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You are researching: Skin Tissue Engineering
Tissue and Organ Biofabrication
Skin Tissue Engineering
Drug Delivery
Biological Molecules
Solid Dosage Drugs
Stem Cells
Personalised Pharmaceuticals
Inducend Pluripotent Stem Cells (IPSCs)
Drug Discovery
Cancer Cell Lines
Cell Type
All Groups
- Cell Type
- T cells
- Human Umbilical Vein Endothelial Cells (HUVECs)
- Organoids
- Stem Cells
- Spheroids
- Meniscus Cells
- Synoviocytes
- Keratinocytes
- Skeletal Muscle-Derived Cells (SkMDCs)
- Neurons
- Macrophages
- Human Trabecular Meshwork Cells
- Endothelial
- CardioMyocites
- Melanocytes
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- Neutrophils
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- Smooth Muscle Cells
- Institution
- Adolphe Merkle Institute Fribourg
- Halle-Wittenberg University
- Baylor College of Medicine
- INM – Leibniz Institute for New Materials
- National Yang Ming Chiao Tung University
- University of Vilnius
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- Harbin Institute of Technology
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- Anhui Polytechnic
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- University of Michigan, Biointerfaces Institute
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- University of Aveiro
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- Biomaterials & Bioinks
- Application
- Personalised Pharmaceuticals
- Bioelectronics
- Biomaterial Processing
- Tissue Models – Drug Discovery
- Industrial
- Drug Discovery
- In Vitro Models
- Robotics
- Electronics – Robotics – Industrial
- Medical Devices
- Tissue and Organ Biofabrication
- Cartilage Tissue Engineering
- Bone Tissue Engineering
- Dental Tissue Engineering
- Drug Delivery
- Urethra Tissue Engineering
- Skin Tissue Engineering
- Uterus Tissue Engineering
- Nerve – Neural Tissue Engineering
- Meniscus Tissue Engineering
- Heart – Cardiac Patches Tissue Engineering
- Adipose Tissue Engineering
- Trachea Tissue Engineering
- Ocular Tissue Engineering
- Intervertebral Disc (IVD) Tissue Engineering
- Muscle Tissue Engineering
- Liver tissue Engineering
- BioSensors
- Review Paper
- Printing Technology
- Biomaterial
- Solid Dosage Drugs
- Thermoplastics
- Coaxial Extruder
- Non-cellularized gels/pastes
- 2-hydroxyethyl-methacrylate (HEMA)
- Phenylacetylene
- Magnetorheological fluid (MR fluid – MRF)
- Salecan
- Poly(vinyl alcohol) (PVA)
- PEDOT
- Jeffamine
- Poly(methyl methacrylate) (PMMA)
- Polyethylene
- SEBS
- Polypropylene Oxide (PPO)
- Carbopol
- Sucrose Acetate
- Epoxy
- poly (ethylene-co -vinyl acetate) (PEVA)
- Poly(itaconate-co-citrate-cooctanediol) (PICO)
- Poly(N-isopropylacrylamide) (PNIPAAm)
- Mineral Oil
- poly(octanediol-co-maleic anhydride-co-citrate) (POMaC)
- Poly(Oxazoline)
- Poly(trimethylene carbonate)
- 2-hydroxyethyl) methacrylate (HEMA)
- Zein
- Acrylamide
- Pluronic – Poloxamer
- Polyisobutylene
- Paraffin
- Silicone
- Konjac Gum
- Polyphenylene Oxide
- Ionic Liquids
- Polyvinylpyrrolidone (PVP)
- Gelatin-Sucrose Matrix
- Salt-based
- Chlorella Microalgae
- Acrylates
- Poly(Vinyl Formal)
- Micro/nano-particles
- Biological Molecules
- Bioinks
- Hyaluronic Acid
- Peptide gel
- Methacrylated Silk Fibroin
- Pantoan Methacrylate
- Polyethylene glycol (PEG) based
- α-Bioink
- Poly(Acrylic Acid)
- Collagen
- Elastin
- Heparin
- sulfobetaine methacrylate (SBMA)
- Gelatin
- Matrigel
- Gellan Gum
- Methacrylated Chitosan
- Methacrylated hyaluronic acid (HAMA)
- Pectin
- Silk Fibroin
- Pyrogallol
- Xanthan Gum
- Fibrinogen
- Fibrin
- Paeoniflorin
- Fibronectin
- (2-Hydroxypropyl)methacrylamide (HPMA)
- Methacrylated Collagen (CollMA)
- Carrageenan
- Glucosamine
- Chitosan
- Glycerol
- Poly(glycidol)
- Alginate
- Agarose
- Gelatin-Methacryloyl (GelMA)
- methacrylated chondroitin sulfate (CSMA)
- Cellulose
- Novogel
- carboxybetaine acrylamide (CBAA)
- Ceramics
- Decellularized Extracellular Matrix (dECM)
- Metals
- Bioprinting Technologies
- Bioprinting Applications
AUTHOR
Title
Utilization of patterned bioprinting for heterogeneous and physiologically representative reconstructed epidermal skin models
[Abstract]
Year
2021
Journal/Proceedings
Scientific Reports
Reftype
Madiedo-Podvrsan2021
