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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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Samandari, M., Alipanah, F., Majidzadeh‐A, K., Álvarez, M. M., Santiago, G. T., & Tamayol, A. (2021) · Applied Physics Reviews · doi:10.1063/5.0040732 · Cited by 87
Self-citationSun, Y., Liu, X., Zhu, Y. M., Han, Y., Shen, J., Bao, B., Gao, T., Lin, J., Huang, T., Xu, J., et al. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c16300 · Cited by 86
Niu, Y., Li, Q., Xie, R., Liu, S., Wang, R., Xing, P., Shi, Y., Wang, Y., Dong, L., & Wang, C. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.05.042 · Cited by 86
Zhang, D., Fu, Y., Huang, L., Zhang, Y., Ren, B., Zhong, M., Yang, J., & Zheng, J. (2018) · Journal of Materials Chemistry B · doi:10.1039/c7tb03018e · Cited by 85
Zhang, Q., Qi, C., Wang, H., Xiao, X., Zhuang, Y., Gu, S., Zhou, Y., Wang, L., Yang, H., & Xu, W. (2019) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2019.115304 · Cited by 85
Nazir, F., Ashraf, I., Iqbal, M., Ahmad, T., & Anjum, S. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.06.112 · Cited by 85
The effects of surface topography modification on hydrogel properties
Cui, L., Yao, Y., & Yim, E. K. F. (2021) · APL Bioengineering · doi:10.1063/5.0046076 · Cited by 91
Xiong, Y., Xu, Y., Fei, Z., Hu, Y., Zhao, J., Liu, Z., Zhai, Q., Qi, S., Zhang, Z., & Chen, L. (2022) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10373 · Cited by 85
“cross-linking network hydrogel was formed through mixing the GelMA solution and the HA-E solution under UV-light irradiation.(32) Figure S3B displayed the image appearance of the GelMA/HA-E”
MethodChen, H., Fan, L., Peng, N., Yin, Y., Mu, D., Wang, J., Meng, R., & Xie, J. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.2c05352 · Cited by 85
Shriky, B., Babenko, M., & Whiteside, B. R. (2023) · Gels · doi:10.3390/gels9100806 · Cited by 85
“They reported that SN MNs reduced liver bleeding by approximately 92%, and they were found to degrade in vivo after weeks without any signs of major inflammation [153].”
BackgroundJia, X., Fan, X., Chen, C., Lu, Q., Zhou, H., Zhao, Y., Wang, X., Han, S., Ouyang, L., Yan, H., et al. (2024) · Biomacromolecules · doi:10.1021/acs.biomac.3c01021 · Cited by 90
Xu, H., Che, Y., Zhou, R., Wang, L., Huang, J., Kong, W., Liu, C., Guo, L., Tang, Y., Wang, X., et al. (2024) · Chemical Engineering Journal · doi:10.1016/j.cej.2024.153803 · Cited by 88
Visible light crosslinkable human hair keratin hydrogels
Yue, K., Liu, Y., Byambaa, B., Singh, V., Liu, W. H., Li, X., Sun, Y., Zhang, Y. S., Tamayol, A., Zhang, P., et al. (2017) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10077 · Cited by 85
Self-citationGuo, G., Jin, L., Jin, W., Chen, L., Yang, L., & Wang, Y. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.10.017 · Cited by 84
A gelatin hydrogel to study endometrial angiogenesis and trophoblast invasion
Zambuto, S. G., Clancy, K. B. H., & Harley, B. A. C. (2019) · Interface Focus · doi:10.1098/rsfs.2019.0016 · Cited by 83
“We further characterized our library of hydrogels by quantifying the mass swelling ratio, an indication of the degree of crosslinking in the hydrogel [27, 47].”
BackgroundMamidi, N., González-Ortiz, A., Romo‐López, I., & Barrera, E. V. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11120621 · Cited by 84
“Besides, hydrogels are used in cell-matrix, 3D culturing cell-cell interactions, cellular proliferation, differentiation, and migration [4,5].”
