Decorin mediated biomimetic PCL-gelatin nano-framework to impede scarring

Abstract

Scars occur as a result of fibrosis after tissue damage or surgery and reports suggest that excessive Transforming growth factor-β (TGF-β) activity during the process of wound healing leads to progressive fibrosis. Decorin is an extracellular matrix (ECM) protein which regulates collagen fibrillogenesis. However, targeted delivery and effective protein therapy remains a challenge owing to degradation byproteases. Hence, we aimed to deliver Decorin in a sustainable mode for the reduction of TGF-β levels and subsequent scar formation. Herein, we have fabricated PCL-Gelatin bio-mimetic scaffolds to optimize the bio-activity and provide localized delivery of recombinant Decorin. The degradation and drug release patterns reveals that this biomaterial is biodegradable and offers sustained release of the recombinant Decorin. Decorin loaded nanofiber displayed lower adhesion and proliferation rates in in-vitro conditions. Moreover, Decorin loaded scaffolds demonstrated morphological changes in cells, specifically targeting the myofibroblast. The expression of TGF-β was also scrutinized to understand the effect of Decorin loaded nanofibers. Besides, in the in-vitro fibrotic model, Decorin loaded nanofibers efficiently reduced the expression of ECM related proteins. Therefore, we report the sustained delivery of the recombinant Decorin from nanofiber dressing to potentially obstruct scar formation during the process of wound healing.

Keywords: Fibroblast; Hypertrophic scar; PCL-gelatin nanofiber; TGF-β; Wound healing.