DOI/URL
DOI
Groups
AbstractOrganotypic skin tissue models have decades of use for basic research applications, the treatment of burns, and for efficacy/safety evaluation studies. The complex and heterogeneous nature of native human skin however creates difficulties for the construction of physiologically comparable organotypic models. Within the present study, we utilized bioprinting technology for the controlled deposition of separate keratinocyte subpopulations to create a reconstructed epidermis with two distinct halves in a single insert, each comprised of a different keratinocyte sub-population, in order to better model heterogonous skin and reduce inter-sample variability. As an initial proof-of-concept, we created a patterned epidermal skin model using GPF positive and negative keratinocyte subpopulations, both printed into 2 halves of a reconstructed skin insert, demonstrating the feasibility of this approach. We then demonstrated the physiological relevance of this bioprinting technique by generating a heterogeneous model comprised of dual keratinocyte population with either normal or low filaggrin expression. The resultant model exhibited a well-organized epidermal structure with each half possessing the phenotypic characteristics of its constituent cells, indicative of a successful and stable tissue reconstruction. This patterned skin model aims to mimic the edge of lesions as seen in atopic dermatitis or ichthyosis vulgaris, while the use of two populations within a single insert allows for paired statistics in evaluation studies, likely increasing study statistical power and reducing the number of models required per study. This is the first report of human patterned epidermal model using a predefined bioprinted designs, and demonstrates the relevance of bioprinting to faithfully reproduce human skin microanatomy.
AUTHOR
Title
A 3D biofabricated cutaneous squamous cell carcinoma tissue model with multi-channel confocal microscopy imaging biomarkers to quantify antitumor effects of chemotherapeutics in tissue
[Abstract]
Year
2020
Journal/Proceedings
Oncotarget; Vol 11, No 27
Reftype
DOI/URL
URL
Groups
Abstract// James R. Browning 1 , Paige Derr 2 , Kristy Derr 2 , Nicole Doudican 3 , Sam Michael 2 , Samantha R. Lish 1 , Nicholas A. Taylor 3 , James G. Krueger 1 , Marc Ferrer 2 , John A. Carucci 3 and Daniel S. Gareau 1 1 Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA 2 National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA 3 The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA Correspondence to: Daniel S. Gareau, email: dgareau@rockefeller.edu Keywords: squamous cell carcinoma; screening; 3D printing; in vitro model; confocal microscopy Received: January 05, 2020 Accepted: April 03, 2020 Published: July 07, 2020 ABSTRACT Cutaneous squamous cell carcinoma (cSCC) causes approximately 10,000 deaths annually in the U. S. Current therapies are largely ineffective against metastatic and locally advanced cSCC. There is a need to identify novel, effective, and less toxic small molecule cSCC therapeutics. We developed a 3-dimensional bioprinted skin (3DBPS) model of cSCC tumors together with a microscopy assay to test chemotherapeutic effects in tissue. The full thickness SCC tissue model was validated using hematoxylin and eosin (H&E) and immunohistochemical histological staining, confocal microscopy, and cDNA microarray analysis. A nondestructive, 3D fluorescence confocal imaging assay with tdTomato-labeled A431 SCC and ZsGreen-labeled keratinocytes was developed to test efficacy and general toxicity of chemotherapeutics. Fluorescence-derived imaging biomarkers indicated that 50% of cancer cells were killed in the tissue after 1?M 5-Fluorouracil 48-hour treatment, compared to a baseline of 12% for untreated controls. The imaging biomarkers also showed that normal keratinocytes were less affected by treatment (11% killed) than the untreated tissue, which had no significant killing effect. Data showed that 5-Fluorouracil selectively killed cSCC cells more than keratinocytes. Our 3DBPS assay platform provides cellular-level measurement of cell viability and can be adapted to achieve nondestructive high-throughput screening (HTS) in bio-fabricated tissues.
