journal article·2024-08Open access

Strategies of functionalized GelMA-based bioinks for bone regeneration: Recent advances and future perspectives

Yaru Zhu, Xingge Yu, Hao Liu, Junjun Li, Mazaher Gholipourmalekabadi, Kaili Lin, Changyong Yuan, Penglai Wang

Abstract

Gelatin methacryloyl (GelMA) hydrogels is a widely used bioink because of its good biological properties and tunable physicochemical properties, which has been widely used in a variety of tissue engineering and tissue regeneration. However, pure GelMA is limited by the weak mechanical strength and the lack of continuous osteogenic induction environment, which is difficult to meet the needs of bone repair. Moreover, GelMA hydrogels are unable to respond to complex stimuli and therefore are unable to adapt to physiological and pathological microenvironments. This review focused on the functionalization strategies of GelMA hydrogel based bioinks for bone regeneration. The synthesis process of GelMA hydrogel was described in details, and various functional methods to meet the requirements of bone regeneration, including mechanical strength, porosity, vascularization, osteogenic differentiation, and immunoregulation for patient specific repair, etc. In addition, the response strategies of smart GelMA-based bioinks to external physical stimulation and internal pathological microenvironment stimulation, as well as the functionalization strategies of GelMA hydrogel to achieve both disease treatment and bone regeneration in the presence of various common diseases (such as inflammation, infection, tumor) are also briefly reviewed. Finally, we emphasized the current challenges and possible exploration directions of GelMA-based bioinks for bone regeneration.
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Research context

OpenAlex topics: 3D Printing in Biomedical Research · Innovative Microfluidic and Catalytic Techniques Innovation · Biomedical and Engineering Education

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (100+)

