Substrate-independent polymer coating with stimuli-responsive dexamethasone release for on-demand fibrosis inhibition

Abstract

Tissue fibrosis caused by implantation of tissue engineering scaffolds is an urgent problem in clinical research. In this work, a substrate-independent coating with on-demand release of an antifibrotic drug has been fabricated to effectively address this issue. This coating was formed through a substrate-independent layer-by-layer (LBL) technique via a cationic polyelectrolyte (poly-diallyldimethylammonium, PDDA) and an anionic polyelectrolyte (poly-styrenesulfonate, PSS), where parts of PSS and PDDA were physically replaced by carboxyl functionalized polyethylene glycol grafted onto antifibrotic drug dexamethasone (DEX-PEG-COOH). Considering the easy generation of local inflammation after implantation, an ester bond was designed between PEG-COOH and DEX. Therefore, the overexpressed esterase under inflammatory conditions hydrolyzes the ester bond and thereby releases DEX from the film to inhibit fibrosis occurring in the tissue repair process. The in vivo capacity of this coating to restrain tissue fibrosis was investigated by a skin defect model using porous polycaprolactone (PCL) scaffolds as substrates. The experimental results showed that the fibrosis-related proteins (Col-I, TGF-β and fibronectin) and the infiltration of myofibroblasts (α-SMA) of skin tissues in the coated PCL scaffold group were significantly lower than those in the blank control group and pure PCL scaffold group. Moreover, the histological evaluations showed that the coating group could significantly decrease the deposition of collagen and meanwhile promote the partial regeneration of skin appendages. These results successfully demonstrate that the universal coating prepared with a simple protocol would be an effective strategy to address the fibrosis issues during tissue engineering.