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Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels
Open accessAbstract
Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics. Three dimensional (3D) GelMA hydrogels closely resemble some essential properties of native extracellular matrix (ECM) due to the presence of cell-attaching and matrix metalloproteinase responsive peptide motifs, which allow cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile from a processing perspective. It crosslinks when exposed to light irradiation to form hydrogels with tunable mechanical properties which mimic the native ECM. It can also be microfabricated using different methodologies including micromolding, photomasking, bioprinting, self-assembly, and microfluidic techniques to generate constructs with controlled architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to form networks with desired combined properties and characteristics for specific biological applications. Recent research has demonstrated the proficiency of GelMA-based hydrogels in a wide range of applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others. Other applications of GelMA hydrogels, besides tissue engineering, include fundamental single-single cell research, cell signaling, drug and gene delivery, and bio-sensing.
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“To this end, considerable efforts were made in developing hydrogel-based inks or printing techniques to enhance 3D stability and shape fidelity, such as printing multimaterial inks with combined nozzle system24, 25, photo-crosslinkable hydrogels17, 26, 27, adding viscosifiers28–30, or printing in sacrificial supporting materials31–33.”
From Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles (2023) · cites this paper as [17]
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“In this study, chondrocyte spheroids (chondro-spheroids) prepared using the hangingdrop method were loaded into cross-linkable gelatin methacrylate (GelMA)/hyaluronic acid methacrylate (HAMA) hybrid hydrogels [17,38], which proved to be suitable for chondrocytes.”
BackgroundMethodSmart biomaterial-based systems for intrinsic stimuli-responsive chronic wound management
Alves, P. M., Barrias, C. C., Gomes, P. A. C., & Martins, M. C. L. (2021) · Materials Today Chemistry · doi:10.1016/j.mtchem.2021.100623 · Cited by 48
Chansoria, P., Asif, S., Gupta, N. K., Piedrahita, J. A., & Shirwaiker, R. A. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202102351 · Cited by 43
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3D-Printed Hybrid Collagen/GelMA Hydrogels for Tissue Engineering Applications
Nagaraj, A., Etxabide, A., Naffa, R., Zidan, G., & Seyfoddin, A. (2022) · Biology · doi:10.3390/biology11111561 · Cited by 44
“The mixture was left at 50 °C for 3 h with continuous stirring to allow for the substitution reaction of the methacryloyl groups onto the amino acid residue’s amine and hydroxyl groups [54,61].”
BackgroundMethodInfluentialApplication of Hydrogels as Sustained-Release Drug Carriers in Bone Defect Repair
Feng, Y., Guo, W., Hu, L., Yi, X., & Tang, F. (2022) · Polymers · doi:10.3390/polym14224906 · Cited by 45
“Because of cell adhesion ability due to its rich RGD sequences [65] and many other advantages such as low price, good biocompatibility, degradability and weak immunogenicity, gelatin has been widely researched and applied in biomedicine, including contact lenses, artificial tendons, tissue engineering and drug deliver…”
BackgroundAn, C., Zhou, R., Zhang, H., Zhang, Y., Liu, W., Liu, J. S., Bao, B., Sun, K., Ren, C., Zhang, Y., et al. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.11.034 · Cited by 44
Current advancements in bio-ink technology for cartilage and bone tissue engineering
Badhe, R. V., Chatterjee, A., Bijukumar, D. R., & Mathew, M. T. (2023) · Bone · doi:10.1016/j.bone.2023.116746 · Cited by 44
Dong, Q., Yang, X., Liang, X., Liu, J., Wang, B., Zhao, Y., Huselstein, C., Feng, X., Tong, Z., & Chen, Y. (2023) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.3c02548 · Cited by 47
Photo-crosslinked bioactive BG/BMSCs@GelMA hydrogels for bone-defect repairs
Ai, Y., Dai, F., Li, W., Xu, F., Yang, H., Wu, J., Yang, K., Li, L., Ai, F., & Song, L. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100882 · Cited by 44
“GelMA prepared by the reaction of gelatin with MA contains arginine-glycine-aspartate (RGD) sequence and matrix metalloproteinase (MMP), which can promote cell adhesion, proliferation and differentiation [5].”
MethodMicrofluidic Bioprinting for Engineering Vascularized Tissues and Organoids
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Injectable alendronate-functionalized GelMA hydrogels for mineralization and osteogenesis
Liu, L., Li, X., Shi, X., & Wang, Y. (2018) · RSC Advances · doi:10.1039/c8ra03550d · Cited by 44
Zheng, J., Zhu, M., Ferracci, G., Cho, N., & Lee, B. H. (2018) · Macromolecular Chemistry and Physics · doi:10.1002/macp.201800266 · Cited by 44
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Hybrid Cornea: Cell Laden Hydrogel Incorporated Decellularized Matrix
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Injectable hydrogels for tendon and ligament tissue engineering
Liu, R., Zhang, S., & Chen, X. (2020) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.3078 · Cited by 44
“Gelatin methacryloyl (GelMA) hydrogels have some basic properties similar to those of natural ECM due to the presence of cell attachment and matrix metalloproteinase-reactive peptide motifs, all- owing cells to proliferate and spread in GelMA-based scaffolds (Yue et al., 2015).”
