Main Article Content

Abstract

Articular cartilage, a tissue that is particularly known for its self-repairing
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

GelMA Hydrogel Characterization Cartilage tissue applications

Article Details

References

  1. Sophia Fox AJ, Bedi A, Rodeo S a. The Basic Science of Articular Cartilage: Structure, Composition, and Function.
  2. Sport
  3. A Multidiscip Approach [Internet]. 2009 Nov 1;1(6):461–8. Available from:
  4. http://sph.sagepub.com/lookup/doi/10.1177/1941738109350438
  5. Danila MI. Biology of normal joint and evaluation of the joint including clinical, imaging, and pathologic evaluation.
  6. ;
  7. Wilson DABT-CVA, editor. Ultrasound: Musculoskeletal. In Saint Louis: W.B. Saunders; 2012. p. 830–5. Available
  8. from: https://www.sciencedirect.com/science/article/pii/B9781416099796008229
  9. Krakowski P, Rejniak A, Sobczyk J, Karpiński R. Cartilage integrity: A review of mechanical and frictional properties
  10. and repair approaches in osteoarthritis. In: Healthcare. MDPI; 2024. p. 1648.
  11. Leifer VP, Katz JN, Losina E. The burden of OA-health services and economics. Osteoarthr Cartil. 2022;30(1):10–6.
  12. Camp CL, Stuart MJ, Krych AJ. Current concepts of articular cartilage restoration techniques in the knee. Sports
  13. Health. 2014;6(3):265–73.
  14. Armiento AR, Alini M, Stoddart MJ. Articular fibrocartilage-Why does hyaline cartilage fail to repair? Adv Drug
  15. Deliv Rev. 2019;146:289–305.
  16. Rana D, Kumar TSS, Ramalingam M. Cell-Laden Hydrogels for Tissue Engineering. J Biomater Tissue Eng [Internet].
  17. ;4(7):507–35.
  18. Available
  19. from:
  20. &volume=4&issue=7&spage=507
  21. http://openurl.ingenta.com/content/xref?genre=article&issn=2157
  22. Jahani A, Nourbakhsh MS, Ebrahimzadeh MH, Mohammadi M, Yari D, Moradi A. Biomolecules-loading of 3D
  23. printed alginate-based scaffolds for cartilage tissue engineering applications: a review on current status and future
  24. prospective. Arch Bone Jt Surg. 2024;12(2):92.
  25. Hago EE, Xinsong L, Kai JJ, Levett PA, Melchels FPW, Schrobback K, et al. A New Route Toward IPN
  26. Photocrosslinked Alginate Hydrogels with Biodegradation Rates, Excellent Biocompatibility and Mechanical
  27. Properties.
  28. J Biomater Tissue Eng [Internet]. 2014;4(2):89–98. Available
  29. http://openurl.ingenta.com/content/xref?genre=article&issn=2157-9083&volume=4&issue=2&spage=89
  30. from: Puppi D, Chiellini F, Piras a. MM, Chiellini E. Polymeric materials for bone and cartilage repair. Prog Polym Sci
  31. [Internet]. 2010;35(4):403–40. Available from: http://www.sciencedirect.com/science/article/B6TX2-4Y8G5SJ
  32. /2/a189a4998515b1c2b49e2c5039b2364c
  33. Savsani K, Aitchison AH, Allen NB, Adams EA, Adams SB. The Use of Gelatin Methacrylate (GelMA) in Cartilage
  34. Tissue Engineering: A Comprehensive Review. Bioengineering. 2025;12(7):700.
  35. Shin H, Olsen BD, Khademhosseini A. The mechanical properties and cytotoxicity of cell-laden double-network
  36. hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules. Biomaterials. 2012;33(11):3143
  37. Occhetta P, Visone R, Russo L, Cipolla L, Moretti M, Rasponi M. VA-086 methacrylate gelatine photopolymerizable
  38. hydrogels: A parametric study for highly biocompatible 3D cell embedding. J Biomed Mater Res - Part A [Internet].
  39. Jun;103(6):2109–17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25294368
