Fabrication of a decellularized periosteum matrix-based alginate hydrogel containing collagen for enhanced diabetic...

The decellularized matrix retains essential biological macromolecules while eliminating cellular elements, making it promising for tissue repair owing to its biocompatibility and biological activity. The periosteum, which is abundant in collagen, vasculature, and cytokines, is well recognized for its role in bone regeneration; however, its potential in diabetic wounds (DWs) healing remains underexplored. In this study, a nicotinamide mononucleotide (NMN)-loaded periosteum-alginate-based (PSN) hydrogel was developed to facilitate DW healing through immunomodulation and neurovascular regulation. In vitro, the PSN hydrogel enhanced fibroblast proliferation, angiogenesis, and M2 macrophage polarization, and also reduced reactive oxygen species in peripheral nerve cells under hyperglycemic conditions. In vivo, the PSN hydrogel significantly accelerated wound healing in diabetic mice by promoting vascularization, exerting anti-inflammatory effects, and supporting nerve fibre regeneration. These findings highlight the therapeutic potential of decellularized periosteal matrices for DW treatment and provide new insights into matrix-based regenerative strategies.