batch inconsistency issues of naturally sourced materials. Recent work in this area has demonstrated biofabrication with self-assembling peptide biomaterials with unique biofabrication technologies to support structural fidelity upon 3D patterning. The use of synthetic self-assembling peptide biomaterials is a growing field that has demonstrated applicability in dermal, intestinal, muscle, cancer and stem cell tissue engineering.
AUTHOR Tarun Agarwal and Marco Costantini and Tapas Kumar Maiti
Title Extrusion 3D printing with Pectin-based ink formulations: Recent trends in tissue engineering and food manufacturing [Abstract]
Year 2021
Journal/Proceedings Biomedical Engineering Advances
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3D printing technologies are rapidly revolutionizing all manufacturing sectors due to their ability to create objects with complex geometries in a reproducible and automated manner using material/cell-based formulations, precisely termed printing inks. In this regard, pectin, a naturally occurring plant polysaccharide, has been proposed as a potential component of ink formulations. In this mini-review, we would overview the most recent advances made with pectin-based inks in the fields of tissue engineering and food manufacturing. We also discuss various strategies used to formulate 3D printable pectin inks. Finally, various challenges and prospects for future development are discussed.
AUTHOR King, William E. and Bowlin, Gary L.
Title Near-Field Electrospinning and Melt Electrowriting of Biomedical Polymers—Progress and Limitations [Abstract]
Year 2021
Journal/Proceedings Polymers
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Near-field electrospinning (NFES) and melt electrowriting (MEW) are the process of extruding a fiber due to the force exerted by an electric field and collecting the fiber before bending instabilities occur. When paired with precise relative motion between the polymer source and the collector, a fiber can be directly written as dictated by preprogrammed geometry. As a result, this precise fiber control results in another dimension of scaffold tailorability for biomedical applications. In this review, biomedically relevant polymers that to date have manufactured fibers by NFES/MEW are explored and the present limitations in direct fiber writing of standardization in published setup details, fiber write throughput, and increased ease in the creation of complex scaffold geometries are discussed.
AUTHOR Yadav, Chandravati and Saini, Arun and Zhang, Wenbo and You, Xiangyu and Chauhan, Indu and Mohanty, Paritosh and Li, Xinping
Title Plant-based nanocellulose: A review of routine and recent preparation methods with current progress in its applications as rheology modifier and 3D bioprinting [Abstract]
Year 2021
Journal/Proceedings International Journal of Biological Macromolecules
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Abstract
“Nanocellulose” have captivated the topical sphere of sturdily escalating market for sustainable materials. The review focuses on the comprehensive understanding of the distinct surface chemistry and functionalities pertaining to the renovation of macro-cellulose at nanodimensional scale to provide an intuition of their processing-structure-function prospective. The abundant availability, cost effectiveness and diverse properties associated with plant-based resources have great economical perspective for developing sustainable cellulose nanomaterials. Hence, emphasis has been given on nanocellulose types obtained from plant-based sources. An overarching goal is to provide the recent advancement in the preparation routes of nanocellulose. Considering the excellent shear thinning/thixotropic/gel-like behavior, the review provids an assemblage of publications specifically dealing with its application as rheology modifier with emphasis on its use as bioink for 3D bioprinting for various biomedical applications. Altogether, this review has been oriented in a way to collocate a collective data starting from the historical perspective of cellulose discovery to modern cellulosic chemistry and its renovation as nanocellulose with recent technological hype for broad spanning applications.
AUTHOR Balaji Mahendiran and Shalini Muthusamy and Sowndarya Sampath and S.N. Jaisankar and Ketul C. Popat and R. Selvakumar and Gopal Shankar Krishnakumar
Title Recent trends in natural polysaccharide based bioinks for multiscale 3D printing in tissue regeneration: A review [Abstract]
Year 2021
Journal/Proceedings International Journal of Biological Macromolecules
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Abstract
Biofabrication by three-dimensional (3D) printing has been an attractive technology in harnessing the possibility to print anatomical shaped native tissues with controlled architecture and resolution. 3D printing offers the possibility to reproduce complex microarchitecture of native tissues by printing live cells in a layer by layer deposition to provide a biomimetic structural environment for tissue formation and host tissue integration. Plant based biomaterials derived from green and sustainable sources have represented to emulate native physicochemical and biological cues in order to direct specific cellular response and formation of new tissues through biomolecular recognition patterns. This comprehensive review aims to analyze and identify the most commonly used plant based bioinks for 3D printing applications. An overview on the role of different plant based biomaterial of terrestrial origin (Starch, Nanocellulose and Pectin) and marine origin (Ulvan, Alginate, Fucoidan, Agarose and Carrageenan) used for 3D printing applications are discussed elaborately. Furthermore, this review will also emphasis in the functional aspects of different 3D printers, appropriate printing material, merits and demerits of numerous plant based bioinks in developing 3D printed tissue-like constructs. Additionally, the underlying potential benefits, limitations and future perspectives of plant based bioinks for tissue engineering (TE) applications are also discussed.
AUTHOR Moghaddam, Abolfazl Salehi and Khonakdar, Hossein Ali and Arjmand, Mohammad and Jafari, Seyed Hassan and Bagher, Zohreh and Moghaddam, Zahra Salehi and Chimerad, Mohammadreza and Sisakht, Mahsa Mollapour and Shojaei, Shahrokh
Title Review of Bioprinting in Regenerative Medicine: Naturally Derived Bioinks and Stem Cells [Abstract]
Year 2021
Journal/Proceedings ACS Appl. Bio Mater.
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Regenerative medicine offers the potential to repair or substitute defective tissues by constructing active tissues to address the scarcity and demands for transplantation. The method of forming 3D constructs made up of biomaterials, cells, and biomolecules is called bioprinting. Bioprinting of stem cells provides the ability to reliably recreate tissues, organs, and microenvironments to be used in regenerative medicine. 3D bioprinting is a technique that uses several biomaterials and cells to tailor a structure with clinically relevant geometries and sizes. This technique’s promise is demonstrated by 3D bioprinted tissues, including skin, bone, cartilage, and cardiovascular, corneal, hepatic, and adipose tissues. Several bioprinting methods have been combined with stem cells to effectively produce tissue models, including adult stem cells, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and differentiation techniques. In this review, technological challenges of printed stem cells using prevalent naturally derived bioinks (e.g., carbohydrate polymers and protein-based polymers, peptides, and decellularized extracellular matrix), recent advancements, leading companies, and clinical trials in the field of 3D bioprinting are delineated. Regenerative medicine offers the potential to repair or substitute defective tissues by constructing active tissues to address the scarcity and demands for transplantation. The method of forming 3D constructs made up of biomaterials, cells, and biomolecules is called bioprinting. Bioprinting of stem cells provides the ability to reliably recreate tissues, organs, and microenvironments to be used in regenerative medicine. 3D bioprinting is a technique that uses several biomaterials and cells to tailor a structure with clinically relevant geometries and sizes. This technique’s promise is demonstrated by 3D bioprinted tissues, including skin, bone, cartilage, and cardiovascular, corneal, hepatic, and adipose tissues. Several bioprinting methods have been combined with stem cells to effectively produce tissue models, including adult stem cells, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and differentiation techniques. In this review, technological challenges of printed stem cells using prevalent naturally derived bioinks (e.g., carbohydrate polymers and protein-based polymers, peptides, and decellularized extracellular matrix), recent advancements, leading companies, and clinical trials in the field of 3D bioprinting are delineated.
AUTHOR Anh Tong and Quang Long Pham and Paul Abatemarco and Austin Mathew and Dhruv Gupta and Siddharth Iyer and Roman Voronov
Title Review of Low-Cost 3D Bioprinters: State of the Market and Observed Future Trends [Abstract]
Year 2021
Journal/Proceedings SLAS TECHNOLOGY: Translating Life Sciences Innovation
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Three-dimensional (3D) bioprinting has become mainstream for precise and repeatable high-throughput fabrication of complex cell cultures and tissue constructs in drug testing and regenerative medicine, food products, dental and medical implants, biosensors, and so forth. Due to this tremendous growth in demand, an overwhelming amount of hardware manufacturers have recently flooded the market with different types of low-cost bioprinter models—a price segment that is most affordable to typical-sized laboratories. These machines range in sophistication, type of the underlying printing technology, and possible add-ons/features, which makes the selection process rather daunting (especially for a nonexpert customer). Yet, the review articles available in the literature mostly focus on the technical aspects of the printer technologies under development, as opposed to explaining the differences in what is already on the market. In contrast, this paper provides a snapshot of the fast-evolving low-cost bioprinter niche, as well as reputation profiles (relevant to delivery time, part quality, adherence to specifications, warranty, maintenance, etc.) of the companies selling these machines. Specifically, models spanning three dominant technologies—microextrusion, droplet-based/inkjet, and light-based/crosslinking—are reviewed. Additionally, representative examples of high-end competitors (including up-and-coming microfluidics-based bioprinters) are discussed to highlight their major differences and advantages relative to the low-cost models. Finally, forecasts are made based on the trends observed during this survey, as to the anticipated trickling down of the high-end technologies to the low-cost printers. Overall, this paper provides insight for guiding buyers on a limited budget toward making informed purchasing decisions in this fast-paced market.
AUTHOR Li, Mei-Chun and Wu, Qinglin and Moon, Robert J. and Hubbe, Martin A. and Bortner, Michael J.
Title Rheological Aspects of Cellulose Nanomaterials: Governing Factors and Emerging Applications [Abstract]
Year 2021
Journal/Proceedings Advanced Materials
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Abstract Cellulose nanomaterials (CNMs), mainly including nanofibrillated cellulose (NFC) and cellulose nanocrystals (CNCs), have attained enormous interest due to their sustainability, biodegradability, biocompatibility, nanoscale dimensions, large surface area, facile modification of surface chemistry, as well as unique optical, mechanical, and rheological performance. One of the most fascinating properties of CNMs is their aqueous suspension rheology, i.e., CNMs helping create viscous suspensions with the formation of percolation networks and chemical interactions (e.g., van der Waals forces, hydrogen bonding, electrostatic attraction/repulsion, and hydrophobic attraction). Under continuous shearing, CNMs in an aqueous suspension can align along the flow direction, producing shear-thinning behavior. At rest, CNM suspensions regain some of their initial structure immediately, allowing rapid recovery of rheological properties. These unique flow features enable CNMs to serve as rheological modifiers in a wide range of fluid-based applications. Herein, the dependence of the rheology of CNM suspensions on test protocols, CNM inherent properties, suspension environments, and postprocessing is systematically described. A critical overview of the recent progress on fluid applications of CNMs as rheology modifiers in some emerging industrial sectors is presented as well. Future perspectives in the field are outlined to guide further research and development in using CNMs as the next generation rheological modifiers.