AUTHOR
Title
Fully 3D Bioprinted Skin Equivalent Constructs with Validated Morphology and Barrier Function
[Abstract]
Year
2019
Journal/Proceedings
Tissue Engineering Part C: Methods
Reftype
DOI/URL
DOI
Groups
AbstractDevelopment of high throughput, reproducible, three-dimensional bioprinted skin equivalents that are morphologically and functionally comparable to native skin tissue is advancing research in skin diseases, and providing a physiologically relevant platform for the development of therapeutics, transplants for regenerative medicine, and testing of skin products like cosmetics. Current protocols for the production of engineered skin rafts are limited in their ability to control three dimensional geometry of the structure and contraction leading to variability of skin function between constructs. Here we describe a method for the biofabrication of skin equivalents that are fully bioprinted using an open market bioprinter, made with commercially available primary cells and natural hydrogels. The unique hydrogel formulation allows for the production of a human-like skin equivalent with minimal lateral tissue contraction in a multiwell plate format, thus making them suitable for high throughput bioprinting in a single print with fast print and relatively short incubation times. The morphology and barrier function of the fully three-dimensional bioprinted skin equivalents are validated by immunohistochemistry staining, optical coherence tomography, and permeation assays.
AUTHOR
Title
A biofabricated vascularized skin model of atopic dermatitis for preclinical studies
[Abstract]
Year
2020
Journal/Proceedings
Biofabrication
Reftype
DOI/URL
DOI
Groups
AbstractThree-dimensional (3D) biofabrication techniques enable the production of multicellular tissue models as assay platforms for drug screening. The increased cellular and physiological complexity in these 3D tissue models should recapitulate the relevant biological environment found in the body. Here we describe the use of 3D bioprinting techniques to fabricate skin equivalent tissues of varying physiological complexity, including human epidermis, non-vascularized and vascularized full-thickness skin tissue equivalents, in a multi-well platform to enable drug screening. Human keratinocytes, fibroblasts, and pericytes, and induced pluripotent stem cell (iPSC)-derived endothelial cells were used in the biofabrication process to produce the varying complexity. The skin equivalents exhibit the correct structural markers of dermis and epidermis stratification, with physiological functions of the skin barrier. The robustness, versatility and reproducibility of the biofabrication techniques are further highlighted by the generation of atopic dermatitis (AD)-disease like tissues. These AD models demonstrate several clinical hallmarks of the disease, including: (i) spongiosis and hyperplasia; (ii) early and terminal expression of differentiation proteins; and (iii) increases in levels of pro-inflammatory cytokines. We show the pre-clinical relevance of the biofabricated AD tissue models to correct disease phenotype by testing the effects of dexamethasone, an anti-inflammatory corticosteroid, and three Janus Kinase inhibitors from clinical trials for AD. This study demonstrates the development of a versatile and reproducible bioprinting approach to create human skin equivalents with a range of cellular complexity for disease modelling. In addition, we establish several assay readouts that are quantifiable, robust, AD relevant, and can be scaled up for compound screening. The results show that the cellular complexity of the tissues develops a more physiologically relevant AD disease model. Thus, the skin models in this study offer an in vitro approach for the rapid understanding of pathological mechanisms, and testing for efficacy of action and toxic effects of drugs.