Show source-provided references
1. A partially demineralized allogeneic bone graft: in vitro osteogenic potential and preclinical evaluation in two different intramembranous bone healing models10.1038/s41598-021-84039-6 ↗
2. Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone
3. Advances on bone substitutes through 3D bioprinting10.3390/ijms21197012 ↗
4. Design and optimization of a novel bio-loom to weave melt-spun absorbable polymers for bone tissue engineering10.1002/jbm.b.33700 ↗
5. Advances in 3D printing of composite scaffolds for the repairment of bone tissue associated defects10.1002/btpr.3234 ↗
6. 3D bioprinting and the current applications in tissue engineering10.1002/biot.201600734 ↗
7. Development of 3D bioprinting: from printing methods to biomedical applications
8. Advanced strategies in the application of gelatin-based bioink for extrusion bioprinting10.1007/s42242-023-00236-4 ↗
9. Bioink Formulations for bone tissue regeneration
10. 3D bioprinting of human tissues: biofabrication, bioinks, and bioreactors10.3390/ijms22083971 ↗
11. GelMA-based bioactive hydrogel scaffolds with multiple bone defect repair functions: therapeutic strategies and recent advances10.1186/s40824-023-00422-6 ↗
12. Synthesis and properties of gelatin methacryloyl (GelMA) hydrogels and their recent applications in load-bearing tissue10.3390/polym10111290 ↗
13. 3D printed microchannel networks to direct vascularisation during endochondral bone repair10.1016/j.biomaterials.2018.01.057 ↗
14. Injectable stem cell‐laden photocrosslinkable microspheres fabricated using microfluidics for rapid generation of osteogenic tissue constructs10.1002/adfm.201504943 ↗
15. Bioprinted osteogenic and vasculogenic patterns for engineering 3D bone tissue10.1002/adhm.201700015 ↗
16. Structural and rheological properties of methacrylamide modified gelatin hydrogels10.1021/bm990017d ↗
17. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels10.1016/j.biomaterials.2015.08.045 ↗
18. 3D-Printed gelatin methacryloyl-based scaffolds with potential application in tissue engineering10.3390/polym13050727 ↗
19. Comparison of photo cross linkable gelatin derivatives and initiators for three-dimensional extrusion bioprinting10.1021/acs.biomac.9b01204 ↗
20. Designing gelatin methacryloyl (GelMA)‐Based bioinks for visible light stereolithographic 3D biofabrication10.1002/mabi.202170001 ↗
21. Martineau
22. Efficient and controllable synthesis of highly substituted gelatin methacrylamide for mechanically stiff hydrogels10.1039/C5RA22028A ↗
23. Systematic optimization of visible light-induced crosslinking conditions of gelatin methacryloyl (GelMA)10.1038/s41598-021-02830-x ↗
24. Reversible physical crosslinking strategy with optimal temperature for 3D bioprinting of human chondrocyte-laden gelatin methacryloyl bioink10.1177/0885328218805864 ↗
25. Role of temperature on bio-printability of gelatin methacryloyl bioink in two-step cross-linking strategy for tissue engineering applications
26. 3D bioprinting of methylcellulose/gelatin-methacryloyl (MC/GelMA) bioink with high shape integrity10.1021/acsabm.0c00169 ↗
27. 3D bioprinting of low-concentration cell-laden gelatin methacrylate (GelMA) bioinks with a two-step cross-linking strategy10.1021/acsami.7b16059 ↗
28. Printability and bio-functionality of a shear thinning methacrylated xanthan–gelatin composite bioink10.1088/1758-5090/abec2d ↗
29. Assessment of naturally sourced mineral clays for the 3D printing of biopolymer-based nanocomposite inks10.3390/nano11030703 ↗
30. 3D printing of complex GelMA-based scaffolds with nanoclay10.1088/1758-5090/ab0cf6 ↗
31. Facile extrusion 3D printing of gelatine methacrylate/Laponite nanocomposite hydrogel with high concentration nanoclay for bone tissue regeneration10.1016/j.ijbiomac.2021.07.199 ↗
32. Extrusion bioprinting of elastin‐containing bioactive double‐network tough hydrogels for complex elastic tissue regeneration10.1002/agt2.477 ↗
33. Hydrogel bioink reinforcement for additive manufacturing: a focused review of emerging strategies10.1002/adma.201902026 ↗
34. Carbon nanotube reinforced hybrid microgels as scaffold materials for cell encapsulation10.1021/nn203711s ↗
35. Mechanically reinforced injectable bioactive nanocomposite hydrogels for in-situ bone regeneration10.1016/j.cej.2021.132799 ↗
36. Osteoimmunomodulatory bioinks for 3D bioprinting achieve complete regeneration of critical-sized bone defects10.1016/j.compositesb.2024.111256 ↗
37. Enhanced electroactivity, mechanical properties, and printability through the addition of graphene oxide to photo-cross-linkable gelatin methacryloyl hydrogel10.1021/acsbiomaterials.0c01734 ↗