AUTHOR Justino Netto, Joaquim Manoel and Idogava, Henrique Takashi and Frezzatto Santos, Luiz Eduardo and Silveira, Zilda de Castro and Romio, Pedro and Alves, Jorge Lino
Title Screw-assisted 3D printing with granulated materials: a systematic review [Abstract]
Year 2021
Journal/Proceedings The International Journal of Advanced Manufacturing Technology
Reftype Justino Netto2021
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This paper presents a systematic review on extrusion additive manufacturing (EAM), with focus on the technological development of screw-assisted systems that can be fed directly with granulated materials. Screw-assisted EAM has gained importance as an enabling technology to expand the range of 3D printing materials, reduce costs associated with feedstock fabrication, and increase the material deposition rate compared to traditional fused filament fabrication (FFF). Many experimental printheads and commercial systems that use some screw-processing mechanism can be found in the literature, but the design diversity and lack of standard terminology make it difficult to determine the most suitable solutions for a given material or application field. Besides, the few previous reviews have offered only a glimpse into the topic, without an in-depth analysis about the design of the extruders and associated capabilities. A systematic procedure was devised to identify the screw-assisted EAM systems that can print directly from granulated materials, resulting in 61 articles describing different pieces of equipment that were categorized as experimental printheads and commercial systems, for small- and large-scale applications. After describing their main characteristics, the most significant extruder modifications were discussed with reference to the materials processed and performance requirements. In the end, a general workflow for the development of 3D printers based on screw extrusion was proposed. This review intends to provide information about the state-of-the-art screw-assisted EAM and help the academy to identify further research opportunities in the field.
AUTHOR Iria Seoane-Viaño and Patricija Januskaite and Carmen Alvarez-Lorenzo and Abdul W. Basit and Alvaro Goyanes
Title Semi-solid extrusion 3D printing in drug delivery and biomedicine: Personalised solutions for healthcare challenges [Abstract]
Year 2021
Journal/Proceedings Journal of Controlled Release
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Three-dimensional (3D) printing is an innovative additive manufacturing technology, capable of fabricating unique structures in a layer-by-layer manner. Semi-solid extrusion (SSE) is a subset of material extrusion 3D printing, and through the sequential deposition of layers of gel or paste creates objects of any desired size and shape. In comparison to other extrusion-based technologies, SSE 3D printing employs low printing temperatures which makes it suitable for drug delivery and biomedical applications, and the use of disposable syringes provides benefits in meeting critical quality requirements for pharmaceutical use. Besides pharmaceutical manufacturing, SSE 3D printing has attracted increasing attention in the field of bioelectronics, particularly in the manufacture of biosensors capable of measuring physiological parameters or as a means to trigger drug release from medical devices. This review begins by highlighting the major printing process parameters and material properties that influence the feasibility of transforming a 3D design into a 3D object, and follows with a discussion on the current SSE 3D printing developments and their applications in the fields of pharmaceutics, bioprinting and bioelectronics. Finally, the advantages and limitations of this technology are explored, before focusing on its potential clinical applications and suitability for preparing personalised medicines.
AUTHOR Bicudo, Edison and Faulkner, Alex and Li, Phoebe
Title Software, risks, and liabilities: ongoing and emergent issues in 3D bioprinting [Abstract]
Year 2021
Journal/Proceedings Journal of Risk Research
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AbstractThe growing use of software in biomedicine has enlarged the capacities of researchers and clinicians. This, one might expect, would enhance the precision and safety of biomedicine. However, it has been recognized that software can bring about new risks to the field of medicine and medical devices, requiring at least some degree of caution from the different players responsible for technology governance and risk management. This phenomenon is focused on in this paper, from the viewpoint of 3D bioprinting.Bioprinting is the production of bioactive structures in a layer-by-layer deposition of cells, with the use of devices called bioprinters. The latter can only function by receiving instructions from software. This paper focuses on some software-supported techniques that are key for bioprinting. It shows that a growing range of software packages has been used in bioprinting, a trend that is greatly fostered by open source software.In this evolution, the clinical potentialities of bioprinting come closer to their realization. At the same time, however, uncertainties emerge, related to issues such as data protection, use of biological samples, and others. The growing use of open source software complexifies the scenario, because it leads to a multiplication of actors directly or indirectly involved in the technology’s development, making it difficult to trace liabilities and damages.As no national regulation has been produced to tackle such uncertainties, they have been (provisionally and precariously) addressed in the licenses of software packages. In the years to come, as clinical products eventually spring from bioprinting research, more robust governance schemes will have to emerge in which risks and liabilities are dealt with more carefully by different players. Moreover, regulations will have to address the practice of combining different software packages in the same bioprinting process, as well as the growing globalization of bioprinting research and commercial exploration.
AUTHOR Park, Wonbin and Gao, Ge and Cho, Dong-Woo
Title Tissue-Specific Decellularized Extracellular Matrix Bioinks for Musculoskeletal Tissue Regeneration and Modeling Using 3D Bioprinting Technology [Abstract]
Year 2021
Journal/Proceedings International Journal of Molecular Sciences
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The musculoskeletal system is a vital body system that protects internal organs, supports locomotion, and maintains homeostatic function. Unfortunately, musculoskeletal disorders are the leading cause of disability worldwide. Although implant surgeries using autografts, allografts, and xenografts have been conducted, several adverse effects, including donor site morbidity and immunoreaction, exist. To overcome these limitations, various biomedical engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissue. In this review, the leading edge of musculoskeletal tissue engineering using 3D bioprinting technology and musculoskeletal tissue-derived decellularized extracellular matrix bioink is described. In particular, studies on in vivo regeneration and in vitro modeling of musculoskeletal tissue have been focused on. Lastly, the current breakthroughs, limitations, and future perspectives are described.
AUTHOR Iria Seoane-Viaño and Sarah J. Trenfield and Abdul W. Basit and Alvaro Goyanes
Title Translating 3D printed pharmaceuticals: From hype to real-world clinical applications [Abstract]
Year 2021
Journal/Proceedings Advanced Drug Delivery Reviews
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Three-dimensional (3D) printing is a revolutionary technology that is disrupting pharmaceutical development by enabling the production of personalised printlets (3D printed drug products) on demand. By creating small batches of dose flexible medicines, this versatile technology offers significant advantages for clinical practice and drug development, namely the ability to personalise medicines to individual patient needs, as well as expedite drug development timelines within preclinical studies through to first-in-human (FIH) and Phase I/II clinical trials. Despite the widely demonstrated benefits of 3D printing pharmaceuticals, the clinical potential of the technology is yet to be realised. In this timely review, we provide an overview of the latest cutting-edge investigations in 3D printing pharmaceuticals in the pre-clinical and clinical arena and offer a forward-looking approach towards strategies to further aid the translation of 3D printing into the clinic.
AUTHOR Lagatuz, M. and Vyas, R. J. and Predovic, M. and Lim, S. and Jacobs, N. and Martinho, M. and Valizadegan, H. and Kao, D. and Oza, N. and Theriot, C. A. and Zanello, S. B. and Taibbi, G. and Vizzeri, G. and Dupont, M. and Grant, M. B. and Lindner, D. J. and Reinecker, H.-C. and Pinhas, A. and Chui, T. Y. and Rosen, R. B. and Moldovan, N. and Vickerman, M. B. and Radhakrishnan, K. and Parsons-Wingerter, P.
Title Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis [Abstract]
Year 2021
Journal/Proceedings J Vasc Res
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The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.
AUTHOR Devillard, Chloé D. and Marquette, Christophe A.
Title Vascular Tissue Engineering: Challenges and Requirements for an Ideal Large Scale Blood Vessel [Abstract]
Year 2021
Journal/Proceedings Frontiers in Bioengineering and Biotechnology
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Since the emergence of regenerative medicine and tissue engineering more than half a century ago, one obstacle has persisted: the in vitro creation of large-scale vascular tissue (>1 cm3) to meet the clinical needs of viable tissue grafts but also for biological research applications. Considerable advancements in biofabrication have been made since Weinberg and Bell, in 1986, created the first blood vessel from collagen, endothelial cells, smooth muscle cells and fibroblasts. The synergistic combination of advances in fabrication methods, availability of cell source, biomaterials formulation and vascular tissue development, promises new strategies for the creation of autologous blood vessels, recapitulating biological functions, structural functions, but also the mechanical functions of a native blood vessel. In this review, the main technological advancements in bio-fabrication are discussed with a particular highlights on 3D bioprinting technologies. The choice of the main biomaterials and cell sources, the use of dynamic maturation systems such as bioreactors and the associated clinical trials will be detailed. The remaining challenges in this complex engineering field will finally be discussed.
AUTHOR Jhinuk Rahman and Julian Quodbach
Title Versatility on demand – The case for semi-solid micro-extrusion in pharmaceutics [Abstract]
Year 2021
Journal/Proceedings Advanced Drug Delivery Reviews
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Since additive manufacturing of pharmaceuticals has been introduced as viable method to produce individualized drug delivery systems with complex geometries and release profiles, semi-solid micro-extrusion has shown to be uniquely beneficial. Easy incorporation of actives, room-temperature processability and avoidance of cross-contamination by using disposables are some of the advantages that led many researchers to focus their work on this technology in the last few years. First acceptability and in-vivo studies have brought it closer towards implementation in decentralized settings. This review covers recently established process models in light of viscosity and printability discussions to help develop high quality printed medicines. Quality defining formulation and process parameters to characterize the various developed dosage forms are presented before critically discussing the role of semi-solid micro-extrusion in the future of personalized drug delivery systems. Remaining challenges regarding regulatory guidance and quality assurance that pose the last hurdle for large scale and commercial manufacturing are addressed.