MethodGelatin Matrices for Growth Factor Sequestration
Buie, T., McCune, J. T., & Cosgriff‐Hernandez, E. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2019.12.005 · Cited by 84
Zheng, Y., Wu, G., Chen, L., Zhang, Y., Luo, Y., Zheng, Y., Hu, F., Forouzanfar, T., Lin, H., & Liu, B. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.08.026 · Cited by 84
3D printed hybrid bone constructs of PCL and dental pulp stem cells loaded GelMA
Büyüksungur, S., Hasırcı, V., & Hasırcı, N. (2021) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37235 · Cited by 84
Kushibiki, T., Mayumi, Y., Nakayama, E., Azuma, R., Ojima, K., Horiguchi, A., & Ishihara, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-02589-1 · Cited by 86
Ataie, Z., Kheirabadi, S., Zhang, J. W., Kedzierski, A., Petrosky, C., Jiang, R., Vollberg, C., & Sheikhi, A. (2022) · Small · doi:10.1002/smll.202202390 · Cited by 85
Li, S., Li, X., Xu, Y., Fan, C., Li, Z. A., Zheng, L., Luo, B., Li, Z., Lin, B., Zha, Z., et al. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.09.012 · Cited by 86
Advances of naturally derived biomedical polymers in tissue engineering
Hu, T., Fang, J., Shen, Y., Li, M., Wang, B., Xu, Z., & Hu, W. (2024) · Frontiers in Chemistry · doi:10.3389/fchem.2024.1469183 · Cited by 93
Bioinspired Hydrogels to Engineer Cancer Microenvironments
Park, K. M., Lewis, D. M., & Gerecht, S. (2017) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071516-044619 · Cited by 85
Liu, J., Tagami, T., & Ozeki, T. (2020) · Marine Drugs · doi:10.3390/md18060325 · Cited by 83
“The reaction scheme was prepared in previous studies [20,21].”
MethodChen, Z., & Lv, Y. (2022) · Composites Part B Engineering · doi:10.1016/j.compositesb.2022.110162 · Cited by 83
Zheng, Y., Pan, C., Xu, P., & Liu, K. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02315-9 · Cited by 96
“…hydrogel designed by Zhu et al., the good elasticity of SFMA compensates for the low mechanical modulus and limited pore size and porosity of GelMA [155], whereas the inter-penetrating polymer network formed by the combination of GelMA and SFMA further strengthens the mechanical properties of the…”
BackgroundSelf-Powered Thermoelectric Hydrogels Accelerate Wound Healing
Qin, Y., Jia, S., Shi, X., Gao, S., Zhao, J., Ma, H., Wei, Y., Huang, Q., Yang, L., Chen, Z., et al. (2025) · ACS Nano · doi:10.1021/acsnano.5c01742 · Cited by 83
Integrated cancer tissue engineering models for precision medicine
Bregenzer, M. E., Horst, E. N., Mehta, P., Novak, C. M., Raghavan, S. A., Snyder, C. S., & Mehta, G. (2019) · PLoS ONE · doi:10.1371/journal.pone.0216564 · Cited by 84
“Natural Hydrogels[47] Inherently Interactive Matrigel[48–50] Collagen [37,49,51] Gelatin[52,53] Hyaluronic acid [54] Chitosan[55] Inherently Inert Alginate[56] Agarose[39] Dextran[57] • Biocompatible • Low immune response • Innate bioactive motifs • Batch-to-batch variability • Poor mechanical tunability • Extraneous…”
BackgroundSynchronous 3D Bioprinting of Large‐Scale Cell‐Laden Constructs with Nutrient Networks
Shao, L., Gao, Q., Xie, C., Fu, J., Xiang, M., & He, Y. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201901142 · Cited by 83
Gelatin Methacryloyl–Riboflavin (GelMA–RF) Hydrogels for Bone Regeneration
Goto, R., Nishida, E., Kobayashi, S., Aino, M., Ohno, T., Iwamura, Y., Kikuchi, T., Hayashi, J., Yamamoto, G., Asakura, M., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041635 · Cited by 82
“The radical polymerization of GelMA hydrogel is generally initiated by exposure to UV light in the presence of a photoinitiator [7].”
BackgroundShi, Z., Zhong, Q., Chen, Y., Gao, J., Pan, X., Lian, Q., Chen, R., Wang, P., Wang, J., Shi, Z., et al. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s321387 · Cited by 82
“Specifically, GelMA has been widely used in tissue engineering with confirmed excellent biosafety.(57) HAP is the most abundant mineral in natural human bone and has also been widely used as a part of bone graft materials.”
BackgroundGao, Y., Wang, S., Shi, B., Wang, Y., Chen, Y., Wang, X., Lee, E., & Jiang, H. B. (2022) · Polymers · doi:10.3390/polym14050871 · Cited by 82
“prepared a gelatin methacrylamine (GelMA)/poly (ethylene glycol) diacrylate (PEGDA) fiber membrane, a bilayer structure with fiber nanostructure and hydrogel properties, through electrostatic spinning and photocrosslinking [72].”
MethodFunctional biomaterials for tendon/ligament repair and regeneration
Tang, Y., Wang, Z., Xiang, L., Zhao, Z., & Cui, W. (2022) · Regenerative Biomaterials · doi:10.1093/rb/rbac062 · Cited by 91
“Hydrogels can be combined with growth factors, cells and drugs and have been widely used for drug delivery, wound treatment and cell culture [128].”
BackgroundZhang, Q., Yang, G., Li, X., Dong, G., Su, W., Cui, M. J., Wang, Z. G., Liu, M., Zhou, Z., & Zhang, X. (2022) · ACS Nano · doi:10.1021/acsnano.2c10404 · Cited by 81
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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