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You are researching: CIC biomaGUNE
Solid Dosage Drugs
Stem Cells
Personalised Pharmaceuticals
Inducend Pluripotent Stem Cells (IPSCs)
Drug Discovery
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Tissue and Organ Biofabrication
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Biological Molecules
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- Review Paper
- Printing Technology
- Biomaterial
- Decellularized Extracellular Matrix (dECM)
- Metals
- Solid Dosage Drugs
- Thermoplastics
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- Non-cellularized gels/pastes
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- Poly(Vinyl Formal)
- 2-hydroxyethyl-methacrylate (HEMA)
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- poly (ethylene-co -vinyl acetate) (PEVA)
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- Poly(N-isopropylacrylamide) (PNIPAAm)
- Mineral Oil
- poly(octanediol-co-maleic anhydride-co-citrate) (POMaC)
- Poly(Oxazoline)
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- α-Bioink
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- Collagen
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- (2-Hydroxypropyl)methacrylamide (HPMA)
- Methacrylated Collagen (CollMA)
- Carrageenan
- Glucosamine
- Chitosan
- Glycerol
- Poly(glycidol)
- Alginate
- Agarose
- Gelatin-Methacryloyl (GelMA)
- methacrylated chondroitin sulfate (CSMA)
- Ceramics
- Bioprinting Technologies
- Bioprinting Applications
AUTHOR
Year
2024
Journal/Proceedings
Advanced Healthcare Materials
Reftype
DOI/URL
DOI
Groups
AbstractAbstract There is an unmet need for in vitro cancer models that emulate the complexity of human tissues. 3D-printed solid tumor micromodels based on decellularized extracellular matrices (dECMs) recreate the biomolecule-rich matrix of native tissue. Herein a 3D in vitro metastatic melanoma model that is amenable for drug screening purposes and recapitulates features of both the tumor and the skin microenvironment is described. Epidermal, basement membrane, and dermal biocompatible inks are prepared by means of combined chemical, mechanical, and enzymatic processes. Bioink printability is confirmed by rheological assessment and bioprinting, and bioinks are subsequently combined with melanoma cells and dermal fibroblasts to build complex 3D melanoma models. Cells are tracked by confocal microscopy and surface-enhanced Raman spectroscopy (SERS) mapping. Printed dECMs and cell tracking allow modeling of the initial steps of metastatic disease, and may be used to better understand melanoma cell behavior and response to drugs.
AUTHOR
Title
3D Bioprinted Tumor-Stroma Models of Triple-Negative Breast Cancer Stem Cells for Preclinical Targeted Therapy Evaluation
[Abstract]
Year
2024
Journal/Proceedings
ACS Appl. Mater. Interfaces
Reftype
DOI/URL
DOI
Groups
AbstractBreast cancer stem cells (CSCs) play a pivotal role in therapy resistance and tumor relapse, emphasizing the need for reliable in vitro models that recapitulate the complexity of the CSC tumor microenvironment to accelerate drug discovery. We present a bioprinted breast CSC tumor-stroma model incorporating triple-negative breast CSCs (TNB-CSCs) and stromal cells (human breast fibroblasts), within a breast-derived decellularized extracellular matrix bioink. Comparison of molecular signatures in this model with different clinical subtypes of bioprinted tumor-stroma models unveils a unique molecular profile for artificial CSC tumor models. We additionally demonstrate that the model can recapitulate the invasive potential of TNB-CSC. Surface-enhanced Raman scattering imaging allowed us to monitor the invasive potential of tumor cells in deep z-axis planes, thereby overcoming the depth-imaging limitations of confocal fluorescence microscopy. As a proof-of-concept application, we conducted high-throughput drug testing analysis to assess the efficacy of CSC-targeted therapy in combination with conventional chemotherapeutic compounds. The results highlight the usefulness of tumor-stroma models as a promising drug-screening platform, providing insights into therapeutic efficacy against CSC populations resistant to conventional therapies.
