Construction of chitosan-based asymmetric antioxidant and anti-inflammatory repair film for acceleration of wound healing

Oxidative stress damage caused by free radicals around the moist microenvironment of wound has been a clinical challenge in skin tissue healing. Here, a novel chitosan-based bioinspired asymmetric wound repair composite (BAWRC) film was designed by facilitated endogenous tissue engineering strategy through layer-by-layer self-assembly technology for accelerated wound healing. The asymmetric characteristics were skillfully reflected by two different functional layers: hydrophilic chitosan (CS)/silk fibroin (SF) repair layer, and a hydrophobic bacteriostatic tea tree oil (TTO) layer with a rough surface. Simultaneously, sodium ascorbate (SA)-entrapped poly (lactic-co-glycolic acid) (PLGA) microspheres are distributed homogeneously in the hydrophilic layer to induce antioxidant response for skin repair. The distinctive asymmetric structure of BAWRC film endows it with synergistic effects, i.e., protects against the risk of infection from the external environment and facilitates deep skin wound healing. Results show that the minimum inhibition and bactericidal concentration of the BAWRC film were 1.25 and 6.25 mg/mL, respectively, demonstrating good antibacterial properties. The content of biofilm formation was significantly reduced when the concentration of TTO exceeds 5 mg/mL, indicating TTO shows a positive effect on bacteriostasis. In addition, the DPPH rates of BAWRC film were up to 64.7 % after incubation for 12 h, which was ascribed to that the release of SA and TTO as a natural product could accelerate free radical scavenging. The BAWRC film exhibited excellent biocompatibility, and good antibacterial capacity, enhancing adhesion and proliferation of the NIH3T3 cell in vitro, further facilitating the healing of a rat full-thickness skin wounds model. Herein, this versatile asymmetric film possesses great potential for clinical management of wound healing and related soft tissue regeneration.