AUTHOR Cui, Xiaolin and Li, Jun and Hartanto, Yusak and Durham, Mitchell and Tang, Junnan and Zhang, Hu and Hooper, Gary and Lim, Khoon and Woodfield, Tim
Title Advances in Extrusion 3D Bioprinting: A Focus on Multicomponent Hydrogel-Based Bioinks [Abstract]
Year 2020
Journal/Proceedings Advanced Healthcare Materials
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Abstract 3D bioprinting involves the combination of 3D printing technologies with cells, growth factors and biomaterials, and has been considered as one of the most advanced tools for tissue engineering and regenerative medicine (TERM). However, despite multiple breakthroughs, it is evident that numerous challenges need to be overcome before 3D bioprinting will eventually become a clinical solution for a variety of TERM applications. To produce a 3D structure that is biologically functional, cell-laden bioinks must be optimized to meet certain key characteristics including rheological properties, physico-mechanical properties, and biofunctionality; a difficult task for a single component bioink especially for extrusion based bioprinting. As such, more recent research has been centred on multicomponent bioinks consisting of a combination of two or more biomaterials to improve printability, shape fidelity and biofunctionality. In this article, multicomponent hydrogel-based bioink systems are systemically reviewed based on the inherent nature of the bioink (natural or synthetic hydrogels), including the most current examples demonstrating properties and advances in application of multicomponent bioinks, specifically for extrusion based 3D bioprinting. This review article will assist researchers in the field in identifying the most suitable bioink based on their requirements, as well as pinpointing current unmet challenges in the field.
AUTHOR Sohrabi, Somayeh and kassir, Nour and Keshavarz Moraveji, Mostafa
Title Droplet microfluidics: fundamentals and its advanced applications [Abstract]
Year 2020
Journal/Proceedings RSC Advances
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Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors{,} resulting in decreased reaction times. This{,} coupled with the precise generation and repeatability of droplet operations{,} has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as micro-reactors ranging from the nano- to femtoliter (10−15 liters) range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. For this{,} in the following article we will focus on the various droplet operations{,} as well as the numerous applications of the system and its future in many advanced scientific fields. Due to advantages of droplet-based systems{,} this technology has the potential to offer solutions to today{'}s biomedical engineering challenges for advanced diagnostics and therapeutics.
AUTHOR Rafiee, Mohammad and Farahani, Rouhollah D. and Therriault, Daniel
Title Multi-Material 3D and 4D Printing: A Survey [Abstract]
Year 2020
Journal/Proceedings Advanced Science
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Abstract Recent advances in multi-material 3D and 4D printing (time as the fourth dimension) show that the technology has the potential to extend the design space beyond complex geometries. The potential of these additive manufacturing (AM) technologies allows for functional inclusion in a low-cost single-step manufacturing process. Different composite materials and various AM technologies can be used and combined to create customized multi-functional objects to suit many needs. In this work, several types of 3D and 4D printing technologies are compared and the advantages and disadvantages of each technology are discussed. The various features and applications of 3D and 4D printing technologies used in the fabrication of multi-material objects are reviewed. Finally, new avenues for the development of multi-material 3D and 4D printed objects are proposed, which reflect the current deficiencies and future opportunities for inclusion by AM.
AUTHOR Chen, Grona and Xu, Yihua and Chi Lip Kwok, Philip and Kang, Lifeng
Title Pharmaceutical Applications of 3D Printing [Abstract]
Year 2020
Journal/Proceedings Additive Manufacturing
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Although 3D printing (3DP) has long been an integral part of industries such as aviation and automotive, its use in healthcare, especially the pharmaceutical industry, is relatively new and currently receiving close attention. At the beginning of 2018, we reviewed the applications of 3DP for drug delivery and drug testing [1]. Due to the rapid development of this field, it is necessary to summarize the latest development in this field after 2 years. In this article, we reviewed the three major areas in pharmaceutical applications. First, drug delivery system is the most studied subject, including controlled release, polypills, gastrofloating, orodispersibles and microneedles. Second, 3DP also helped the development of pharmaceutical devices, including pharmacy dispensing aids and drug eluting devices. Lastly, we reviewed the pharmaceutical models for drug testing, covering acellular and cellular models. We also summarized the materials used in the mentioned articles and their regulatory status for pharmaceutical applications to provide references for future research.
AUTHOR Bedell, Matthew L. and Navara, Adam M. and Du, Yingying and Zhang, Shengmin and Mikos, Antonios G.
Title Polymeric Systems for Bioprinting [Abstract]
Year 2020
Journal/Proceedings Chemical Reviews
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Bioprinting is rapidly being adopted as a major method for fabricating tissue engineering constructs. Through the precise deposition of cell- and bioactive molecule-laden materials, bioprinting offers researchers a means to create biological constructs with enhanced spatial complexity that more closely mimics native tissue. The vast majority of materials used in bioprinting have been polymers due to their suitability toward resembling the cellular environment and the variety of methods available to process polymeric systems in ambient or relatively mild chemical and environmental conditions. In this review, we will discuss in detail the wide variety of natural and synthetic polymers that have been employed as inks in bioprinting. We will review recent bioprinting innovations, such as increasing architectural complexity and cell viability in heterogeneous tissue constructs, which allow for the investigation of biological questions that could not be addressed before. We will also survey nascent fields of study that promise to further advance the development of novel biofabrication technologies in the field, such as 4D bioprinting and the inclusion of nanomaterials. To conclude, we will examine some of the necessary steps that must take place to bring this technology to commercial markets and facilitate its use in clinical therapies. Bioprinting is rapidly being adopted as a major method for fabricating tissue engineering constructs. Through the precise deposition of cell- and bioactive molecule-laden materials, bioprinting offers researchers a means to create biological constructs with enhanced spatial complexity that more closely mimics native tissue. The vast majority of materials used in bioprinting have been polymers due to their suitability toward resembling the cellular environment and the variety of methods available to process polymeric systems in ambient or relatively mild chemical and environmental conditions. In this review, we will discuss in detail the wide variety of natural and synthetic polymers that have been employed as inks in bioprinting. We will review recent bioprinting innovations, such as increasing architectural complexity and cell viability in heterogeneous tissue constructs, which allow for the investigation of biological questions that could not be addressed before. We will also survey nascent fields of study that promise to further advance the development of novel biofabrication technologies in the field, such as 4D bioprinting and the inclusion of nanomaterials. To conclude, we will examine some of the necessary steps that must take place to bring this technology to commercial markets and facilitate its use in clinical therapies.
AUTHOR Schwab, Andrea and Levato, Riccardo and D’Este, Matteo and Piluso, Susanna and Eglin, David and Malda, Jos
Title Printability and Shape Fidelity of Bioinks in 3D Bioprinting [Abstract]
Year 2020
Journal/Proceedings Chemical Reviews
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Three-dimensional bioprinting uses additive manufacturing techniques for the automated fabrication of hierarchically organized living constructs. The building blocks are often hydrogel-based bioinks, which need to be printed into structures with high shape fidelity to the intended computer-aided design. For optimal cell performance, relatively soft and printable inks are preferred, although these undergo significant deformation during the printing process, which may impair shape fidelity. While the concept of good or poor printability seems rather intuitive, its quantitative definition lacks consensus and depends on multiple rheological and chemical parameters of the ink. This review discusses qualitative and quantitative methodologies to evaluate printability of bioinks for extrusion- and lithography-based bioprinting. The physicochemical parameters influencing shape fidelity are discussed, together with their importance in establishing new models, predictive tools and printing methods that are deemed instrumental for the design of next-generation bioinks, and for reproducible comparison of their structural performance. Three-dimensional bioprinting uses additive manufacturing techniques for the automated fabrication of hierarchically organized living constructs. The building blocks are often hydrogel-based bioinks, which need to be printed into structures with high shape fidelity to the intended computer-aided design. For optimal cell performance, relatively soft and printable inks are preferred, although these undergo significant deformation during the printing process, which may impair shape fidelity. While the concept of good or poor printability seems rather intuitive, its quantitative definition lacks consensus and depends on multiple rheological and chemical parameters of the ink. This review discusses qualitative and quantitative methodologies to evaluate printability of bioinks for extrusion- and lithography-based bioprinting. The physicochemical parameters influencing shape fidelity are discussed, together with their importance in establishing new models, predictive tools and printing methods that are deemed instrumental for the design of next-generation bioinks, and for reproducible comparison of their structural performance.
AUTHOR Zhang, Xihui and Jiang, Tianyan and Chen, Dandan and Wang, Qi and Zhang, Leshuai W.
Title Three-dimensional liver models: state of the art and their application for hepatotoxicity evaluation [Abstract]
Year 2020
Journal/Proceedings Critical Reviews in Toxicology
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Abstract
AbstractWhile alternative methods for toxicity testing using re-constructed human skin and cornea have been written into guidelines and adopted by regulatory authorities, three-dimensional (3D) liver models are currently applied in the industrial settings for hepatotoxicity screening and prediction. These 3D liver models can recapitulate the architecture, functionality and toxicity response of the native liver, demonstrated by a set of related hallmarks. In this comprehensive review, non-scaffold and scaffold-based methods available for 3D liver model formation are introduced, with an emphasis on their advantages and drawbacks. We then focus on the characteristics of primary human hepatocytes, stem cell derived hepatocyte like cells, and immortalized hepatic cell lines as cell resources for model reconstruction. Primary hepatocytes are generally regarded to be superior to other cell types due to their comparable metabolic profiles to the native liver. Additionally, the application of 3D liver models (mostly liver spheroids) on the evaluation of drug induced liver injury and chronic liver diseases (steatosis, cirrhosis, cholestasis), as well as the potential of nanomaterials to introduce hepatotoxicity are summarized. Finally, the global 3D cell market from 3D liver model manufacturing to the contract service of in vitro hepatotoxicity testing using the models is extensively explored. However, 3D liver models face cultural and regulatory barriers in different countries, and therefore the business development of 3D liver models is not easy. Toxicologists, material scientists, engineers should work together to develop, validate and apply 3D liver models for hepatotoxicity testing under the support from industrial organizations and governmental agencies.
AUTHOR Li, J. and Liu, X. and Crook, J. M. and Wallace, G. G.