  40. Mishbak H, Caetano GF, Pereira RF, Bartolo PJ. Photocurable Crosslinked Sodium Alginate and Gelatin based
  41. hydrogels for articular cartilage applications. 2016;6.
  42. Bupphathong S, Quiroz C, Huang W, Chung P-F, Tao H-Y, Lin C-H. Gelatin methacrylate hydrogel for tissue
  43. engineering applications—a review on material modifications. Pharmaceuticals. 2022;15(2):171.
  44. Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and
  45. biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254–71.
  46. Kim Y-H, Dawson JI, Oreffo ROC, Tabata Y, Kumar D, Aparicio C, et al. Gelatin methacryloyl hydrogels for
  47. musculoskeletal tissue regeneration. Bioengineering. 2022;9(7):332.
  48. 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,
  49. and adipogenic differentiation of adipose tissue-derived stem cells cultured on soy protein–agarose scaffolds. Foods.
  50. ;13(14):2247.
  51. Asim S, Tabish TA, Liaqat U, Ozbolat IT, Rizwan M. Advances in gelatin bioinks to optimize bioprinted cell
  52. functions. Adv Healthc Mater. 2023;12(17):2203148.
  53. Guo A, Zhang S, Yang R, Sui C. Enhancing the mechanical strength of 3D printed GelMA for soft tissue engineering
  54. applications. Mater Today Bio. 2024;24:100939.
  55. Zhu M, Wang Y, Ferracci G, Zheng J, Cho N-J, Lee BH. Gelatin methacryloyl and its hydrogels with an exceptional
  56. degree of controllability and batch-to-batch consistency. Sci Rep. 2019;9(1):6863.
  57. Lee BH, Lum N, Seow LY, Lim PQ, Tan LP. Synthesis and characterization of types A and B gelatin methacryloyl
  58. for bioink applications. Materials (Basel). 2016;9(10):797.
  59. Iyer KS, Bao L, Zhai J, Jayachandran A, Luwor R, Li JJ, et al. Microgel-based bioink for extrusion-based 3D
  60. bioprinting and its applications in tissue engineering. Bioact Mater. 2025;48:273–93.
  61. Yin J, Yan M, Wang Y, Fu J, Suo H. 3D bioprinting of low-concentration cell-laden gelatin methacrylate (GelMA)
  62. bioinks with a two-step cross-linking strategy. ACS Appl Mater Interfaces. 2018;10(8):6849–57.
  63. Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A. Cell-laden microengineered gelatin
  64. methacrylate hydrogels. Biomaterials. 2010;31(21):5536–44.
  65. Schuurman W, Levett PA, Pot MW, van Weeren PR, Dhert WJA, Hutmacher DW, et al. Gelatin‐methacrylamide
  66. hydrogels as potential biomaterials for fabrication of tissue‐engineered cartilage constructs. Macromol Biosci.
  67. ;13(5):551–61.
  68. Mow VC, Kuei SC, Lai WM, Armstrong CG. Biphasic creep and stress relaxation of articular cartilage in compression:
  69. theory and experiments. J Biomech Eng. 1980;102(1):73–84.
  70. Beck EC, Barragan M, Tadros MH, Gehrke SH, Detamore MS. Approaching the compressive modulus of articular
  71. cartilage with a decellularized cartilage-based hydrogel. Acta Biomater [Internet]. 2015; Available from:
  72. http://dx.doi.org/10.1016/j.actbio.2016.04.019
  73. Annabi N, Tamayol A, Uquillas JA, Akbari M, Bertassoni LE, Cha C, et al. 25th anniversary article: Rational design
  74. and applications of hydrogels in regenerative medicine. Adv Mater [Internet]. 2014 Jan;26(1):85–124. Available from:
  75. http://doi.wiley.com/10.1002/adma.201303233
  76. Ostrovidov S, Salehi S, Costantini M, Suthiwanich K, Ebrahimi M, Sadeghian RB, et al. 3D bioprinting in skeletal
  77. muscle tissue engineering. Small. 2019;15(24):1805530.

Similar Articles

You may also start an advanced similarity search for this article.