Size-Tunable Positively Charged Methacrylated Gelatin/Chitosan Composite Hydrogel Microspheres Promote Angiogenesis

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Vascular Biology

Background:

• Angiogenesis is crucial for tissue regeneration and treating diseases like organ damage and ischemia.
• Biomaterials that stimulate endogenous vascularization are vital for regenerative medicine.
• Existing strategies often require exogenous growth factors, increasing complexity and cost.

Purpose of the Study:

• To synthesize and characterize novel GelMA/CSMA composite microspheres (G/CMS) for enhanced angiogenesis.
• To investigate the role of microsphere size and surface charge in promoting cellular interactions and vascularization.
• To evaluate the efficacy of G/CMS in promoting neovascularization in vitro and in vivo.

Main Methods:

• Gelatin methacryloyl (GelMA) and chitosan methacryloyl (CSMA) were synthesized and copolymerized.
• Hydrogel microspheres were fabricated via emulsification, UV-induced cross-linking, and freeze-drying.
• In vitro assays assessed human umbilical vein endothelial cell (HUVEC) behavior and angiogenic gene expression.
• In vivo studies utilized subcutaneous implantation and hindlimb ischemia models to evaluate neovascularization.

Main Results:

• Fabricated size-tunable, porous G/CMS with tunable mechanical properties and positive surface charge.
• Optimized G/CMS (G/CMS-B) significantly enhanced HUVEC proliferation, migration, and tube formation in vitro.
• Upregulation of key angiogenic genes (VEGF, ANG, KDR) observed without exogenous growth factors.
• In vivo models demonstrated accelerated neovascularization and blood flow recovery with excellent biocompatibility and injectability.

Conclusions:

• The developed G/CMS platform effectively promotes angiogenesis by modulating physicochemical cues.
• This synergistic approach offers a promising, cost-effective strategy for regenerative medicine applications.
• The biomaterial's properties support tissue regeneration by enhancing vascularization and cellular interactions.