AUTHOR
Year
2018
Journal/Proceedings
Biofabrication
Reftype
DOI/URL
DOI
Groups
AbstractThree-dimensional (3D) pigmented human skin constructs have been fabricated using a 3D bioprinting approach. The 3D pigmented human skin constructs are obtained from using three different types of skin cells (keratinocytes, melanocytes and fibroblasts from three different skin donors) and they exhibit similar constitutive pigmentation (pale pigmentation) as the skin donors. A two-step drop-on-demand bioprinting strategy facilitates the deposition of cell droplets to emulate the epidermal melanin units (pre-defined patterning of keratinocytes and melanocytes at the desired positions) and manipulation of the microenvironment to fabricate 3D biomimetic hierarchical porous structures found in native skin tissue. The 3D bioprinted pigmented skin constructs are compared to the pigmented skin constructs fabricated by conventional a manual-casting approach; in-depth characterization of both the 3D pigmented skin constructs has indicated that the 3D bioprinted skin constructs have a higher degree of resemblance to native skin tissue in term of the presence of well-developed stratified epidermal layers and the presence of a continuous layer of basement membrane proteins as compared to the manually-cast samples. The 3D bioprinting approach facilitates the development of 3D in vitro pigmented human skin constructs for potential toxicology testing and fundamental cell biology research.
AUTHOR
Title
Combining bioengineered human skin with bioprinted cartilage for ear reconstruction
[Abstract]
Year
2023
Journal/Proceedings
Science Advances
Reftype
DOI/URL
DOI
Groups
AbstractMicrotia is a congenital disorder that manifests as a malformation of the external ear leading to psychosocial problems in affected children. Here, we present a tissue-engineered treatment approach based on a bioprinted autologous auricular cartilage construct (EarCartilage) combined with a bioengineered human pigmented and prevascularized dermo-epidermal skin substitute (EarSkin) tested in immunocompromised rats. We confirmed that human-engineered blood capillaries of EarSkin connected to the recipient’s vasculature within 1 week, enabling rapid blood perfusion and epidermal maturation. Bioengineered EarSkin displayed a stratified epidermis containing mature keratinocytes and melanocytes. The latter resided within the basal layer of the epidermis and efficiently restored the skin color. Further, in vivo tests demonstrated favorable mechanical stability of EarCartilage along with enhanced extracellular matrix deposition. In conclusion, EarCartilage combined with EarSkin represents a novel approach for the treatment of microtia with the potential to circumvent existing limitations and improve the aesthetic outcome of microtia reconstruction. A therapy for microtia patients utilizes bioprinted auricular cartilage combined with a tissue-engineered skin graft.
AUTHOR
Title
3D bioprinting of Salvianolic acid B-sodium alginate-gelatin skin scaffolds promotes diabetic wound repair via antioxidant, anti-inflammatory, and proangiogenic effects
[Abstract]
Year
2024
Journal/Proceedings
Biomedicine & Pharmacotherapy
Reftype
Groups
AbstractIn patients with diabetic wounds, wound healing is impaired due to the presence of persistent oxidative stress, an altered inflammatory response, and impaired angiogenesis and epithelization. Salvianolic acid B (SAB), which is derived from the Chinese medicinal plant Salvia miltiorrhiza, has been found to exhibit antioxidant, anti-inflammatory, and proangiogenic effects. Previous studies have used 3D bioprinting technology incorporating sodium alginate (SA) and gelatin (Gel) as basic biomaterials to successfully produce artificial skin. In the current study, 3D bioprinting technology was used to incorporate SAB into SA-Gel to form a novel SAB-SA-Gel composite porous scaffold. The morphological characteristics, physicochemical characteristics, biocompatibility, and SAB release profile of the SAB-SA-Gel scaffolds were evaluated in vitro. In addition, the antioxidant, anti-inflammatory, and proangiogenic abilities of the SAB-SA-Gel scaffolds were evaluated in cells and in a rat model. Analysis demonstrated that 1.0 wt% (the percentage of SAB in the total weight of the solution containing SA and Gel) SAB-SA-Gel scaffolds had strong antioxidant, anti-inflammatory, and proangiogenic properties both in cells and in the rat model. The 1.0% SAB-SA-Gel scaffold reduced the expression of tumor necrosis factor-α, interleukin-6, and interluekin-1β and increased the expression of transforming growth factor-β. In addition, this scaffold removed excessive reactive oxygen species by increasing the expression of superoxide dismutase, thereby protecting fibroblasts from injury. The scaffold increased the expression of vascular endothelial growth factor and platelet/endothelial cell adhesion molecule-1, accelerated granulation tissue regeneration and collagen deposition, and promoted wound healing. These findings suggest that this innovative scaffold may have promise as a simple and efficient approach to managing diabetic wound repair.