Title 3D graphene-containing structures for tissue engineering [Abstract]
Year 2019
Journal/Proceedings Materials Today Chemistry
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Abstract
Graphene and its derivatives have been extensively explored in various fields and have shown great promise toward energy harvesting, environmental protection, and health care. 3D graphene-containing structures (3DGCSs) are especially endowed with useable features relating to physicochemical properties within the hierarchical architectures. Thus, 3DGCSs are increasingly being applied for tissue engineering because of their supportability of human cells and functionalization potential. This review focuses on recent progress in tissue engineering utilizing 3DGCSs, providing insights into fabrication, application, and constraints in bionic research.
AUTHOR Mehrotra, Shreya and Moses, Joseph Christakiran and Bandyopadhyay, Ashutosh and Mandal, Biman B.
Title 3D Printing/Bioprinting Based Tailoring of in Vitro Tissue Models: Recent Advances and Challenges [Abstract]
Year 2019
Journal/Proceedings ACS Applied Bio Materials
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DOI/URL DOI
Abstract
Prodigious progress in the past decade has pronounced 3D printing as one of the most promising technique for assembling biological materials in a complex layout that mimics native human tissues. With the advent of technology, several improvements in printing techniques have facilitated the development of intricate strategies and designs that were imaginably distant due to the conventional top-down approaches. Most of these advanced strategies generally follow a thorough coordination and an elaborate biomimetic blueprint due to which it is now possible to fabricate in vitro tissue models with ease. However, much remains to be accomplished at several forefronts for utilizing this technology to its full potential. With several printing strategies at the lead, it has now become essential to systematically analyze and learn from several endeavors such that shortcomings can be understood and future efforts can be made toward negating them. Taking account of all the recent tissue specific developments in this field, this review serves as a framework for bringing together in discussion several strategies and constraints in developing small scaled in vitro tissues. Highlighting the growing popularity of the organ and body on chip platforms and their easy scale up using 3D printing, latest advancements, and the challenges in this field are also discussed. Prodigious progress in the past decade has pronounced 3D printing as one of the most promising technique for assembling biological materials in a complex layout that mimics native human tissues. With the advent of technology, several improvements in printing techniques have facilitated the development of intricate strategies and designs that were imaginably distant due to the conventional top-down approaches. Most of these advanced strategies generally follow a thorough coordination and an elaborate biomimetic blueprint due to which it is now possible to fabricate in vitro tissue models with ease. However, much remains to be accomplished at several forefronts for utilizing this technology to its full potential. With several printing strategies at the lead, it has now become essential to systematically analyze and learn from several endeavors such that shortcomings can be understood and future efforts can be made toward negating them. Taking account of all the recent tissue specific developments in this field, this review serves as a framework for bringing together in discussion several strategies and constraints in developing small scaled in vitro tissues. Highlighting the growing popularity of the organ and body on chip platforms and their easy scale up using 3D printing, latest advancements, and the challenges in this field are also discussed.
AUTHOR Kjar, Andrew and Huang, Yu
Title Application of Micro-Scale 3D Printing in Pharmaceutics [Abstract]
Year 2019
Journal/Proceedings Pharmaceutics
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Abstract
3D printing, as one of the most rapidly-evolving fabrication technologies, has released a cascade of innovation in the last two decades. In the pharmaceutical field, the integration of 3D printing technology has offered unique advantages, especially at the micro-scale. When printed at a micro-scale, materials and devices can provide nuanced solutions to controlled release, minimally invasive delivery, high-precision targeting, biomimetic models for drug discovery and development, and future opportunities for personalized medicine. This review aims to cover the recent advances in this area. First, the 3D printing techniques are introduced with respect to the technical parameters and features that are uniquely related to each stage of pharmaceutical development. Then specific micro-sized pharmaceutical applications of 3D printing are summarized and grouped according to the provided benefits. Both advantages and challenges are discussed for each application. We believe that these technologies provide compelling future solutions for modern medicine, while challenges remain for scale-up and regulatory approval.
AUTHOR Yilmaz, B. and Tahmasebifar, A. and Baran, E. T.
Title Bioprinting Technologies in Tissue Engineering
Year 2019
Journal/Proceedings Advances in Biochemical Engineering/Biotechnology
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AUTHOR Valot, Laurine and Martinez, Jean and Mehdi, Ahmad and Subra, Gilles
Title Chemical insights into bioinks for 3D printing [Abstract]
Year 2019
Journal/Proceedings Chemical Society Reviews
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Abstract
3D printing has triggered the acceleration of numerous research areas in health sciences{,} which traditionally used cells as starting materials{,} in particular tissue engineering{,} regenerative medicine and also in the design of more relevant bioassays for drug discovery and development. While cells can be successfully printed in 2D layers without the help of any supporting biomaterial{,} the obtainment of more complex 3D architectures requires a specific bioink{,} i.e. a material in which the cells are embedded during and after the printing process helping to support them while they are arranged in superimposed layers. The bioink plays a critical role in bioprinting: first{,} it must be adapted to the 3D printing technology; then{,} it must fulfil the physicochemical and mechanical characteristics of the target construct (e.g. stiffness{,} elasticity{,} robustness{,} transparency); finally it should guarantee cell viability and eventually induce a desired behaviour. This review focuses on the nature of bioink components of natural or synthetic origin{,} and highlights the chemistry required for the establishment of the 3D network in conditions compatible with the selected 3D printing technique and cell survival.
AUTHOR Loai, Sadi and Kingston, Benjamin R. and Wang, Zongjie and Philpott, David N. and Tao, Mingyang and Cheng, Hai-Ling Margaret
Title Clinical Perspectives on 3D Bioprinting Paradigms for Regenerative Medicine
Year 2019
Journal/Proceedings Regenerative Medicine Frontiers
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AUTHOR Marques, C. F. and Diogo, G. S. and Pina, S. and Oliveira, J. M. and Silva, T. H. and Reis, R. L.
Title Collagen-based bioinks for hard tissue engineering applications: a comprehensive review [Abstract]
Year 2019
Journal/Proceedings Journal of Materials Science: Materials in Medicine
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DOI/URL DOI
Abstract
In the last few years, additive manufacturing (AM) has been gaining great interest in the fabrication of complex structures for soft-to-hard tissues regeneration, with tailored porosity, and boosted structural, mechanical, and biological properties. 3D printing is one of the most known AM techniques in the field of biofabrication of tissues and organs. This technique opened up opportunities over the conventional ones, with the capability of creating replicable, customized, and functional structures that can ultimately promote effectively different tissues regeneration. The uppermost component of 3D printing is the bioink, i.e. a mixture of biomaterials that can also been laden with different cell types, and bioactive molecules. Important factors of the fabrication process include printing fidelity, stability, time, shear-thinning properties, mechanical strength and elasticity, as well as cell encapsulation and cell-compatible conditions. Collagen-based materials have been recognized as a promising choice to accomplish an ideal mimetic bioink for regeneration of several tissues with high cell-activating properties. This review presents the state-of-art of the current achievements on 3D printing using collagen-based materials for hard tissue engineering, particularly on the development of scaffolds for bone and cartilage repair/regeneration. The ultimate aim is to shed light on the requirements to successfully print collagen-based inks and the most relevant properties exhibited by the so fabricated scaffolds. In this regard, the adequate bioprinting parameters are addressed, as well as the main materials properties, namely physicochemical and mechanical properties, cell compatibility and commercial availability, covering hydrogels, microcarriers and decellularized matrix components. Furthermore, the fabrication of these bioinks with and without cells used in inkjet printing, laser-assisted printing, and direct in writing technologies are also overviewed. Finally, some future perspectives of novel bioinks are given.
AUTHOR Angelopoulos, Ioannis and Allenby, Mark C. and Lim, Mayasari and Zamorano, Mauricio
Title Engineering inkjet bioprinting processes toward translational therapies [Abstract]
Year 2019
Journal/Proceedings Biotechnology and Bioengineering
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Abstract
Abstract Bioprinting is the assembly of three-dimensional (3D) tissue constructs by layering cell-laden biomaterials using additive manufacturing techniques, offering great potential for tissue engineering and regenerative medicine. Such a process can be performed with high resolution and control by personalized or commercially available inkjet printers. However, bioprinting's clinical translation is significantly limited due to process engineering challenges. Upstream challenges include synthesis, cellular incorporation, and functionalization of “bioinks,” and extrusion of print geometries. Downstream challenges address sterilization, culture, implantation, and degradation. In the long run, bioinks must provide a microenvironment to support cell growth, development, and maturation and must interact and integrate with the surrounding tissues after implantation. Additionally, a robust, scaleable manufacturing process must pass regulatory scrutiny from regulatory bodies such as U.S. Food and Drug Administration, European Medicines Agency, or Australian Therapeutic Goods Administration for bioprinting to have a real clinical impact. In this review, recent advances in inkjet-based 3D bioprinting will be presented, emphasizing on biomaterials available, their properties, and the process to generate bioprinted constructs with application in medicine. Current challenges and the future path of bioprinting and bioinks will be addressed, with emphasis in mass production aspects and the regulatory framework bioink-based products must comply to translate this technology from the bench to the clinic.
AUTHOR Jiang, Tao and Munguía López, Jose and Flores-Torres, Salvador and Kort-Mascort, Jacqueline and Kinsella, Joseph
Title Extrusion bioprinting of soft materials: An emerging technique for biological model fabrication
Year 2019
Journal/Proceedings Applied Physics Reviews
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AUTHOR Geetha Bai, Renu and Muthoosamy, Kasturi and Manickam, Sivakumar and Hilal-Alnaqbi, Ali
Title Graphene-based 3D scaffolds in tissue engineering: fabrication, applications, and future scope in liver tissue engineering [Abstract]
Year 2019
Journal/Proceedings International journal of nanomedicine
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Abstract
Tissue engineering embraces the potential of recreating and replacing defective body parts by advancements in the medical field. Being a biocompatible nanomaterial with outstanding physical, chemical, optical, and biological properties, graphene-based materials were successfully employed in creating the perfect scaffold for a range of organs, starting from the skin through to the brain. Investigations on 2D and 3D tissue culture scaffolds incorporated with graphene or its derivatives have revealed the capability of this carbon material in mimicking in vivo environment. The porous morphology, great surface area, selective permeability of gases, excellent mechanical strength, good thermal and electrical conductivity, good optical properties, and biodegradability enable graphene materials to be the best component for scaffold engineering. Along with the apt microenvironment, this material was found to be efficient in differentiating stem cells into specific cell types. Furthermore, the scope of graphene nanomaterials in liver tissue engineering as a promising biomaterial is also discussed. This review critically looks into the unlimited potential of graphene-based nanomaterials in future tissue engineering and regenerative therapy.
