Fibrin hydrogel incorporated with microspheres containing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) accelerated the healing of diabetic wounds in rats

Diabetic wounds are characterized by delayed healing due to impaired angiogenesis, chronic inflammation, and defective extracellular matrix formation. This study evaluated the therapeutic potential of a fibrin hydrogel incorporating microspheres loaded with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) (FHM) in promoting wound repair in a streptozotocin-induced diabetic rat model. Rats were randomly assigned to control, fibrin hydrogel alone (FH), or FHM groups, and wounds were assessed on days 7 and 14. Mechanical properties, stereological parameters, collagen deposition, and cytokine expression were analyzed. FHM treatment significantly improved tensile strength and stress-bearing capacity of the wound tissue compared to FH and control groups (P < 0.05). Stereological analysis revealed increased fibroblast proliferation and neovascularization, with a concomitant reduction in inflammatory cell infiltration in FHM-treated wounds at both time points (P < 0.05). Masson's trichrome staining demonstrated enhanced collagen deposition and maturation in the FHM group, indicating improved extracellular matrix remodeling. Molecular analysis showed elevated transforming growth factor beta (TGF-β) and VEGF expression, alongside decreased pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), suggesting a dual effect of promoting regeneration while attenuating inflammation. This multimodal approach holds promise as a potential therapeutic strategy for chronic diabetic wounds, offering both functional and structural benefits. Further long-term studies and clinical translation are warranted to evaluate safety and efficacy in human patients.