Proanthocyanidin nanoparticle-loaded collagen sponge for diabetic wound healing.

Diabetic wounds are persistently exposed to oxidative stress and impaired angiogenesis, resulting in delayed wound closure and compromised repair quality. Proanthocyanidins (PAC) exhibit favorable antioxidant activity; however, their insufficient aqueous dispersion stability and limited local bioavailability restrict their application in chronic wound repair. In this study, PEG-stabilized proanthocyanidin nanoparticles (PPN) were fabricated through a mPEG-SH mediated weakly alkaline oxidative assembly strategy and subsequently incorporated into commercial collagen sponges to prepare a composite dressing (CBS-PPN). Compared with PAC, PPN exhibited a more stable particle size distribution, improved cytocompatibility, and a more homogeneous distribution within the sponge. Further investigations demonstrated that CBS-PPN attenuated oxidative stress-induced damage and enhanced HUVEC tube formation in vitro. Transcriptomic analysis indicated that CBS-PPN regulated fibroblast repair-related processes, including cell adhesion, matrix remodeling, and stress injury responses, and may provide indirect support for a pro-angiogenic repair microenvironment. In a diabetic rat full-thickness skin defect model, CBS-PPN accelerated wound closure and promoted re-epithelialization, collagen deposition, and neovascularization. In summary, PEG-stabilized nanoparticle assembly improved the dispersion stability of PAC and its distribution within the collagen sponge, thereby enhancing their antioxidant and pro-repair effects. This study provides a new strategy for the development of natural polyphenol-based diabetic wound repair materials.