AUTHOR Romanazzo, Sara and Nemec, Stephanie and Roohani, Iman
Title iPSC Bioprinting: Where are We at? [Abstract]
Year 2019
Journal/Proceedings Materials
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Abstract
Here, we present a concise review of current 3D bioprinting technologies applied to induced pluripotent stem cells (iPSC). iPSC have recently received a great deal of attention from the scientific and clinical communities for their unique properties, which include abundant adult cell sources, ability to indefinitely self-renew and differentiate into any tissue of the body. Bioprinting of iPSC and iPSC derived cells combined with natural or synthetic biomaterials to fabricate tissue mimicked constructs, has emerged as a technology that might revolutionize regenerative medicine and patient-specific treatment. This review covers the advantages and disadvantages of bioprinting techniques, influence of bioprinting parameters and printing condition on cell viability, and commonly used iPSC sources, and bioinks. A clear distinction is made for bioprinting techniques used for iPSC at their undifferentiated stage or when used as adult stem cells or terminally differentiated cells. This review presents state of the art data obtained from major searching engines, including Pubmed/MEDLINE, Google Scholar, and Scopus, concerning iPSC generation, undifferentiated iPSC, iPSC bioprinting, bioprinting techniques, cartilage, bone, heart, neural tissue, skin, and hepatic tissue cells derived from iPSC.
AUTHOR Fenton, Owen S. and Paolini, Marion and Andresen, Jason L. and Müller, Florence J. and Langer, Robert
Title Outlooks on Three-Dimensional Printing for Ocular Biomaterials Research [Abstract]
Year 2019
Journal/Proceedings Journal of Ocular Pharmacology and Therapeutics
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Abstract
Abstract Given its potential for high-resolution, customizable, and waste-free fabrication of medical devices and in vitro biological models, 3-dimensional (3D) bioprinting has broad utility within the biomaterials field. Indeed, 3D bioprinting has to date been successfully used for the development of drug delivery systems, the recapitulation of hard biological tissues, and the fabrication of cellularized organ and tissue-mimics, among other applications. In this study, we highlight convergent efforts within engineering, cell biology, soft matter, and chemistry in an overview of the 3D bioprinting field, and we then conclude our work with outlooks toward the application of 3D bioprinting for ocular research in vitro and in vivo.
AUTHOR Prendergast, Margaret E. and Burdick, Jason A.
Title Recent Advances in Enabling Technologies in 3D Printing for Precision Medicine [Abstract]
Year 2019
Journal/Proceedings Advanced Materials
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Abstract
Abstract Advances in areas such as data analytics, genomics, and imaging have revealed individual patient complexities and exposed the inherent limitations of generic therapies for patient treatment. These observations have also fueled the development of precision medicine approaches, where therapies are tailored for the individual rather than the broad patient population. 3D printing is a field that intersects with precision medicine through the design of precision implants with patient-directed shapes, structures, and materials or for the development of patient-specific in vitro models that can be used for screening precision therapeutics. Toward their success, advances in 3D printing and biofabrication technologies are needed with enhanced resolution, complexity, reproducibility, and speed and that encompass a broad range of cells and materials. The overall goal of this progress report is to highlight recent advances in 3D printing technologies that are helping to enable advances important in precision medicine.
AUTHOR Costa, Pedro F.
Title Translating Biofabrication to the Market [Abstract]
Year 2019
Journal/Proceedings Trends in Biotechnology
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Abstract
Biofabrication holds great potential to revolutionize important industries in the health, food, and textile sectors, but its translation to market is still challenging. I analyze the current state of innovation and commercialization in biofabrication and try to assess its limitations, strengths, and future progress.
AUTHOR Lim, Seng Han and Kathuria, Himanshu and Tan, Justin Jia Yao and Kang, Lifeng
Title 3D printed drug delivery and testing systems — a passing fad or the future? [Abstract]
Year 2018
Journal/Proceedings Advanced Drug Delivery Reviews
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Abstract
The US Food and Drug Administration approval of the first 3D printed tablet in 2015 has ignited growing interest in 3D printing, or additive manufacturing (AM), for drug delivery and testing systems. Beyond just a novel method for rapid prototyping, AM provides key advantages over traditional manufacturing of drug delivery and testing systems. These includes the ability to fabricate complex geometries to achieve variable drug release kinetics; ease of personalising pharmacotherapy for patient and lowering the cost for fabricating personalised dosages. Furthermore, AM allows fabrication of complex and micron-sized tissue scaffolds and models for drug testing systems that closely resemble in vivo conditions. However, there are several limitations such as regulatory concerns that may impede the progression to market. Here, we provide an overview of the advantages of AM drug delivery and testing, as compared to traditional manufacturing techniques. Also, we discuss the key challenges and future directions for AM enabled pharmaceutical applications.
AUTHOR Rayate, Amol and Jain, Prashant K.
Title A Review on 4D Printing Material Composites and Their Applications [Abstract]
Year 2018
Journal/Proceedings Materials Today: Proceedings
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Abstract
4D printing is an extension of 3D printing in which stimuli-responsive active smart materials are used to produce the static structure. This static structure then converts into another structure when it is exposed to the stimulus. Type of stimulus may be light, heat, pH, water, magnetic field etc. depending upon the material selected for 3D printing. In recent advances, these dynamic structures developed by 3D printing process are used for actuators, smart devices, aesthetic primitives, smart textiles, and also in biomedical applications. This paper is about the brief overview of the advanced materials for 4D printing and their applications.
AUTHOR Gungor-Ozkerim, P. Selcan and Inci, Ilyas and Zhang, Yu Shrike and Khademhosseini, Ali and Dokmeci, Mehmet Remzi
Title Bioinks for 3D bioprinting: an overview [Abstract]
Year 2018
Journal/Proceedings Biomaterials Science
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Abstract
Bioprinting is an emerging technology with various applications in making functional tissue constructs to replace injured or diseased tissues. It is a relatively new approach that provides high reproducibility and precise control over the fabricated constructs in an automated manner{,} potentially enabling high-throughput production. During the bioprinting process{,} a solution of a biomaterial or a mixture of several biomaterials in the hydrogel form{,} usually encapsulating the desired cell types{,} termed the bioink{,} is used for creating tissue constructs. This bioink can be cross-linked or stabilized during or immediately after bioprinting to generate the final shape{,} structure{,} and architecture of the designed construct. Bioinks may be made from natural or synthetic biomaterials alone{,} or a combination of the two as hybrid materials. In certain cases{,} cell aggregates without any additional biomaterials can also be adopted for use as a bioink for bioprinting processes. An ideal bioink should possess proper mechanical{,} rheological{,} and biological properties of the target tissues{,} which are essential to ensure correct functionality of the bioprinted tissues and organs. In this review{,} we provide an in-depth discussion of the different bioinks currently employed for bioprinting{,} and outline some future perspectives in their further development.
AUTHOR Monz{'o}n, Mario and Liu, Chaozong and Ajami, Sara and Oliveira, Miguel and Donate, Ricardo and Ribeiro, Viviana and Reis, Rui L.
Title Functionally graded additive manufacturing to achieve functionality specifications of osteochondral scaffolds
Year 2018
Journal/Proceedings Bio-Design and Manufacturing
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AUTHOR Gill, Elisabeth L. and Li, Xia and Birch, Mark A. and Huang, Yan Yan Shery
Title Multi-length scale bioprinting towards simulating microenvironmental cues [Abstract]
Year 2018
Journal/Proceedings Bio-Design and Manufacturing
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Abstract
It is envisaged that the creation of cellular environments at multiple length scales, that recapitulate in vivo bioactive and structural roles, may hold the key to creating functional, complex tissues in the laboratory. This review considers recent advances in biofabrication and bioprinting techniques across different length scales. Particular focus is placed on 3D printing of hydrogels and fabrication of biomaterial fibres that could extend the feature resolution and material functionality of soft tissue constructs. The outlook from this review discusses how one might create and simulate microenvironmental cues in vitro. A fabrication platform that integrates the competencies of different biofabrication technologies is proposed. Such a multi-process, multiscale fabrication strategy may ultimately translate engineering capability into an accessible life sciences toolkit, fulfilling its potential to deliver in vitro disease models and engineered tissue implants.
AUTHOR Chinga-Carrasco, Gary
Title Potential and Limitations of Nanocelluloses as Components in Biocomposite Inks for Three-Dimensional Bioprinting and for Biomedical Devices [Abstract]
Year 2018
Journal/Proceedings Biomacromolecules
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DOI/URL DOI
Abstract
Three-dimensional (3D) printing has rapidly emerged as a new technology with a wide range of applications that includes biomedicine. Some common 3D printing methods are based on the suitability of biopolymers to be extruded through a nozzle to construct a 3D structure layer by layer. Nanocelluloses with specific rheological characteristics are suitable components to form inks for 3D printing. This review considers various nanocelluloses that have been proposed for 3D printing with a focus on the potential advantages, limitations, and requirements when used for biomedical devices and when used in contact with the human body.
AUTHOR Li, Huijun and Tan, Cavin and Li, Lin
Title Review of 3D printable hydrogels and constructs [Abstract]
Year 2018
Journal/Proceedings Materials and Design
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Abstract
Three dimensional (3D) bioprinting technologies with appropriate bioinks are potentially able to fabricate artificial tissues or organs with precise control. A bioink is a mixture of biomaterial and living cells, which is a biomaterial for bioprinting. Hydrogels are the most appealing candidates of biomaterials because they have many similar features of the natural extracellular matrix and could also provide a highly hydrated environment for cell proliferation. In this field of bio-fabrication, particularly in bioprinting, the lack of suitable hydrogels remains a major challenge. Thus, choosing appropriate hydrogels for bioprinting is the key to print self-supporting 3D constructs. Most importantly, the considerations regarding the bioinks and the obtained constructs should be made clear. This review aims to provide the specific considerations regarding the important properties of a potential bioink and the generated 3D construct, including rheological, interfacial, structural, biological, and degradation properties, which are crucial for printing of complex and functional 3D structures. Among all of the above considerations, interfacial bonding is one of the important considerations of successfully obtaining a 3D structure. Unfortunately, it is rarely mentioned in the prior literature. This review also points out, for the first time, the characterization of a potential bioink from a rheological point of view. To provide readers with an understanding of the background, the review will first present current technologies for bioprinting and their limitations. Following this will be a summary and discussion of some frequently used hydrogels for bioprinting, and their respective limitations as well. The readers will be informed on the current limitations and achievements in 3D bioprinting. This review ultimately intends to help researchers to select or develop suitable bioinks for successfully bioprinting 3D constructs.