AUTHOR
Title
A Scaffold-Assisted 3D Cancer Cell Model for Surface-Enhanced Raman Scattering-Based Real-Time Sensing and Imaging
[Abstract]
Year
2024
Journal/Proceedings
ACS Nano
Reftype
DOI/URL
DOI
Groups
AbstractDespite recent advances in the development of scaffold-based three-dimensional (3D) cell models, challenges persist in imaging and monitoring cell behavior within these complex structures due to their heterogeneous cell distribution and geometries. Incorporating sensors into 3D scaffolds provides a potential solution for real-time, in situ sensing and imaging of biological processes such as cell growth and disease development. We introduce a 3D printed hydrogel-based scaffold capable of supporting both surface-enhanced Raman scattering (SERS) biosensing and imaging of 3D breast cancer cell models. The scaffold incorporates plasmonic nanoparticles and SERS tags, for sensing and imaging, respectively. We demonstrate the scaffold’s adaptability and modularity in supporting breast cancer spheroids, thereby enabling spatial and temporal monitoring of tumor evolution.
AUTHOR
Title
Engineering Proteins for PEDOT Dispersions: A New Horizon for Highly Mixed Ionic-Electronic Biocompatible Conducting Materials
[Abstract]
Year
2024
Journal/Proceedings
Small
Reftype
DOI/URL
DOI
Groups
AbstractAbstract Poly (3,4-ethylenedioxythiophene) (PEDOT) doped with polystyrene sulfonate (PSS) is the most used conducting polymer from energy to biomedical applications. Despite its exceptional properties, there is a need for developing new materials that can improve some of its inherent limitations, e.g., biocompatibility. In this context, doping PEDOT is propose with a robust recombinant protein with tunable properties, the consensus tetratricopeptide repeated protein (CTPR). The doping consists of an oxidative polymerization, where the PEDOT chains are stabilized by the negative charges of the CTPR protein. CTPR proteins are evaluated with three different lengths (3, 10, and 20 identical CTPR units) and optimized varied synthetic conditions. These findings revealed higher doping rate and oxidized state of the PEDOT chains when doped with the smallest scaffold (CTPR3). These PEDOT:CTPR hybrids possess ionic and electronic conductivity. Notably, PEDOT:CTPR3 displayed an electronic conductivity of 0.016 S cm−1, higher than any other reported protein-doped PEDOT. This result places PEDOT:CTPR3 at the level of PEDOT-biopolymer hybrids, and brings it closer in performance to PEDOT:PSS gold standard. Furthermore, PEDOT:CTPR3 dispersion is successfully optimized for inkjet printing, preserving its electroactivity properties after printing. This approach opens the door to the use of these novel hybrids for bioelectronics.
AUTHOR
Year
2024
Journal/Proceedings
Chem. Mater.
Reftype
DOI/URL
DOI
Groups
AbstractNanocomposites comprising hydrogels and plasmonic nanoparticles are attractive materials for tissue engineering, bioimaging, and biosensing. These materials are usually fabricated by adding colloidal nanoparticles to the uncured polymer mixture and thus require time-consuming presynthesis, purification, and ligand-exchange steps. Herein, we introduce approaches for rapid synthesis of gold nanostars (AuNSt) in situ on hydrogel substrates, including those with complex three-dimensional (3D) features. These methods enable selective AuNSt growth at the surface of the substrate, and the growth conditions can be tuned to tailor the nanoparticle size and density (coverage). We additionally demonstrate proof-of-concept applications of these nanocomposites for SERS sensing and imaging. High surface coverage with AuNSt enabled 1-2 orders of magnitude higher SERS signals compared to plasmonic hydrogels loaded with premade colloids. Importantly, AuNSt can be prepared without the addition of any potentially cytotoxic surfactants, thereby ensuring a high biocompatibility. Overall, in situ growth becomes a versatile and straightforward approach for the fabrication of plasmonic biomaterials.
AUTHOR
Title
Multiplex Determination of Glycan Profiles on Urinary Prostate-Specific Antigen by Quartz-Crystal Microbalance Combined with Surface-Enhanced Raman Scattering
[Abstract]
Year
2024
Journal/Proceedings
ACS Sens.