AUTHOR
Title
3D-Printed and Recombinant Spider Silk Particle Reinforced Collagen Composite Scaffolds for Soft Tissue Engineering
[Abstract]
Year
2024
Journal/Proceedings
Advanced Functional Materials
Reftype
DOI/URL
DOI
Groups
AbstractAbstract Collagen is one main component of the extracellular matrix (ECM) in natural tissues and is, therefore, well suited as a biomaterial for tissue engineering. In this study, a method is presented to 3D-bioprint collagen into a precipitation bath comprising recombinantly produced spider silk protein eADF4(C16) yielding a composite with excellent mechanical properties. The spider silk precipitation bath induced assembly of the collagen into fibrils, and subsequent addition of potassium phosphate buffer lead to the formation of silk particles and stabilization of the collagen fibrils. The produced collagen-silk composite scaffolds show an internal structure of homogeneously distributed and interacting collagen fibrils and spider silk particles with significantly better mechanical properties compared to plain collagen scaffolds. Further, enzymatic degradation assays of the scaffolds over a 7-day period show higher stability of the collagen-silk scaffolds compared to plain collagen scaffolds in the presence of wound proteases. Using the spider silk variant eADF4(C16-RGD) further increases compressive stress and elastic modulus compared to that of the unmodified variant. Finally, it is shown that the unique collagen-spider silk composite scaffolds comprising the cell-binding domains of collagen and the RGD sequence in the spider silk variant represent a promising material for soft tissue regeneration.
AUTHOR
Title
Recent advances in the 3D skin bioprinting for regenerative medicine: Cells, biomaterials, and methods
[Abstract]
Year
2024
Journal/Proceedings
Journal of Biomaterials Applications
Reftype
DOI/URL
DOI
Groups
AbstractThe skin is a tissue constantly exposed to the risk of damage, such as cuts, burns, and genetic disorders. The standard treatment is autograft, but it can cause pain to the patient being extremely complex in patients suffering from burns on large body surfaces. Considering that there is a need to develop technologies for the repair of skin tissue like 3D bioprinting. Skin is a tissue that is approximately 1/16 of the total body weight and has three main layers: epidermis, dermis, and hypodermis. Therefore, there are several studies using cells, biomaterials, and bioprinting for skin regeneration. Here, we provide an overview of the structure and function of the epidermis, dermis, and hypodermis, and showed in the recent research in skin regeneration, the main cells used, biomaterials studied that provide initial support for these cells, allowing the growth and formation of the neotissue and general characteristics, advantages and disadvantages of each methodology and the landmarks in recent research in the 3D skin bioprinting.
AUTHOR
Title
Technological advances in three-dimensional skin tissue engineering
Year
2023
Journal/Proceedings
REVIEWS ON ADVANCED MATERIALS SCIENCE
Reftype
DOI/URL
DOI
AUTHOR
Title
Bioprinting and plastic compression of large pigmented and vascularized human dermo-epidermal skin substitutes by means of a new robotic platform
[Abstract]
Year
2022
Journal/Proceedings
Journal of Tissue Engineering
Reftype
Groups
AbstractExtensive availability of engineered autologous dermo-epidermal skin substitutes (DESS) with functional and structural properties of normal human skin represents a goal for the treatment of large skin defects such as severe burns. Recently, a clinical phase I trial with this type of DESS was successfully completed, which included patients own keratinocytes and fibroblasts. Yet, two important features of natural skin were missing: pigmentation and vascularization. The first has important physiological and psychological implications for the patient, the second impacts survival and quality of the graft. Additionally, accurate reproduction of large amounts of patient’s skin in an automated way is essential for upscaling DESS production. Therefore, in the present study, we implemented a new robotic unit (called SkinFactory) for 3D bioprinting of pigmented and pre-vascularized DESS using normal human skin derived fibroblasts, blood- and lymphatic endothelial cells, keratinocytes, and melanocytes. We show the feasibility of our approach by demonstrating the viability of all the cells after printing in vitro, the integrity of the reconstituted capillary network in vivo after transplantation to immunodeficient rats and the anastomosis to the vascular plexus of the host. Our work has to be considered as a proof of concept in view of the implementation of an extended platform, which fully automatize the process of skin substitution: this would be a considerable improvement of the treatment of burn victims and patients with severe skin lesions based on patients own skin derived cells.
