Multifunctional Metal Oxide-Doped Nanofluorophosphate Glass: A Bioactive Topical Formulation for Ischemic Wound Repair

Hypovascular or ischemic ulcer healing remains a significant challenge in regenerative medicine. Here, we report a novel topical formulation incorporating metal oxide-doped fluorophosphate (FP) glass to accelerate the healing of ischemic ulcers through enhanced angiogenesis and fibroblast migration. The bioactive FP glass nanoparticles (ZnFP, MgFP, and AgFP) were integrated with polymeric bases (PPF, 1,2-Diol, PEG, and PPG) to form biocompatible, nontoxic topicals. The formulations were systematically evaluated in vitro for cytotoxicity, migration assays, and angiogenesis potential using Chorioallantoic Membrane (CAM) assays and in vivo on full thickness cut and burn wound models. The optimized MgFP-PPG formulation exhibited a 9.8-fold increase in Epithelial Growth Factor (EGF) expression compared to that of controls, while AgFP-PPG enhanced Vascular Endothelial Growth Factor (VEGF) secretion by 4.2-fold. Scratch assays demonstrated considerably faster fibroblast migration, and CAM assays confirmed enhanced neovascularization with MgFP. In vivo, the MgFP-PPG formulation resulted in 72.5% wound contraction by day 7, compared to 61.3% with silver sulfadiazine and 45.8% in untreated wounds. Histopathological evaluation further revealed greater granulation tissue formation, increased Cluster of Differentiation 34 (CD34) expression, and enhanced VEGF signaling in burn wound models treated with MgFP-PPG and appreciably enhanced the wound healing by promoting cellular proliferation (Ki67). This study presents a promising approach for next-generation ischemic wound healing therapies.