Reftype
DOI/URL
DOI
Groups
AbstractProstate cancer remains a major health concern, with prostate-specific antigen (PSA) being a key biomarker for its detection and monitoring. However, PSA levels often fall into a “gray zone”, where PSA levels are not clearly indicative of cancer, thus complicating early diagnosis and treatment decisions. Glycosylation profiles, which often differ between healthy and diseased cells, have emerged as potential biomarkers to enhance the specificity and sensitivity of cancer diagnosis in these ambiguous cases. We propose the integration of two complementary techniques, namely quartz-crystal microbalance with dissipation (QCM-D) and surface-enhanced Raman scattering (SERS) to study PSA glycan profiles. QCM-D offers real-time operation, PSA mass quantification, and label-free detection with high sensitivity, as well as enhanced specificity and reduced cross-reactivity when using nucleic acid aptamers as capture ligands. Complementary SERS sensing enables the determination of the glycosylation pattern on PSA, at low concentrations and without the drawbacks of photobleaching, thereby facilitating multiplexed glycosylation pattern analysis. This integrated setup could retrieve a data set comprising analyte concentrations and associated glycan profiles in relevant biological samples, which may eventually improve early disease detection and monitoring. Prostate-specific antigen (PSA), a glycoprotein secreted by prostate epithelial cells, serves as our proof-of-concept analyte. Our platform allows multiplex targeting of PSA multiplex glycosylation profiles of PSA at “gray zone” concentrations for prostate cancer diagnosis. We additionally show the use of SERS for glycan analysis in PSA secreted from prostate cancer cell lines after androgen-based treatment. Differences in PSA glycan profiles from resistant cell lines after androgen-based treatment may eventually improve cancer treatment.
AUTHOR
Year
2023
Journal/Proceedings
Materials Today Bio
Reftype
Groups
AbstractThe use of three-dimensional (3D) bioprinting has been proposed for the reproducible production of 3D disease models that can be used for high-throughput drug testing and personalized medicine. However, most such models insufficiently reproduce the features and environment of real tumors. We report the development of bioprinted in vitro 3D tumor models for breast cancer, which physically and biochemically mimic important aspects of the native tumor microenvironment, designed to study therapeutic efficacy. By combining a mix of breast decellularized extracellular matrix and methacrylated hyaluronic acid with tumor-derived cells and non-cancerous stromal cells of biological relevance to breast cancer, we show that biological signaling pathways involved in tumor progression can be replicated in a carefully designed tumor-stroma environment. Finally, we demonstrate proof-of-concept application of these models as a reproducible platform for investigating therapeutic responses to commonly used chemotherapeutic agents.
AUTHOR
Title
An Electroactive and Self-Assembling Bio-Ink, based on Protein-Stabilized Nanoclusters and Graphene, for the Manufacture of Fully Inkjet-Printed Paper-Based Analytical Devices
[Abstract]
Year
2023
Journal/Proceedings
Small
Reftype
DOI/URL
DOI
Groups
AbstractAbstract Hundreds of new electrochemical sensors are reported in literature every year. However, only a few of them makes it to the market. Manufacturability, or rather the lack of it, is the parameter that dictates if new sensing technologies will remain forever in the laboratory in which they are conceived. Inkjet printing is a low-cost and versatile technique that can facilitate the transfer of nanomaterial-based sensors to the market. Herein, an electroactive and self-assembling inkjet-printable ink based on protein-nanomaterial composites and exfoliated graphene is reported. The consensus tetratricopeptide proteins (CTPRs), used to formulate this ink, are engineered to template and coordinate electroactive metallic nanoclusters (NCs), and to self-assemble upon drying, forming stable films. The authors demonstrate that, by incorporating graphene in the ink formulation, it is possible to dramatically improve the electrocatalytic properties of the ink, obtaining an efficient hybrid material for hydrogen peroxide (H2O2) detection. Using this bio-ink, the authors manufactured disposable and environmentally sustainable electrochemical paper-based analytical devices (ePADs) to detect H2O2, outperforming commercial screen-printed platforms. Furthermore, it is demonstrated that oxidoreductase enzymes can be included in the formulation, to fully inkjet-print enzymatic amperometric biosensors ready to use.