AUTHOR Gleadall, Andrew and Visscher, Dafydd and Yang, Jing and Thomas, Daniel and Segal, Joel
Title Review of additive manufactured tissue engineering scaffolds: relationship between geometry and performance [Abstract]
Year 2018
Journal/Proceedings Burns and Trauma
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DOI/URL DOI
Abstract
Material extrusion additive manufacturing has rapidly grown in use for tissue engineering research since its adoption in the year 2000. It has enabled researchers to produce scaffolds with intricate porous geometries that were not feasible with traditional manufacturing processes. Researchers can control the structural geometry through a wide range of customisable printing parameters and design choices including material, print path, temperature, and many other process parameters. Currently, the impact of these choices is not fully understood. This review focuses on how the position and orientation of extruded filaments, which sometimes referred to as the print path, lay-down pattern, or simply ``scaffold design'', affect scaffold properties and biological performance. By analysing trends across multiple studies, new understanding was developed on how filament position affects mechanical properties. Biological performance was also found to be affected by filament position, but a lack of consensus between studies indicates a need for further research and understanding. In most research studies, scaffold design was dictated by capabilities of additive manufacturing software rather than free-form design of structural geometry optimised for biological requirements. There is scope for much greater application of engineering innovation to additive manufacture novel geometries. To achieve this, better understanding of biological requirements is needed to enable the effective specification of ideal scaffold geometries.
AUTHOR Raghunath, Michael and Rimann, Markus and Kopanska, Katarzyna and Laternser, Sandra
Title TEDD Annual Meeting with 3D Bioprinting Workshop [Abstract]
Year 2018
Journal/Proceedings CHIMIA
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Abstract
Bioprinting is the technology of choice for realizing functional tissues such as vascular system, muscle, cartilage and bone. In the future, bioprinting will influence the way we engineer tissues and bring it to a new level of physiological relevance. That was the topic of the 2017 TEDD Annual Meeting at ZHAW Waedenswil on 8th and 9th November. In an exciting workshop, the two companies regenHU Ltd. and CELLINK gave us an insight into highly topical applications and collaborations in this domain.
AUTHOR Choudhury, Deepak and Anand, Shivesh and Win Naing, May
Title The Arrival of Commercial Bioprinters - Towards 3D Bioprinting Revolution!
Year 2018
Journal/Proceedings International Journal of Bioprinting
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DOI/URL DOI
AUTHOR Huang, Ying and Zhang, Xiao-Fei and Gao, Guifang and Yonezawa, Tomo and Cui, Xiaofeng
Title 3D bioprinting and the current applications in tissue engineering [Abstract]
Year 2017
Journal/Proceedings Biotechnology Journal
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DOI/URL DOI
Abstract
Bioprinting as an enabling technology for tissue engineering possesses the promises to fabricate highly mimicked tissue or organs with digital control. As one of the biofabrication approaches, bioprinting has the advantages of high throughput and precise control of both scaffold and cells. Therefore, this technology is not only ideal for translational medicine but also for basic research applications. Bioprinting has already been widely applied to construct functional tissues such as vasculature, muscle, cartilage, and bone. In this review, the authors introduce the most popular techniques currently applied in bioprinting, as well as the various bioprinting processes. In addition, the composition of bioink including scaffolds and cells are described. Furthermore, the most current applications in organ and tissue bioprinting are introduced. The authors also discuss the challenges we are currently facing and the great potential of bioprinting. This technology has the capacity not only in complex tissue structure fabrication based on the converted medical images, but also as an efficient tool for drug discovery and preclinical testing. One of the most promising future advances of bioprinting is to develop a standard medical device with the capacity of treating patients directly on the repairing site, which requires the development of automation and robotic technology, as well as our further understanding of biomaterials and stem cell biology to integrate various printing mechanisms for multi-phasic tissue engineering.
AUTHOR Peng, Weijie and Datta, Pallab and Ayan, Bugra and Ozbolat, Veli and Sosnoski, Donna and Ozbolat, Ibrahim T.
Title 3D bioprinting for drug discovery and development in pharmaceutics [Abstract]
Year 2017
Journal/Proceedings Acta Biomaterialia
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Abstract
Successful launch of a commercial drug requires significant investment of time and financial resources wherein late-stage failures become a reason for catastrophic failures in drug discovery. This calls for infusing constant innovations in technologies, which can give reliable prediction of efficacy, and more importantly, toxicology of the compound early in the drug discovery process before clinical trials. Though computational advances have resulted in more rationale in silico designing, in vitro experimental studies still require gaining industry confidence and improving in vitro-in vivo correlations. In this quest, due to their ability to mimic the spatial and chemical attributes of native tissues, three-dimensional (3D) tissue models have now proven to provide better results for drug screening compared to traditional two-dimensional (2D) models. However, in vitro fabrication of living tissues has remained a bottleneck in realizing the full potential of 3D models. Recent advances in bioprinting provide a valuable tool to fabricate biomimetic constructs, which can be applied in different stages of drug discovery research. This paper presents the first comprehensive review of bioprinting techniques applied for fabrication of 3D tissue models for pharmaceutical studies. A comparative evaluation of different bioprinting modalities is performed to assess the performance and ability of fabricating 3D tissue models for pharmaceutical use as the critical selection of bioprinting modalities indeed plays a crucial role in efficacy and toxicology testing of drugs and accelerates the drug development cycle. In addition, limitations with current tissue models are discussed thoroughly and future prospects of the role of bioprinting in pharmaceutics are provided to the reader. Present advances in tissue biofabrication have crucial role to play in aiding the pharmaceutical development process achieve its objectives. Advent of three-dimensional (3D) models, in particular, is viewed with immense interest by the community due to their ability to mimic in vivo hierarchical tissue architecture and heterogeneous composition. Successful realization of 3D models will not only provide greater in vitro-in vivo correlation compared to the two-dimensional (2D) models, but also eventually replace pre-clinical animal testing, which has their own shortcomings. Amongst all fabrication techniques, bioprinting- comprising all the different modalities (extrusion-, droplet- and laser-based bioprinting), is emerging as the most viable fabrication technique to create the biomimetic tissue constructs. Notwithstanding the interest in bioprinting by the pharmaceutical development researchers, it can be seen that there is a limited availability of comparative literature which can guide the proper selection of bioprinting processes and associated considerations, such as the bioink selection for a particular pharmaceutical study. Thus, this work emphasizes these aspects of bioprinting and presents them in perspective of differential requirements of different pharmaceutical studies like in vitro predictive toxicology, high-throughput screening, drug delivery and tissue-specific efficacies. Moreover, since bioprinting techniques are mostly applied in regenerative medicine and tissue engineering, a comparative analysis of similarities and differences are also expounded to help researchers make informed decisions based on contemporary literature.
AUTHOR Choi, Y. J. and Yi, H. G. and Kim, S. W. and Cho, D. W.
Title 3D Cell Printed Tissue Analogues: A New Platform for Theranostics [Abstract]
Year 2017
Journal/Proceedings Theranostics
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DOI/URL URL
Abstract
Stem cell theranostics has received much attention for noninvasively monitoring and tracing transplanted therapeutic stem cells through imaging agents and imaging modalities. Despite the excellent regenerative capability of stem cells, their efficacy has been limited due to low cellular retention, low survival rate, and low engraftment after implantation. Three-dimensional (3D) cell printing provides stem cells with the similar architecture and microenvironment of the native tissue and facilitates the generation of a 3D tissue-like construct that exhibits remarkable regenerative capacity and functionality as well as enhanced cell viability. Thus, 3D cell printing can overcome the current concerns of stem cell therapy by delivering the 3D construct to the damaged site. Despite the advantages of 3D cell printing, the in vivo and in vitro tracking and monitoring of the performance of 3D cell printed tissue in a noninvasive and real-time manner have not been thoroughly studied. In this review, we explore the recent progress in 3D cell technology and its applications. Finally, we investigate their potential limitations and suggest future perspectives on 3D cell printing and stem cell theranostics.
AUTHOR Sultan, Sahar and Siqueira, Gilberto and Zimmermann, Tanja and Mathew, Aji P.
Title 3D printing of nano-cellulosic biomaterials for medical applications [Abstract]
Year 2017
Journal/Proceedings Current Opinion in Biomedical Engineering
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DOI/URL URL DOI
Abstract
Abstract Nanoscaled versions of cellulose viz. cellulose nanofibers (CNF) or cellulose nanocrystals (CNC) isolated from natural resources are being used extensively since the past decade in the biomedical field e.g. for tissue engineering, implants, drug delivery systems, cardiovascular devices, and wound healing due to their remarkable mechanical, chemical and biocompatible properties. In the recent years, 3D printing of nanocellulose in combination with polymers is being studied as a viable route to future regenerative therapy. The printability of nanocellulose hydrogels owing to their shear thinning behavior and the possibility to support living cells allows 3D bioprinting using nanocellulose, a recent development which holds tremendous potential.
AUTHOR Charbe, Nitin B. and McCarron, Paul A. and Lane, Majella E. and Tambuwala, Murtaza M.
Title Application of three-dimensional printing for colon targeted drug delivery systems [Abstract]
Year 2017
Journal/Proceedings International Journal of Pharmaceutical Investigation
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DOI/URL URL
Abstract
Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.