AUTHOR
Title
Exploring the Potential of Alginate-Gelatin-Diethylaminoethyl Cellulose-Fibrinogen based Bioink for 3D Bioprinting of Skin Tissue Constructs
[Abstract]
Year
2022
Journal/Proceedings
Carbohydrate Polymer Technologies and Applications
Reftype
Groups
AbstractDesigning printable bioinks for 3D bioprinting capable of supporting cellular viability with post-printing functionality remains challenging. Native ECM offers several physical, chemical, and biological cues that are difficult to restore using only a single component. Herein, we have optimized a multicomponent-based bioink formulation comprising alginate (ALG), gelatin (GEL), diethylaminoethyl cellulose (DCEL) and fibrinogen (FIB), termed as ALG-GEL-DCEL-FIB bioink for potential application in bioprinting and biofabrication of skin tissue equivalents. The designed formulation was extensively studied for its printability, physico-chemical, rheological, and biocompatibility properties. Excellent printability, shape fidelity and cell-laden tissue equivalent printing were established using the RegenHu 3D Discovery Bioprinter. The human primary fibroblast and keratinocyte-laden bioprinted constructs exhibited good cell viability. Long term culture of 4 weeks comprising 5 days of air-liquid-interphase followed by 21 days of submerged culture produced biomimetic tissue histology in the ALG-GEL-DCEL-FIB bioink printed constructs. Specific epidermal-dermal marker expressions proving functionality were evident in immunohistochemical, biochemical and gene expression analysis. The ALG-GEL-DCEL-FIB bioink may be explored further for potential biofabrication and therapeutic applications.
AUTHOR
Title
Impact of microstructure on cell behavior and tissue mechanics in collagen and dermal decellularized extra-cellular matrices
[Abstract]
Year
2022
Journal/Proceedings
Acta Biomaterialia
Reftype
Groups
AbstractSkin models are used for many applications such as research and development or grafting. Unfortunately, most lack a proper microenvironment producing poor mechanical properties and inaccurate extra-cellular matrix composition and organization. In this report we focused on mechanical properties, extra-cellular matrix organization and cell interactions in human skin samples reconstructed with pure collagen or dermal decellularized extra-cellular matrices (S-dECM) and compared them to native human skin. We found that Full-thickness S-dECM samples presented stiffness two times higher than collagen gel and similar to ex vivo human skin, and proved for the first time that keratinocytes also impact dermal mechanical properties. This was correlated with larger fibers in S-dECM matrices compared to collagen samples and with a differential expression of F-actin, vinculin and tenascin C between S-dECM and collagen samples. This is clear proof of the microenvironment's impact on cell behaviors and mechanical properties. Statement of significance In vitro skin models have been used for a long time for clinical applications or in vitro knowledge and evaluation studies. However, most lack a proper microenvironment producing a poor combination of mechanical properties and appropriate biological outcomes, partly due to inaccurate extra-cellular matrix (ECM) composition and organization. This can lead to limited predictivity and weakness of skin substitutes after grafting. This study shows, for the first time, the importance of a complex and rich microenvironment on cell behaviors, matrix macro- and micro-organization and mechanical properties. The increased composition and organization complexity of dermal skin decellularized extra-cellular matrix populated with differentiated cells produces in vitro skin models closer to native human skin physiology.