AUTHOR
Title
Remodeling arteries: studying the mechanical properties of 3D-bioprinted hybrid photoresponsive materials
[Abstract]
Year
2023
Journal/Proceedings
J. Mater. Chem. B
Reftype
DOI/URL
DOI
Groups
Abstract3D-printed cell models are currently in the spotlight of medical research. Whilst significant advances have been made{,} there are still aspects that require attention to achieve more realistic models which faithfully represent the in vivo environment. In this work we describe the production of an artery model with cyclic expansive properties{,} capable of mimicking the different physical forces and stress factors that cells experience in physiological conditions. The artery wall components are reproduced using 3D printing of thermoresponsive polymers with inorganic nanoparticles (NPs) representing the outer tunica adventitia{,} smooth muscle cells embedded in extracellular matrix representing the tunica media{,} and finally a monolayer of endothelial cells as the tunica intima. Cyclic expansion can be induced thanks to the inclusion of photo-responsive plasmonic NPs embedded within the thermoresponsive ink composition{,} resulting in changes in the thermoresponsive polymer hydration state and hence volume{,} in a stimulated on–off manner. By changing the thermoresponsive polymer composition{,} the transition temperature and pulsatility can be efficiently tuned. We show the direct effect of cyclic expansion and contraction on the overlying cell layers by analyzing transcriptional changes in mechanoresponsive mesenchymal genes associated with such microenvironmental physical cues. The technique described herein involving stimuli-responsive 3D printed tissue constructs{,} also described as four- dimensional (4D) printing{,} offers a novel approach for the production of dynamic biomodels.
AUTHOR
Year
2021
Journal/Proceedings
Advanced Functional Materials
Reftype
DOI/URL
DOI
Groups
AbstractAbstract With the advent of flexible electronics, the old fashioned and conventional solid-state technology will be replaced by conductive inks combined with low-cost printing techniques. Graphene is an ideal candidate to produce conductive inks, due to its excellent conductivity and zero bandgap. The possibility to chemically modify graphene with active molecules opens up the field of responsive conductive inks. Herein, a bioresponsive, electroactive, and inkjet-printable graphene ink is presented. The ink is based on graphene chemically modified with selected enzymes and an electrochemical mediator, to transduce the products of the enzymatic reaction into an electron flow, proportional to the analyte concentration. A water-based formulation is engineered to be respectful with the enzymatic activity while matching the stringent requirements of inkjet printing. The efficient electrochemical performance of the ink, as well as a proof-of-concept application in biosensing, is demonstrated. The versatility of the system is demonstrated by modifying graphene with various oxidoreductases, obtaining inks with selectivity toward glucose, lactate, methanol, and ethanol.
AUTHOR
Title
Preventing Memory Effects in Surface-Enhanced Raman Scattering Substrates by Polymer Coating and Laser-Activated Deprotection
[Abstract]
Year
2021
Journal/Proceedings
ACS Nano
Reftype
DOI/URL
DOI
Groups
AbstractThe development of continuous monitoring systems requires in situ sensors that are capable of screening multiple chemical species and providing real-time information. Such in situ measurements, in which the sample is analyzed at the point of interest, are hindered by underlying problems derived from the recording of successive measurements within complex environments. In this context, surface-enhanced Raman scattering (SERS) spectroscopy appears as a noninvasive technology with the ability of identifying low concentrations of chemical species as well as resolving dynamic processes under different conditions. To this aim, the technique requires the use of a plasmonic substrate, typically made of nanostructured metals such as gold or silver, to enhance the Raman signal of adsorbed molecules (the analyte). However, a common source of uncertainty in real-time SERS measurements originates from the irreversible adsorption of (analyte) molecules onto the plasmonic substrate, which may interfere in subsequent measurements. This so-called “SERS memory effect” leads to measurements that do not accurately reflect varying conditions of the sample over time. We introduce herein the design of plasmonic substrates involving a nonpermeable poly(lactic-co-glycolic acid) (PLGA) thin layer on top of the plasmonic nanostructure, toward controlling the adsorption of molecules at different times. The polymeric layer can be locally degraded by irradiation with the same laser used for SERS measurements (albeit at a higher fluence), thereby creating a micrometer-sized window on the plasmonic substrate available to molecules present in solution at a selected measurement time. Using SERS substrates coated with such thermolabile polymer layers, we demonstrate the possibility of performing over 10,000 consecutive measurements