AUTHOR Aljohani, Waeljumah and Ullah, Muhammad Wajid and Zhang, Xianglin and Yang, Guang
Title Bioprinting and its applications in tissue engineering and regenerative medicine [Abstract]
Year 2017
Journal/Proceedings International Journal of Biological Macromolecules
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Abstract
Abstract Bioprinting of three-dimensional constructs mimicking natural-like extracellular matrix has revolutionized biomedical technology. Bioprinting technology circumvents various discrepancies associated with current tissue engineering strategies by providing an automated and advanced platform to fabricate various biomaterials through precise deposition of cells and polymers in a premeditated fashion. However, few obstacles associated with development of 3D scaffolds including varied properties of polymers used and viability, controlled distribution, and vascularization, etc. of cells hinder bioprinting of complex structures. Therefore, extensive efforts have been made to explore the potential of various natural polymers (e.g. cellulose, gelatin, alginate, and chitosan, etc.) and synthetic polymers in bioprinting by tuning their printability and cross-linking features, mechanical and thermal properties, biocompatibility, and biodegradability, etc. This review describes the potential of these polymers to support adhesion and proliferation of viable cells to bioprint cell laden constructs, bone, cartilage, skin, and neural tissues, and blood vessels, etc. for various applications in tissue engineering and regenerative medicines. Further, it describes various challenges associated with current bioprinting technology and suggests possible solutions. Although at early stage of development, the potential benefits of bioprinting technology are quite clear and expected to open new gateways in biomedical, pharmaceutics and several other fields in near future.
AUTHOR Borovjagin, Anton V. and Ogle, Brenda M. and Berry, Joel L. and Zhang, Jianyi
Title From Microscale Devices to 3D Printing [Abstract]
Year 2017
Journal/Proceedings Circulation Research
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Abstract
Current strategies for engineering cardiovascular cells and tissues have yielded a variety of sophisticated tools for studying disease mechanisms, for development of drug therapies, and for fabrication of tissue equivalents that may have application in future clinical use. These efforts are motivated by the need to extend traditional 2-dimensional (2D) cell culture systems into 3D to more accurately replicate in vivo cell and tissue function of cardiovascular structures. Developments in microscale devices and bioprinted 3D tissues are beginning to supplant traditional 2D cell cultures and preclinical animal studies that have historically been the standard for drug and tissue development. These new approaches lend themselves to patient-specific diagnostics, therapeutics, and tissue regeneration. The emergence of these technologies also carries technical challenges to be met before traditional cell culture and animal testing become obsolete. Successful development and validation of 3D human tissue constructs will provide powerful new paradigms for more cost effective and timely translation of cardiovascular tissue equivalents.
AUTHOR Dalton, Paul D.
Title Melt electrowriting with additive manufacturing principles [Abstract]
Year 2017
Journal/Proceedings Current Opinion in Biomedical Engineering
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Abstract
Abstract The recent development of electrostatic writing (electrowriting) with molten jets provides an opportunity to tackle some significant challenges within tissue engineering. The process uses an applied voltage to generate a stable fluid jet with a predictable path, that is continuously deposited onto a collector. The fiber diameter is variable during the process, and is applicable to polymers with a history of clinical use. Melt electrowriting therefore has potential for clinical translation if the biological efficacy of the implant can be improved over existing gold standards. It provides a unique opportunity for laboratories to perform low-cost, high resolution, additive manufacturing research that is well positioned for clinical translation, using existing regulatory frameworks.
AUTHOR Ligon, Samuel Clark and Liska, Robert and Stampfl, Jürgen and Gurr, Matthias and Mülhaupt, Rolf
Title Polymers for 3D Printing and Customized Additive Manufacturing [Abstract]
Year 2017
Journal/Proceedings Chemical Reviews
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Abstract
Additive manufacturing (AM) alias 3D printing translates computer-aided design (CAD) virtual 3D models into physical objects. By digital slicing of CAD, 3D scan, or tomography data, AM builds objects layer by layer without the need for molds or machining. AM enables decentralized fabrication of customized objects on demand by exploiting digital information storage and retrieval via the Internet. The ongoing transition from rapid prototyping to rapid manufacturing prompts new challenges for mechanical engineers and materials scientists alike. Because polymers are by far the most utilized class of materials for AM, this Review focuses on polymer processing and the development of polymers and advanced polymer systems specifically for AM. AM techniques covered include vat photopolymerization (stereolithography), powder bed fusion (SLS), material and binder jetting (inkjet and aerosol 3D printing), sheet lamination (LOM), extrusion (FDM, 3D dispensing, 3D fiber deposition, and 3D plotting), and 3D bioprinting. The range of polymers used in AM encompasses thermoplastics, thermosets, elastomers, hydrogels, functional polymers, polymer blends, composites, and biological systems. Aspects of polymer design, additives, and processing parameters as they relate to enhancing build speed and improving accuracy, functionality, surface finish, stability, mechanical properties, and porosity are addressed. Selected applications demonstrate how polymer-based AM is being exploited in lightweight engineering, architecture, food processing, optics, energy technology, dentistry, drug delivery, and personalized medicine. Unparalleled by metals and ceramics, polymer-based AM plays a key role in the emerging AM of advanced multifunctional and multimaterial systems including living biological systems as well as life-like synthetic systems.
AUTHOR Gu, Bon Kang and Choi, Dong Jin and Park, Sang Jun and Kim, Min Sup and Kang, Chang Mo and Kim, Chun-Ho
Title 3-dimensional bioprinting for tissue engineering applications [Abstract]
Year 2016
Journal/Proceedings Biomaterials Research
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Abstract
The 3-dimensional (3D) printing technologies, referred to as additive manufacturing (AM) or rapid prototyping (RP), have acquired reputation over the past few years for art, architectural modeling, lightweight machines, and tissue engineering applications. Among these applications, tissue engineering field using 3D printing has attracted the attention from many researchers. 3D bioprinting has an advantage in the manufacture of a scaffold for tissue engineering applications, because of rapid-fabrication, high-precision, and customized-production, etc. In this review, we will introduce the principles and the current state of the 3D bioprinting methods. Focusing on some of studies that are being current application for biomedical and tissue engineering fields using printed 3D scaffolds.
AUTHOR Gudapati, Hemanth and Dey, Madhuri and Ozbolat, Ibrahim
Title A comprehensive review on droplet-based bioprinting: Past, present and future. [Abstract]
Year 2016
Journal/Proceedings Biomaterials
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Abstract
Droplet-based bioprinting (DBB) offers greater advantages due to its simplicity and agility with precise control on deposition of biologics including cells, growth factors, genes, drugs and biomaterials, and has been a prominent technology in the bioprinting community. Due to its immense versatility, DBB technology has been adopted by various application areas, including but not limited to, tissue engineering and regenerative medicine, transplantation and clinics, pharmaceutics and high-throughput screening, and cancer research. Despite the great benefits, the technology currently faces several challenges such as a narrow range of available bioink materials, bioprinting-induced cell damage at substantial levels, limited mechanical and structural integrity of bioprinted constructs, and restrictions on the size of constructs due to lack of vascularization and porosity. This paper presents a first-time review of DBB and comprehensively covers the existing DBB modalities including inkjet, electrohydrodynamic, acoustic, and micro-valve bioprinting. The recent notable studies are highlighted, the relevant bioink biomaterials and bioprinters are expounded, the application areas are presented, and the future prospects are provided to the reader.
AUTHOR Sears, Nick A. and Seshadri, Dhruv R. and Dhavalikar, Prachi S. and Cosgriff-Hernandez, Elizabeth
Title A Review of Three-Dimensional Printing in Tissue Engineering [Abstract]
Year 2016
Journal/Proceedings Tissue Engineering Part B: Reviews
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Abstract
Recent advances in three-dimensional (3D) printing technologies have led to a rapid expansion of applications from the creation of anatomical training models for complex surgical procedures to the printing of tissue engineering constructs. In addition to achieving the macroscale geometry of organs and tissues, a print layer thickness as small as 20 mm allows for reproduction of the microarchitectures of bone and other tissues. Techniques with even higher precision are currently being investigated to enable reproduction of smaller tissue features such as hepatic lobules. Current research in tissue engineering focuses on the development of compatible methods (printers) and materials (bioinks) that are capable of producing biomimetic scaffolds. In this review, an overview of current 3D printing techniques used in tissue engineering is provided with an emphasis on the printing mechanism and the resultant scaffold characteristics. Current practical challenges and technical limitations are emphasized and future trends of bioprinting are discussed.
AUTHOR Visscher, Dafydd O. and Farré-Guasch, Elisabet and Helder, Marco N. and Gibbs, Susan and Forouzanfar, Tymour and van Zuijlen, Paul P. and Wolff, Jan
Title Advances in Bioprinting Technologies for Craniofacial Reconstruction [Abstract]
Year 2016
Journal/Proceedings Trends in Biotechnology
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Abstract
Recent developments in craniofacial reconstruction have shown important advances in both the materials and methods used. While autogenous tissue is still considered to be the gold standard for these reconstructions, the harvesting procedure remains tedious and in many cases causes significant donor site morbidity. These limitations have subsequently led to the development of less invasive techniques such as 3D bioprinting that could offer possibilities to manufacture patient-tailored bioactive tissue constructs for craniofacial reconstruction. Here, we discuss the current technological and (pre)clinical advances of 3D bioprinting for use in craniofacial reconstruction and highlight the challenges that need to be addressed in the coming years. Recent developments in craniofacial reconstruction have shown important advances in both the materials and methods used. While autogenous tissue is still considered to be the gold standard for these reconstructions, the harvesting procedure remains tedious and in many cases causes significant donor site morbidity. These limitations have subsequently led to the development of less invasive techniques such as 3D bioprinting that could offer possibilities to manufacture patient-tailored bioactive tissue constructs for craniofacial reconstruction. Here, we discuss the current technological and (pre)clinical advances of 3D bioprinting for use in craniofacial reconstruction and highlight the challenges that need to be addressed in the coming years.
AUTHOR Ozbolat, Ibrahim T. and Peng, Weijie and Ozbolat, Veli
Title Application areas of 3D bioprinting [Abstract]
Year 2016
Journal/Proceedings Drug Discovery Today
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Abstract
Three dimensional (3D) bioprinting has been a powerful tool in patterning and precisely placing biologics, including living cells, nucleic acids, drug particles, proteins and growth factors, to recapitulate tissue anatomy, biology and physiology. Since the first time of cytoscribing cells demonstrated in 1986, bioprinting has made a substantial leap forward, particularly in the past 10 years, and it has been widely used in fabrication of living tissues for various application areas. The technology has been recently commercialized by several emerging businesses, and bioprinters and bioprinted tissues have gained significant interest in medicine and pharmaceutics. This Keynote review presents the bioprinting technology and covers a first-time comprehensive overview of its application areas from tissue engineering and regenerative medicine to pharmaceutics and cancer research.
