Natural polymeric and peptide-loaded composite wound dressings for scar prevention

Excessive or hypertrophic scarring after skin trauma can bring substantial psychological and socioeconomic burden. Achievement of attenuated scarring during wound repair remains a major clinical challenge. To limit pathological healing whilst attaining physiological restoration of skin integrity and function at wound sites, therapies should effectively reduce activity of scar-forming myofibroblasts without impeding normal granulation tissue formation by fibroblasts. Here, we developed an innovative wound dressing, prepared from genipin crosslinked hydrogel networks of carboxymethyl chitosan (CMCS), poly-γ-glutamic acid (γ-PGA) and anti-fibrotic polypeptide (AF38Pep). The composite wound dressing for healing and scar prevention (HSP) exhibited appropriate physicochemical, biocompatible, and wound dressing properties; while selectively inhibiting the proliferation, migration, and activity of pro-fibrotic cell phenotypes. RNA-Seq data revealed that wound dressings suppressed genes related to the focal adhesion pathway in heterograft keloid fibroblasts, and this was further attenuated by inclusion of AF38Pep. Furthermore, in vivo experiments in full-thickness dermal excision and hypertrophic scar models indicated that HSP promoted reduced-scar wound healing, as evidenced by attenuated inflammation; inhibition of fibroblast to myofibroblast differentiation; facilitation of distinct skin appendage regeneration; enhancement of vascularization; and regulation of favorable collagen deposition and distribution. Taken together, HSP wound dressings demonstrated multifunctional properties that supports their suitability as a candidate therapeutic option for anti-scarring skin repair.