Main Article Content
Abstract
deficiency, is a major challenge in regenerative medicine. Gelatin Methacrylate
(GelMA) is a multifunctional and biocompatible hydrogel, which has attracted
much attention as a potential scaffold material for cartilage tissue engineering.
This paper gives a detailed characterization of GelMA hydrogels with regard to
the effect of polymer concentration on their physicochemical and biological
properties. We performed an in-depth analysis of GelMA at concentrations of 5%,
10% and 15% (w/v) and their mechanical strength, swelling kinetics, degradation
rates and porous architecture. Additionally, we have synthesized and critically
reviewed optimal parameters for 3D bio-printing of constructs based on GelMA
for cartilage regeneration. Our results show that the mechanical properties are
significantly improved with an increase in the concentration of GelMA from 5%
to 15%, and the compressive modulus has been increased from 3.3 +- 0.5 kPa to
30.0 +- 4.0 kPa. This enhancement, however, comes with a decrease in porosity,
swelling ratio and degradation rate. While no one GelMA formulation reproduced
the mechanical properties of native articular cartilage, a 10% (w/v) concentration
of GelMA, with optimized 3D bioprinting parameters, appears to be a well
balanced formulation. It provides a good compromise between mechanical
stability and microenvironment that allows the viability, proliferation, and
chondrogenesis of cells. This critical review highlights the opportunities of the
GelMA as a highly tunable and promising platform in which effective and
clinically relevant cartilage repair and regeneration strategies can be developed.
Keywords
Article Details
Copyright (c) 2025 Hussein Mishbak, Mohammed A. Albadri, Mohammedsadiq A. Hasan

This work is licensed under a Creative Commons Attribution 4.0 International License.
References
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- http://sph.sagepub.com/lookup/doi/10.1177/1941738109350438
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- ;
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- from: https://www.sciencedirect.com/science/article/pii/B9781416099796008229
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- /2/a189a4998515b1c2b49e2c5039b2364c
- Savsani K, Aitchison AH, Allen NB, Adams EA, Adams SB. The Use of Gelatin Methacrylate (GelMA) in Cartilage
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- Shin H, Olsen BD, Khademhosseini A. The mechanical properties and cytotoxicity of cell-laden double-network
- hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules. Biomaterials. 2012;33(11):3143
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- engineering applications—a review on material modifications. Pharmaceuticals. 2022;15(2):171.
- Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and
- biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254–71.
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- musculoskeletal tissue regeneration. Bioengineering. 2022;9(7):332.
- Hong S-J, Kim D-H, Ryoo J-H, Park S-M, Kwon H-C, Keum D-H, et al. Influence of gelatin on adhesion, proliferation,
- and adipogenic differentiation of adipose tissue-derived stem cells cultured on soy protein–agarose scaffolds. Foods.
- ;13(14):2247.
- Asim S, Tabish TA, Liaqat U, Ozbolat IT, Rizwan M. Advances in gelatin bioinks to optimize bioprinted cell
- functions. Adv Healthc Mater. 2023;12(17):2203148.
- Guo A, Zhang S, Yang R, Sui C. Enhancing the mechanical strength of 3D printed GelMA for soft tissue engineering
- applications. Mater Today Bio. 2024;24:100939.
- Zhu M, Wang Y, Ferracci G, Zheng J, Cho N-J, Lee BH. Gelatin methacryloyl and its hydrogels with an exceptional
- degree of controllability and batch-to-batch consistency. Sci Rep. 2019;9(1):6863.
- Lee BH, Lum N, Seow LY, Lim PQ, Tan LP. Synthesis and characterization of types A and B gelatin methacryloyl
- for bioink applications. Materials (Basel). 2016;9(10):797.
- Iyer KS, Bao L, Zhai J, Jayachandran A, Luwor R, Li JJ, et al. Microgel-based bioink for extrusion-based 3D
- bioprinting and its applications in tissue engineering. Bioact Mater. 2025;48:273–93.
- Yin J, Yan M, Wang Y, Fu J, Suo H. 3D bioprinting of low-concentration cell-laden gelatin methacrylate (GelMA)
- bioinks with a two-step cross-linking strategy. ACS Appl Mater Interfaces. 2018;10(8):6849–57.
- Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A. Cell-laden microengineered gelatin
- methacrylate hydrogels. Biomaterials. 2010;31(21):5536–44.