AUTHOR H{"{o}}lzl, Katja and Lin, Shengmao and Tytgat, Liesbeth and Vlierberghe, Sandra Van and Gu, Linxia and Ovsianikov, Aleksandr
Title Bioink properties before, during and after 3D bioprinting [Abstract]
Year 2016
Journal/Proceedings Biofabrication
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Abstract
Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material–cell interaction.
AUTHOR Wu, Changsheng and Wang, Ben and Zhang, Chuck and Wysk, Richard A. and Chen, Yi-Wen
Title Bioprinting: an assessment based on manufacturing readiness levels [Abstract]
Year 2016
Journal/Proceedings Critical Reviews in Biotechnology
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Abstract
AbstractOver the last decade, bioprinting has emerged as a promising technology in the fields of tissue engineering and regenerative medicine. With recent advances in additive manufacturing, bioprinting is poised to provide patient-specific therapies and new approaches for tissue and organ studies, drug discoveries and even food manufacturing. Manufacturing Readiness Level (MRL) is a method that has been applied to assess manufacturing maturity and to identify risks and gaps in technology-manufacturing transitions. Technology Readiness Level (TRL) is used to evaluate the maturity of a technology. This paper reviews recent advances in bioprinting following the MRL scheme and addresses corresponding MRL levels of engineering challenges and gaps associated with the translation of bioprinting from lab-bench experiments to ultimate full-scale manufacturing of tissues and organs. According to our step-by-step TRL and MRL assessment, after years of rigorous investigation by the biotechnology community, bioprinting is on the cusp of entering the translational phase where laboratory research practices can be scaled up into manufacturing products specifically designed for individual patients.
AUTHOR Caetano, Guilherme and Violante, Ricardo and Sant{'{}}Ana, Ana Beatriz and Murashima, Adriana Batista and Domingos, Marco and Gibson, Andrew and B{'{a}}rtolo, Paulo and Frade, Marco Andrey
Title Cellularized versus decellularized scaffolds for bone regeneration [Abstract]
Year 2016
Journal/Proceedings Materials Letters
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Abstract
Abstract An optimal scaffold based strategy for in vivo repair of large bone defects and its associated problems is presented in this work. Three polymeric scaffolds produced by using an extrusion-based additive manufacturing system were examined in a rat critical bone defect model: scaffolds without cells, with undifferentiated Adipose-derived mesenchymal stem cells (ADSCs) and differentiated {ADSCs} (osteoblasts). Scaffolds with undifferentiated cells seem to be the best strategy as they exhibited around 22% more bone formation than natural bone healing, and around 15% more than the two other cases. Authors observed that scaffolds enabled cell migration and tissue formation. Results suggest that undifferentiated {ADSCs} strongly contribute to new bone formation with no rejection if scaffolds are used to support cell migration, proliferation and differentiation. Our long-term goal is to engineer high-quality cell seeded-scaffolds (autograft and allograft) for bone regeneration, mainly in elderly patients.
AUTHOR Ozbolat, Ibrahim T. and Hospodiuk, Monika
Title Current advances and future perspectives in extrusion-based bioprinting [Abstract]
Year 2016
Journal/Proceedings Biomaterials
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Abstract
Abstract Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in {EBB} technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine.
AUTHOR Ozbolat, Ibrahim T. and Moncal, Kazim K. and Gudapati, Hemanth
Title Evaluation of bioprinter technologies [Abstract]
Year 2016
Journal/Proceedings Additive Manufacturing
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Abstract
Abstract Since the first printing of biologics with cytoscribing as demonstrated by Klebe in 1986, three dimensional (3D) bioprinting has made a substantial leap forward, particularly in the last decade. It has been widely used in fabrication of living tissues for various application areas such as tissue engineering and regenerative medicine research, transplantation and clinics, pharmaceutics and high-throughput screening, and cancer research. As bioprinting has gained interest in the medical and pharmaceutical communities, the demand for bioprinters has risen substantially. A myriad of bioprinters have been developed at research institutions worldwide and several companies have emerged to commercialize advanced bioprinter technologies. This paper prefaces the evolution of the field of bioprinting and presents the first comprehensive review of existing bioprinter technologies. Here, a comparative evaluation is performed for bioprinters; limitations with the current bioprinter technologies are discussed thoroughly and future prospects of bioprinters are provided to the reader.
AUTHOR Passamai, V. E. and Dernowsek, J. A. and Nogueira, J. and Lara, V. and Vilalba, F. and Mironov, V. A. and Rezende, R. A. and da Silva, J. V.
Title From 3D Bioprinters to a fully integrated Organ Biofabrication Line [Abstract]
Year 2016
Journal/Proceedings Journal of Physics: Conference Series
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Abstract
About 30 years ago, the 3D printing technique appeared. From that time on, engineers in medical science field started to look at 3D printing as a partner. Firstly, biocompatible and biodegradable 3D structures for cell seeding called “scaffolds” were fabricated for in vitro and in vivo animal trials. The advances proved to be of great importance, but, the use of scaffolds faces some limitations, such as low homogeneity and low density of cell aggregates. In the last decade, 3D bioprinting technology emerged as a promising approach to overcome these limitations and as one potential solution to the challenge of organ fabrication, to obtain very similar 3D human tissues, not only for transplantation, but also for drug discovery, disease research and to decrease the usage of animals in laboratory experimentation. 3D bioprinting allowed the fabrication of 3D alive structures with higher and controllable cell density and homogeneity. Other advantage of biofabrication is that the tissue constructs are solid scaffold-free. This paper presents the 3D bioprinting technology; equipment development, stages and components of a complex Organ Bioprinting Line (OBL) and the importance of developing a Virtual OBL.
AUTHOR Gross, Bethany and Lockwood, Sarah Y. and Spence, Dana M.
Title Recent Advances in Analytical Chemistry by 3D Printing
Year 2016
Journal/Proceedings Analytical Chemistry
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AUTHOR Arslan-Yildiz, Ahu and Assal, Rami El and Chen, Pu and Guven, Sinan and Inci, Fatih and Demirci, Utkan
Title Towards artificial tissue models: past, present, and future of 3D bioprinting [Abstract]
Year 2016
Journal/Proceedings Biofabrication
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Abstract
Regenerative medicine and tissue engineering have seen unprecedented growth in the past decade, driving the field of artificial tissue models towards a revolution in future medicine. Major progress has been achieved through the development of innovative biomanufacturing strategies to pattern and assemble cells and extracellular matrix (ECM) in three-dimensions (3D) to create functional tissue constructs. Bioprinting has emerged as a promising 3D biomanufacturing technology, enabling precise control over spatial and temporal distribution of cells and ECM. Bioprinting technology can be used to engineer artificial tissues and organs by producing scaffolds with controlled spatial heterogeneity of physical properties, cellular composition, and ECM organization. This innovative approach is increasingly utilized in biomedicine, and has potential to create artificial functional constructs for drug screening and toxicology research, as well as tissue and organ transplantation. Herein, we review the recent advances in bioprinting technologies and discuss current markets, approaches, and biomedical applications. We also present current challenges and provide future directions for bioprinting research.
AUTHOR Rimann, Markus and Laternser, Sandra and Keller, Hansj{"{o}}rg and Leupin, Olivier and Graf-Hausner, Ursula
Title 3D Bioprinted Muscle and Tendon Tissues for Drug Development
Year 2015
Journal/Proceedings {CHIMIA} International Journal for Chemistry
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AUTHOR Hockaday, Laura
Title 3D Bioprinting: A Deliberate Business
Year 2015
Journal/Proceedings Genetic Engineering & Biotechnology News
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AUTHOR Ho, Chee Meng Benjamin and Ng, Sum Huan and Yoon, Yong-Jin
Title A review on 3D printed bioimplants [Abstract]
Year 2015
Journal/Proceedings International Journal of Precision Engineering and Manufacturing
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Abstract
Additive manufacturing (AM) also known as 3D printing have been making inroads into medical applications such as surgical models and tools, tooling equipment, medical devices. One key area researchers are looking into is bioimplants. With the improvement and development of AM technologies, many different bioimplants can be made using 3D printing. Different biomaterials and various AM technologies can be used to create customized bioimplants to suit the individual needs. With the aid of 3D printing this could lead to new foam and design of bioimplants in the near further. Therefore, the purpose of this review articles is to (1) Describe the various AM technologies and process used to make bioimplants, (2) Different types of bioimplants printed with AM and (3) Discuss some of the challenges and future developments for 3D printed bioimplants.
AUTHOR Rezende, R. A. and Selishchev, S. V. and Kasyanov, V. A. and da Silva, J. V. L. and Mironov, V. A.
Title An Organ Biofabrication Line: Enabling Technology for Organ Printing. Part II: from Encapsulators to Biofabrication Line [Abstract]
Year 2013
Journal/Proceedings Biomedical Engineering
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Abstract
The first part of this review was published in Biomedical Engineering, No. 3, 2013. This second part discusses development and application of tissue spheroid encapsulators, robotics bioprinters, bioreactors, and problems of computer design of biofabrication lines.
AUTHOR Quadri, Faisal and Soman, Soja Saghar and Vijayavenkataraman, Sanjairaj
Title Progress in cardiovascular bioprinting [Abstract]
Year 2
Journal/Proceedings Artificial Organs
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Abstract Cardiovascular disease has been the leading cause of death globally for the past 15 years. Following a major cardiac disease episode, the ideal treatment would be the replacement of the damaged tissue, due to the limited regenerative capacity of cardiac tissues. However, we suffer from a chronic organ donor shortage which causes approximately 20 people to die each day waiting to receive an organ. Bioprinting of tissues and organs can potentially alleviate this burden by fabricating low cost tissue and organ replacements for cardiac patients. Clinical adoption of bioprinting in cardiovascular medicine is currently limited by the lack of systematic demonstration of its effectiveness, high costs, and the complexity of the workflow. Here, we give a concise review of progress in cardiovascular bioprinting and its components. We further discuss the challenges and future prospects of cardiovascular bioprinting in clinical applications.