38. Cell-laden microengineered and mechanically tunable hybrid hydrogels of gelatin and graphene oxide10.1002/adma.201301082 ↗
39. Enhancement of properties of a cell-laden GelMA hydrogel-based bioink via calcium phosphate phase transition10.1088/1758-5090/ad05e2 ↗
40. Hydroxyapatite-incorporated composite gels improve mechanical properties and bioactivity of bone scaffolds10.1002/mabi.202000176 ↗
41. Sequentially-crosslinked biomimetic bioactive glass/gelatin methacryloyl composites hydrogels for bone regeneration10.1016/j.msec.2018.03.029 ↗
42. Controlling adult stem cell behavior using nanodiamond-reinforced hydrogel: implication in bone regeneration therapy10.1038/s41598-017-06028-y ↗
43. 3D printed hybrid bone constructs of PCL and dental pulp stem cells loaded GelMA10.1002/jbm.a.37235 ↗
44. Hybrid biofabrication of 3D osteoconductive constructs comprising Mg-based nanocomposites and cell-laden bioinks for bone repair10.1016/j.bone.2021.116198 ↗
45. Hybrid printing using cellulose nanocrystals reinforced GelMA/HAMA hydrogels for improved structural integration10.1002/adhm.202001410 ↗
46. Interpenetrating polymer network hydrogels composed of chitosan and photocrosslinkable gelatin with enhanced mechanical properties for tissue engineering10.1016/j.msec.2018.07.016 ↗
47. Affinity-bound growth factor within sulfated interpenetrating network bioinks for bioprinting cartilaginous tissues10.1016/j.actbio.2021.04.016 ↗
48. GelMa/PEGDA containing graphene oxide as an IPN hydrogel with superior mechanical performance
49. Highly methacrylated gelatin bioink for bone tissue engineering10.1021/acsbiomaterials.8b00778 ↗
50. Osteochondral regeneration with 3D‐printed biodegradable high‐strength supramolecular polymer reinforced‐gelatin hydrogel scaffolds10.1002/advs.201900867 ↗
51. Molecularly cleavable bioinks facilitate high-performance digital light processing-based bioprinting of functional volumetric soft tissues10.1038/s41467-022-31002-2 ↗
52. Bioresorbability, porosity and mechanical strength of bone substitutes: what is optimal for bone regeneration?10.1016/j.injury.2011.06.008 ↗
53. Effects of Irgacure 2959 and lithium phenyl-2,4,6-trimethylbenzoylphosphinate on cell viability, physical properties, and microstructure in 3D bioprinting of vascular-like constructs10.1088/1748-605X/ab954e ↗
54. Gelatin methacrylate scaffold for bone tissue engineering: the influence of polymer concentration10.1002/jbm.a.36226 ↗
55. Effect of freezing process on the microstructure of gelatin methacryloyl hydrogels
56. Aqueous two‐phase emulsion bioink‐enabled 3D bioprinting of porous hydrogels
57. Dynamic mechanics-modulated hydrogels to regulate the differentiation of stem-cell spheroids in soft microniches and modeling of the nonlinear behavior10.1002/smll.201901920 ↗
58. Adipose tissue-derived stromal cells alter the mechanical stability and viscoelastic properties of gelatine methacryloyl hydrogels10.3390/ijms221810153 ↗
59. Gelatin-methacryloyl (GelMA) formulated with human platelet lysate supports mesenchymal stem cell proliferation and differentiation and enhances the hydrogel's mechanical properties10.3390/bioengineering6030076 ↗
60. 3D-printed gelatin methacrylate (GelMA)/silanated silica scaffold assisted by two-stage cooling system for hard tissue regeneration10.1093/rb/rbab001 ↗
61. Enhanced electroactivity, mechanical properties, and printability through the addition of graphene oxide to photo-cross-linkable gelatin methacryloyl hydrogel10.1021/acsbiomaterials.0c01734 ↗
62. Hydroxyapatite‐incorporated composite gels improve mechanical properties and bioactivity of bone scaffolds10.1002/mabi.202000176 ↗
63. Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration10.1016/j.addr.2017.07.011 ↗
64. Hybrid printing using cellulose nanocrystals reinforced GelMA/HAMA hydrogels for improved structural integration10.1002/adhm.202001410 ↗
65. Highly methacrylated gelatin bioink for bone tissue engineering10.1021/acsbiomaterials.8b00778 ↗
66. Osteochondral regeneration with 3D-printed biodegradable high-strength supramolecular polymer reinforced-gelatin hydrogel scaffolds10.1002/advs.201900867 ↗
67. Self-healing hydrogels: the next paradigm shift in tissue engineering?
68. Hydrogels in regenerative medicine10.1002/adma.200802106 ↗
69. Supramolecular and dynamic covalent hydrogel scaffolds: from gelation chemistry to enhanced cell retention and cartilage regeneration10.1039/C9TB01698H ↗
