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Advances in GelMA Hydrogel-Enabled Angiogenic-Osteogenic Coupling: From Structural Programming to Exogenous Cue
Chenyujun Hu1,2,3,4, Meng Zhang1,2,3,4, Haoran Jiang1,2,3,4
1Department of Orthopedics and Trauma, Peking University People's Hospital, Beijing 100044, China.
Journal of Functional Biomaterials
|June 25, 2026
Summary
Gelatin methacryloyl (GelMA) hydrogels show promise for bone regeneration by enhancing vascularization. Strategies focus on material design, bioactive delivery, and responsive systems, with exogenous delivery currently leading in preclinical support.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Tissue Engineering
Background:
- Vascular-osteogenic coupling is crucial for bone regeneration but impaired in pathological conditions.
- Gelatin methacryloyl (GelMA) hydrogels are versatile platforms for vascularized bone regeneration due to their bioactivity and tunable properties.
Purpose of the Study:
- To review and synthesize GelMA-based strategies for vascularized bone regeneration from a vascular-osteogenic coupling perspective.
- To categorize and compare existing GelMA approaches based on evidence level, reproducibility, and translational potential.
Main Methods:
- Categorization of GelMA strategies into intrinsic material design, exogenous bioactive delivery, and smart responsive systems.
- Analysis of each category regarding vascular ingrowth, enhancement of vascularization, and microenvironment recapitulation.
- Comparative assessment of strategies' evidence level, reproducibility, and translational potential.
Main Results:
- Exogenous delivery systems demonstrate strong preclinical support but face challenges in standardization and safety.
- Intrinsic material programming is less studied but offers potential for manufacturing consistency and translation.
- Stimuli-responsive systems are mostly in early-stage research (small-animal/proof-of-concept).
Conclusions:
- Future GelMA systems should prioritize predictability, reproducibility, and clinical feasibility over functional complexity.
- Compositionally defined and structurally controllable GelMA composites integrating vascular regulation and mechanical support offer a promising path for bone regeneration.
