Engineering scalable production of pH-responsive self-assembling Azumapecten farreri-derived peptides for reduced-scarring wound repair.

Abstract

Food-derived self-assembling peptides offer multifunctional bioactivities for tissue repair, yet their biomedical use remains underexplored. Here, we report a scalable and controllable enzymatic enrichment process, enabling the production of pH-responsive self-assembling peptides (ANPs) from Azumapecten farreri via neutral protease hydrolysis. Critically, pH-responsiveness provides a tunable means to regulate the assembly pathway of ANPs by shifting protonation states, it tunes the balance between electrostatic and hydrophobic/π-π interactions, thereby modulating interfacial properties and nanostructure morphology across physiologically relevant pH milieus. This programmable assembly underpins ANPs' integrated bioactivities: in vitro, they exhibited antioxidant, pro-coagulant, and pro-proliferative effects. In a murine full-thickness wound model, both topical and oral ANPs accelerated closure, attenuated inflammatory infiltration, and promoted reduced scar residue with a collagen I/III balance consistent with regenerative remodelling; oral administration also largely maintained gut microbiota homeostasis. This study presents a novel strategy for the value-added exploitation of Azumapecten farreri resources and provides a clinically promising new material for reduced-scarring wound healing.