per substrate as well as accurate continuous monitoring of analytes in microfluidic channels and biological systems. The development of continuous monitoring systems requires in situ sensors that are capable of screening multiple chemical species and providing real-time information. Such in situ measurements, in which the sample is analyzed at the point of interest, are hindered by underlying problems derived from the recording of successive measurements within complex environments. In this context, surface-enhanced Raman scattering (SERS) spectroscopy appears as a noninvasive technology with the ability of identifying low concentrations of chemical species as well as resolving dynamic processes under different conditions. To this aim, the technique requires the use of a plasmonic substrate, typically made of nanostructured metals such as gold or silver, to enhance the Raman signal of adsorbed molecules (the analyte). However, a common source of uncertainty in real-time SERS measurements originates from the irreversible adsorption of (analyte) molecules onto the plasmonic substrate, which may interfere in subsequent measurements. This so-called “SERS memory effect” leads to measurements that do not accurately reflect varying conditions of the sample over time. We introduce herein the design of plasmonic substrates involving a nonpermeable poly(lactic-co-glycolic acid) (PLGA) thin layer on top of the plasmonic nanostructure, toward controlling the adsorption of molecules at different times. The polymeric layer can be locally degraded by irradiation with the same laser used for SERS measurements (albeit at a higher fluence), thereby creating a micrometer-sized window on the plasmonic substrate available to molecules present in solution at a selected measurement time. Using SERS substrates coated with such thermolabile polymer layers, we demonstrate the possibility of performing over 10,000 consecutive measurements per substrate as well as accurate continuous monitoring of analytes in microfluidic channels and biological systems.
AUTHOR
Year
2020
Journal/Proceedings
Advanced Functional Materials
Reftype
DOI/URL
DOI
Groups
AbstractAbstract 3D printing strategies have acquired great relevance toward the design of 3D scaffolds with precise macroporous structures, for supported mammalian cell growth. Despite advances in 3D model designs, there is still a shortage of detection tools to precisely monitor in situ cell behavior in 3D, thereby allowing a better understanding of the progression of diseases or to test the efficacy of drugs in a more realistic microenvironment. Even if the number of available inks has exponentially increased, they do not necessarily offer the required functionalities to be used as internal sensors. Herein the potential of surface-enhanced Raman scattering (SERS) spectroscopy for the detection of biorelevant analytes within a plasmonic hydrogel-based, 3D-printed scaffold is demonstrated. Such SERS-active scaffolds allow for the 3D detection of model molecules, such as 4-mercaptobenzoic acid. Flexibility in the choice of plasmonic nanoparticles is demonstrated through the use of gold nanoparticles with different morphologies, gold nanorods showing the best balance between SERS enhancement and scaffold transparency. Detection of the biomarker adenosine is also demonstrated as a proof-of-concept toward the use of these plasmonic scaffolds for SERS sensing of cell-secreted molecules over extended periods of time.
AUTHOR
Year
2020
Journal/Proceedings
Advanced Functional Materials
Reftype
DOI/URL
DOI
Groups
AbstractAbstract The composition and intercellular interactions of tumor cells in the tissues dictate the biochemical and metabolic properties of the tumor microenvironment. The metabolic rewiring has a profound impact on the properties of the microenvironment, to an extent that monitoring such perturbations could harbor diagnostic and therapeutic relevance. A growing interest in these phenomena has inspired the development of novel technologies with sufficient sensitivity and resolution to monitor metabolic alterations in the tumor microenvironment. In this context, surface-enhanced Raman scattering (SERS) can be used for the label-free detection and imaging of diverse molecules of interest among extracellular components. Herein, the application of nanostructured plasmonic substrates comprising Au nanoparticles, self-assembled as ordered superlattices, to the precise SERS detection of selected tumor metabolites, is presented. The potential of this technology is first demonstrated through the analysis of kynurenine, a secreted immunomodulatory derivative of the tumor metabolism and the related molecules tryptophan and purine derivatives. SERS facilitates the unambiguous identification of trace metabolites and allows the multiplex detection of their characteristic fingerprints under different conditions. Finally, the effective plasmonic SERS substrate is combined with a hydrogel-based three-dimensional cancer model, which recreates the tumor microenvironment, for the real-time imaging of metabolite alterations and cytotoxic effects on tumor cells.