- Schuurman W, Levett PA, Pot MW, van Weeren PR, Dhert WJA, Hutmacher DW, et al. Gelatin‐methacrylamide
- hydrogels as potential biomaterials for fabrication of tissue‐engineered cartilage constructs. Macromol Biosci.
- ;13(5):551–61.
- Mow VC, Kuei SC, Lai WM, Armstrong CG. Biphasic creep and stress relaxation of articular cartilage in compression:
- theory and experiments. J Biomech Eng. 1980;102(1):73–84.
- Beck EC, Barragan M, Tadros MH, Gehrke SH, Detamore MS. Approaching the compressive modulus of articular
- cartilage with a decellularized cartilage-based hydrogel. Acta Biomater [Internet]. 2015; Available from:
- http://dx.doi.org/10.1016/j.actbio.2016.04.019
- Annabi N, Tamayol A, Uquillas JA, Akbari M, Bertassoni LE, Cha C, et al. 25th anniversary article: Rational design
- and applications of hydrogels in regenerative medicine. Adv Mater [Internet]. 2014 Jan;26(1):85–124. Available from:
- http://doi.wiley.com/10.1002/adma.201303233
- Ostrovidov S, Salehi S, Costantini M, Suthiwanich K, Ebrahimi M, Sadeghian RB, et al. 3D bioprinting in skeletal
- muscle tissue engineering. Small. 2019;15(24):1805530.
References
Sophia Fox AJ, Bedi A, Rodeo S a. The Basic Science of Articular Cartilage: Structure, Composition, and Function.
Sport
A Multidiscip Approach [Internet]. 2009 Nov 1;1(6):461–8. Available from:
http://sph.sagepub.com/lookup/doi/10.1177/1941738109350438
Danila MI. Biology of normal joint and evaluation of the joint including clinical, imaging, and pathologic evaluation.
;
Wilson DABT-CVA, editor. Ultrasound: Musculoskeletal. In Saint Louis: W.B. Saunders; 2012. p. 830–5. Available
from: https://www.sciencedirect.com/science/article/pii/B9781416099796008229
Krakowski P, Rejniak A, Sobczyk J, Karpiński R. Cartilage integrity: A review of mechanical and frictional properties
and repair approaches in osteoarthritis. In: Healthcare. MDPI; 2024. p. 1648.
Leifer VP, Katz JN, Losina E. The burden of OA-health services and economics. Osteoarthr Cartil. 2022;30(1):10–6.
Camp CL, Stuart MJ, Krych AJ. Current concepts of articular cartilage restoration techniques in the knee. Sports
Health. 2014;6(3):265–73.
Armiento AR, Alini M, Stoddart MJ. Articular fibrocartilage-Why does hyaline cartilage fail to repair? Adv Drug
Deliv Rev. 2019;146:289–305.
Rana D, Kumar TSS, Ramalingam M. Cell-Laden Hydrogels for Tissue Engineering. J Biomater Tissue Eng [Internet].
;4(7):507–35.
Available
from:
&volume=4&issue=7&spage=507
http://openurl.ingenta.com/content/xref?genre=article&issn=2157
Jahani A, Nourbakhsh MS, Ebrahimzadeh MH, Mohammadi M, Yari D, Moradi A. Biomolecules-loading of 3D
printed alginate-based scaffolds for cartilage tissue engineering applications: a review on current status and future
prospective. Arch Bone Jt Surg. 2024;12(2):92.
Hago EE, Xinsong L, Kai JJ, Levett PA, Melchels FPW, Schrobback K, et al. A New Route Toward IPN
Photocrosslinked Alginate Hydrogels with Biodegradation Rates, Excellent Biocompatibility and Mechanical
Properties.
J Biomater Tissue Eng [Internet]. 2014;4(2):89–98. Available
http://openurl.ingenta.com/content/xref?genre=article&issn=2157-9083&volume=4&issue=2&spage=89
from: Puppi D, Chiellini F, Piras a. MM, Chiellini E. Polymeric materials for bone and cartilage repair. Prog Polym Sci
[Internet]. 2010;35(4):403–40. Available from: http://www.sciencedirect.com/science/article/B6TX2-4Y8G5SJ
/2/a189a4998515b1c2b49e2c5039b2364c
Savsani K, Aitchison AH, Allen NB, Adams EA, Adams SB. The Use of Gelatin Methacrylate (GelMA) in Cartilage
Tissue Engineering: A Comprehensive Review. Bioengineering. 2025;12(7):700.