AUTHOR
Title
Multi-Scale Analysis of the Composition, Structure, and Function of Decellularized Extracellular Matrix for Human Skin and Wound Healing Models
[Abstract]
Year
2022
Journal/Proceedings
Biomolecules
Reftype
Groups
AbstractThe extracellular matrix (ECM) is a complex mixture of structural proteins, proteoglycans, and signaling molecules that are essential for tissue integrity and homeostasis. While a number of recent studies have explored the use of decellularized ECM (dECM) as a biomaterial for tissue engineering, the complete composition, structure, and mechanics of these materials remain incompletely understood. In this study, we performed an in-depth characterization of skin-derived dECM biomaterials for human skin equivalent (HSE) models. The dECM materials were purified from porcine skin, and through mass spectrometry profiling, we quantified the presence of major ECM molecules, including types I, III, and VI collagen, fibrillin, and lumican. Rheological analysis demonstrated the sol-gel and shear-thinning properties of dECM materials, indicating their physical suitability as a tissue scaffold, while electron microscopy revealed a complex, hierarchical structure of nanofibers in dECM hydrogels. The dECM materials were compatible with advanced biofabrication techniques, including 3D printing within a gelatin microparticle support bath, printing with a sacrificial material, or blending with other ECM molecules to achieve more complex compositions and structures. As a proof of concept, we also demonstrate how dECM materials can be fabricated into a 3D skin wound healing model using 3D printing. Skin-derived dECM therefore represents a complex and versatile biomaterial with advantageous properties for the fabrication of next-generation HSEs.
AUTHOR
Year
2022
Journal/Proceedings
Bioengineered
Reftype
DOI/URL
DOI
Groups
AbstractABSTRACTArtificial skins have been used as skin substitutes for wound healing in the clinic, and as in vitro models for safety assessment in cosmetic and pharmaceutical industries. The three-dimensional (3D) bioprinting technique provides a promising strategy in the fabrication of artificial skins. Despite the technological advances, many challenges remain to be conquered, such as the complicated preparation conditions for bio-printed skin and the unavailability of stability and robustness of skin bioprinting. Here, we formulated a novel bio-ink composed of gelatin, sodium alginate and fibrinogen. By optimizing the ratio of components in the bio-ink, the design of the 3D model and the printing conditions, a fibroblasts-containing dermal layer construct was firstly fabricated, on the top of which laminin and keratinocytes were sequentially placed. Through air-liquid interface (ALI) culture by virtue of sterile wire mesh, a full-thickness skin tissue was thus prepared. HE and immunofluorescence staining showed that the bio-printed skin was not only morphologically representative of the human skin, but also expressed the specific markers related to epidermal differentiation and stratum corneum formation. The presented easy and robust preparation of full-thickness skin constructs provides a powerful tool for the establishment of artificial skins, holding critical academic significance and application value.
AUTHOR
Title
The efficacy of a paeoniflorin-sodium alginate-gelatin skin scaffold for the treatment of diabetic wound: An in vivo study in a rat model
[Abstract]
Year
2022
Journal/Proceedings
Biomedicine & Pharmacotherapy
Reftype
Groups
AbstractObjective To investigate the efficacy of a paeoniflorin-sodium alginate (SA)-gelatin skin scaffold for treating diabetic wound in a rat model. Methods Bioinks were prepared using various percentages of paeoniflorin in the total weight of a solution containing SA and gelatin. Skin scaffolds containing 0%, 1%, 3%, 5%, and 10% paeoniflorin were printed using 3D bioprinting technology, and scaffold microstructure was observed with scanning electron microscopy. Skin scaffolds were then used in rats with diabetic wounds. H&E staining, Masson staining, and immunohistochemical staining for IL-1β and CD31 were performed on days 7 and 14. Results All skin scaffolds had a mesh-like structure with uniform pore distribution. Wounds healed well in each group, with the 1% and 3% groups demonstrating the most complete healing. H&E staining showed that skin accessory organs had appeared in each group. On day 7, collagen deposition in the 3% group was higher than in the other groups (P<0.05), and IL-1β infiltration was lower in the 10% group than in the 3% group (P = 0.002). On day 14, IL-1β infiltration was not significantly different between the 10% and 3% groups (P = 0.078). The CD31 level was higher in the 3% group than in the other groups on days 7 and 14 (P<0.05). Conclusion A 3% paeoniflorin-SA-gelatin skin scaffold promoted the healing of diabetic wounds in rats. This scaffold promoted collagen deposition and microvascular regeneration and demonstrated anti-inflammatory properties, suggesting that this scaffold type could be used to treat diabetic wounds.