70. 3D-printable self-healing and mechanically reinforced hydrogels with host–guest non-covalent interactions integrated into covalently linked networks10.1039/C8MH01208C ↗
71. A self-healing hydrogel and injectable cryogel of gelatin methacryloyl-polyurethane double network for 3D printing10.1016/j.actbio.2023.04.023 ↗
72. 3D-printable self-healing and mechanically reinforced hydrogels with host-guest non-covalent interactions integrated into covalently linked networks10.1039/C8MH01208C ↗
73. Alginate/gelatin-based hybrid hydrogels with function of injecting and encapsulating cells in situ10.1016/j.ijbiomac.2022.05.058 ↗
74. Three-dimensional printing self-healing dynamic/photocrosslinking gelatin-hyaluronic acid double-network hydrogel for tissue engineering10.1021/acsomega.2c00335 ↗
75. Assembling microgels via dynamic cross-linking reaction improves printability, microporosity, tissue-adhesion, and self-healing of microgel bioink for extrusion bioprinting10.1021/acsami.2c01295 ↗
76. Synergistic osteogenic and angiogenic effects of KP and QK peptides incorporated with an injectable and self-healing hydrogel for efficient bone regeneration
77. Glycerylphytate as an ionic crosslinker for 3D printing of multi-layered scaffolds with improved shape fidelity and biological features10.1039/C9BM01271K ↗
78. Bioprinting small-diameter vascular vessel with endothelium and smooth muscle by the approach of two-step crosslinking process10.1002/bit.28075 ↗
79. Supramolecular adhesive hydrogels for tissue engineering applications10.1021/acs.chemrev.1c00815 ↗
80. A novel double‐crosslinking‐double‐network design for injectable hydrogels with enhanced tissue adhesion and antibacterial capability for wound treatment
81. Hydrogen bonds autonomously powered gelatin methacrylate hydrogels with super-elasticity, self-heal and underwater self-adhesion for sutureless skin and stomach surgery and E-skin10.1016/j.biomaterials.2018.04.023 ↗
82. Highly adhesive, stretchable and breathable gelatin methacryloyl-based nanofibrous hydrogels for wound dressings10.1021/acsabm.1c01087 ↗
83. An adhesive and injectable nanocomposite hydrogel of thiolated gelatin/gelatin methacrylate/Laponite(R) as a potential surgical sealant10.1016/j.jcis.2019.12.048 ↗
84. An injectable hybrid gelatin methacryloyl (GelMA)/Phenyl isothiocyanate-modified gelatin (Gel-Phe) bioadhesive for oral/dental hemostasis applications10.3390/polym13142386 ↗
85. Biomimetic, stiff, and adhesive periosteum with osteogenic-angiogenic coupling effect for bone regeneration10.1002/smll.202006598 ↗
86. Challenges and strategies for in situ endothelialization and long-term lumen patency of vascular grafts
87. 3D biofabrication of vascular networks for tissue regeneration: a report on recent advances10.1016/j.jpha.2018.08.005 ↗
88. HIF-1alpha regulates osteogenesis of periosteum-derived stem cells under hypoxia conditions via modulating POSTN expression10.3389/fcell.2022.836285 ↗
89. Functional human vascular network generated in photocrosslinkable gelatin methacrylate hydrogels10.1002/adfm.201101662 ↗
90. Bioprinted osteogenic and vasculogenic patterns for engineering 3D bone tissue10.1002/adhm.201700015 ↗
91. Osteogenic and angiogenic tissue formation in high fidelity nanocomposite Laponite-gelatin bioinks10.1088/1758-5090/ab19fd ↗
92. Silicon-Phosphorus-nanosheets-integrated 3D-printable hydrogel as a bioactive and biodegradable scaffold for vascularized bone regeneration
93. Coaxial 3D bioprinting of tri‐polymer scaffolds to improve the osteogenic and vasculogenic potential of cells in co‐culture models10.1002/jbm.a.37354 ↗
94. Microsphere based scaffolds for bone regenerative applications10.1039/C4BM00161C ↗
95. Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration10.1038/s41413-021-00180-y ↗
96. BMSCs-laden mechanically reinforced bioactive sodium alginate composite hydrogel microspheres for minimally invasive bone repair10.1016/j.carbpol.2024.121933 ↗
97. Bone matrix production in hydroxyapatite-modified hydrogels suitable for bone bioprinting10.1088/1758-5090/aa91ec ↗
98. Enhancement of osteoporotic bone regeneration by strontium-substituted 45S5 bioglass via time-dependent modulation of autophagy and the Akt/mTOR signaling pathway10.1039/D0TB02991B ↗
99. Bone marrow stromal cells stimulated by strontium-substituted calcium silicate ceramics: release of exosomal miR-146a regulates osteogenesis and angiogenesis10.1016/j.actbio.2020.10.038 ↗
100. Lithium-containing bioactive glasses enhanced 3D-printed PLGA scaffolds for bone regeneration in diabetes10.1016/j.compositesb.2021.109550 ↗