BackgroundAsgari, N., Bagheri, F., Eslaminejad, M. B., Ghanian, M. H., Sayahpour, F. A., & Ghafari, A. M. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01797-2 · Cited by 44
3D printing of chemical-empowered tendon stem/progenitor cells for functional tissue repair
Zhang, Y., Lei, T., Tang, C., Chen, Y., Liao, Y., Ju, W., Zhang, H., Zhou, B., Liang, R., Zhang, T., et al. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120722 · Cited by 44
Effect of Photoinitiator on Precursory Stability and Curing Depth of Thiol-Ene Clickable Gelatin
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Self‐Oxygenation of Tissues Orchestrates Full‐Thickness Vascularization of Living Implants
Farzin, A., Hassan, S., Teixeira, L. M., Gurian, M., Crispim, J. F., Manhas, V., Carlier, A., Bae, H., Geris, L., Noshadi, I., et al. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202100850 · Cited by 44
Computational Modeling and Experimental Characterization of Extrusion Printing into Suspension Baths
Prendergast, M. E., & Burdick, J. A. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202101679 · Cited by 44
Constructing biomimetic liver models through biomaterials and vasculature engineering
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“Gelatin Methacrylamide (GelMA) is a modified gelatin that crosslinks in seconds under UV light [133, 145].”
BackgroundEffect of Freezing Process on the Microstructure of Gelatin Methacryloyl Hydrogels
Liu, T., Zhang, Y., Sun, M., Jin, M., Xia, W., Yang, H., & Wang, T. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.810155 · Cited by 43
“GelMA hydrogels possess arginine-glycine-aspartic acid (RGD) peptide sequences and matrix metalloproteinase (MMP) sequences, which favor cell adhesion and remodeling (Yue et al., 2015; Sun et al., 2018; Basara et al., 2019).”
BackgroundApplications of Gelatin in Biosensors: Recent Trends and Progress
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Shape Fidelity Evaluation of Alginate-Based Hydrogels through Extrusion-Based Bioprinting
Temirel, M., Dabbagh, S. R., & Taşoğlu, S. (2022) · Journal of Functional Biomaterials · doi:10.3390/jfb13040225 · Cited by 43
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Gelatin methacryloyl and Laponite bioink for 3D bioprinted organotypic tumor modeling
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“Gelatin methacryloyl was synthesized as described in previous studies [39, 40].”
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CARDIOVASCULAR DISEASE, SIGNALING, GENE/CELL THERAPY AND ADVANCED NANOBIOMATERIALS
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The Role of Natural Hydrogels in Enhancing Wound Healing: From Biomaterials to Bioactive Therapies
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Metadata
- Authors
- Yue, K., Trujillo-de Santiago, G., Alvarez, M. M., Tamayol, A., Annabi, N., & Khademhosseini, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Annabi, Nasim
- Khademhosseini, Ali
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 73
- Pages
- 254-271
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC4610009
- OpenAlex
- W1120477740
- Semantic Scholar
- db0131b27b7eaf183c929a73ccd69d06de5cc188
- Cited by
- 3,146
- References
- 111
- Citations by year
- 2026: 433 · 2025: 464 · 2024: 394 · 2023: 430 · 2022: 347 · 2021: 314 · 2020: 243 · 2019: 213 · 2018: 137 · 2017: 106 · 2016: 60 · 2015: 3
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biomaterials (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Health and Medical Research Council
- National Science Foundation (EFRI-1240443)
- IMMODGEL (602694)
- National Institutes of Health (EB012597, AR057837, DE021468, HL099073, AI105024, AR063745)
- Tecnológico de Monterrey
- Consejo Nacional de Ciencia y Tecnología, México-CONACyT (262130)
- CONACyT-Sistema Nacional de Investigadores (26048)
- MIT International Science and Technology Initiatives (MISTI)
- Fundación México en Harvard
- CONACYT (234713)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- gelatin methacryloyl, GelMA hydrogel, hydrogel synthesis, photopolymerization, extracellular matrix mimics, cell adhesion, tissue engineering scaffolds, bone tissue engineering, cartilage tissue engineering, cardiac tissue engineering, vascular tissue engineering, bioprinting, microfabrication, hybrid hydrogels, carbon nanotubes, graphene oxide, drug delivery, gene delivery, biosensing
- MeSH terms
- Animals, Biocompatible Materials, Extracellular Matrix, Gelatin, Graphite, Humans, Methacrylates, Oxides, Polymers, Hydrogels, Amino Acid Motifs, Tissue Engineering, Nanotubes, Carbon, Microfluidics, Cell Proliferation, Mice, Tissue Scaffolds
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