AUTHOR
Title
Layer-by-Layer 3D Constructs of Fibroblasts in Hydrogel for Examining Transdermal Penetration Capability of Nanoparticles
[Abstract]
Year
2016
Journal/Proceedings
Journal of Laboratory Automation
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Groups
AbstractNanoparticles are emerging transdermal delivery systems. Their size and surface properties determine their efficacy and efficiency to penetrate through the skin layers. This work utilizes three-dimensional (3D) bioprinting technology to generate a simplified artificial skin model to rapidly screen nanoparticles for their transdermal penetration ability. Specifically, this model is built through layer-by-layer alternate printing of blank collagen hydrogel and fibroblasts. Through controlling valve on-time, the spacing between printing lines could be accurately tuned, which could enable modulation of cell infiltration in the future. To confirm the effectiveness of this platform, a 3D construct with one layer of fibroblasts sandwiched between two layers of collagen hydrogel is used to screen silica nanoparticles with different surface charges for their penetration ability, with positively charged nanoparticles demonstrating deeper penetration, consistent with the observation from an existing study involving living skin tissue.
AUTHOR
Title
Polyelectrolyte gelatin-chitosan hydrogel optimized for 3D bioprinting in skin tissue engineering
[Abstract]
Year
2016
Journal/Proceedings
International Journal of Bioprinting
Reftype
Groups
AbstractBioprinting is a promising automated platform that enables the simultaneous deposition of multiple types of cells and biomaterials to fabricate complex three-dimensional (3D) tissue constructs. Most of the previous bioprinting works focused on collagen-based biomaterial, which has poor printability and long crosslinking time. This posed a immerse challenge to create a 3D construct with pre-determined shape and configuration. There is a need for a functional material with good printability in order to fabricate a 3D skin construct. Recently, the use of chitosan for wound healing applications has attracted huge attention due to its attractive traits such as its antimicrobial properties and ability to trigger hemostasis. In this paper, we report the modification of chitosan-based biomaterials for functional 3D bioprinting. Modification to the chitosan was carried out via the oppositely charged functional groups from chitosan and gelatin at a specific pH of ~pH 6.5 to form polyelectrolyte complexes. The polyelectrolyte hydrogels were evaluated in terms of chemical interactions within polymer blend, rheological properties (viscosities, storage and loss modulus), printing resolution at varying pressures and feed rates and biocompatibility. The chitosan-based hydrogels formulated in this work exhibited good printability at room temperature, high shape fidelity of the printed 3D constructs and good biocompatibility with fibroblast skin cells.
AUTHOR
Year
2015
Journal/Proceedings
Journal of laboratory automation
Reftype
DOI/URL
DOI
Groups
AbstractCells grown in 3D are more physiologically relevant than cells cultured in 2D. To use 3D models in substance testing and regenerative medicine, reproducibility and standardization are important. Bioprinting offers not only automated standardizable processes but also the production of complex tissue-like structures in an additive manner. We developed an all-in-one bioprinting solution to produce soft tissue models. The holistic approach included (1) a bioprinter in a sterile environment, (2) a light-induced bioink polymerization unit, (3) a user-friendly software, (4) the capability to print in standard labware for high-throughput screening, (5) cell-compatible inkjet-based printheads, (6) a cell-compatible ready-to-use BioInk, and (7) standard operating procedures. In a proof-of-concept study, skin as a reference soft tissue model was printed. To produce dermal equivalents, primary human dermal fibroblasts were printed in alternating layers with BioInk and cultured for up to 7 weeks. During long-term cultures, the models were remodeled and fully populated with viable and spreaded fibroblasts. Primary human dermal keratinocytes were seeded on top of dermal equivalents, and epidermis-like structures were formed as verified with hematoxylin and eosin staining and immunostaining. However, a fully stratified epidermis was not achieved. Nevertheless, this is one of the first reports of an integrative bioprinting strategy for industrial routine application.