Shin H, Olsen BD, Khademhosseini A. The mechanical properties and cytotoxicity of cell-laden double-network
hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules. Biomaterials. 2012;33(11):3143
Occhetta P, Visone R, Russo L, Cipolla L, Moretti M, Rasponi M. VA-086 methacrylate gelatine photopolymerizable
hydrogels: A parametric study for highly biocompatible 3D cell embedding. J Biomed Mater Res - Part A [Internet].
Jun;103(6):2109–17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25294368
Mishbak H, Caetano GF, Pereira RF, Bartolo PJ. Photocurable Crosslinked Sodium Alginate and Gelatin based
hydrogels for articular cartilage applications. 2016;6.
Bupphathong S, Quiroz C, Huang W, Chung P-F, Tao H-Y, Lin C-H. Gelatin methacrylate hydrogel for tissue
engineering applications—a review on material modifications. Pharmaceuticals. 2022;15(2):171.
Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and
biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254–71.
Kim Y-H, Dawson JI, Oreffo ROC, Tabata Y, Kumar D, Aparicio C, et al. Gelatin methacryloyl hydrogels for
musculoskeletal tissue regeneration. Bioengineering. 2022;9(7):332.
Hong S-J, Kim D-H, Ryoo J-H, Park S-M, Kwon H-C, Keum D-H, et al. Influence of gelatin on adhesion, proliferation,
and adipogenic differentiation of adipose tissue-derived stem cells cultured on soy protein–agarose scaffolds. Foods.
;13(14):2247.
Asim S, Tabish TA, Liaqat U, Ozbolat IT, Rizwan M. Advances in gelatin bioinks to optimize bioprinted cell
functions. Adv Healthc Mater. 2023;12(17):2203148.
Guo A, Zhang S, Yang R, Sui C. Enhancing the mechanical strength of 3D printed GelMA for soft tissue engineering
applications. Mater Today Bio. 2024;24:100939.
Zhu M, Wang Y, Ferracci G, Zheng J, Cho N-J, Lee BH. Gelatin methacryloyl and its hydrogels with an exceptional
degree of controllability and batch-to-batch consistency. Sci Rep. 2019;9(1):6863.
Lee BH, Lum N, Seow LY, Lim PQ, Tan LP. Synthesis and characterization of types A and B gelatin methacryloyl
for bioink applications. Materials (Basel). 2016;9(10):797.
Iyer KS, Bao L, Zhai J, Jayachandran A, Luwor R, Li JJ, et al. Microgel-based bioink for extrusion-based 3D
bioprinting and its applications in tissue engineering. Bioact Mater. 2025;48:273–93.
Yin J, Yan M, Wang Y, Fu J, Suo H. 3D bioprinting of low-concentration cell-laden gelatin methacrylate (GelMA)
bioinks with a two-step cross-linking strategy. ACS Appl Mater Interfaces. 2018;10(8):6849–57.
Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A. Cell-laden microengineered gelatin
methacrylate hydrogels. Biomaterials. 2010;31(21):5536–44.
Schuurman W, Levett PA, Pot MW, van Weeren PR, Dhert WJA, Hutmacher DW, et al. Gelatin‐methacrylamide
hydrogels as potential biomaterials for fabrication of tissue‐engineered cartilage constructs. Macromol Biosci.
;13(5):551–61.
Mow VC, Kuei SC, Lai WM, Armstrong CG. Biphasic creep and stress relaxation of articular cartilage in compression:
theory and experiments. J Biomech Eng. 1980;102(1):73–84.
Beck EC, Barragan M, Tadros MH, Gehrke SH, Detamore MS. Approaching the compressive modulus of articular
cartilage with a decellularized cartilage-based hydrogel. Acta Biomater [Internet]. 2015; Available from:
http://dx.doi.org/10.1016/j.actbio.2016.04.019
Annabi N, Tamayol A, Uquillas JA, Akbari M, Bertassoni LE, Cha C, et al. 25th anniversary article: Rational design
and applications of hydrogels in regenerative medicine. Adv Mater [Internet]. 2014 Jan;26(1):85–124. Available from:
http://doi.wiley.com/10.1002/adma.201303233
Ostrovidov S, Salehi S, Costantini M, Suthiwanich K, Ebrahimi M, Sadeghian RB, et al. 3D bioprinting in skeletal
muscle tissue engineering. Small. 2019;15(24):1805530.
