Liquid-type nonthermal atmospheric plasma enhanced regenerative potential of silk–fibrin composite gel in radiation-induced wound failure

Abstract

Delayed wound healing in heavily irradiated areas is a serious clinical complication that makes widespread therapeutic use of radiation difficult. Efficient treatment strategies are urgently required for addressing radiation-induced wound failure. Herein, we applied liquid-type nonthermal atmospheric plasma (LTP) to a silk–fibrin (S[sbnd]F) composite gel to investigate whether controlled release of LTP from S[sbnd]F hydrogel not only induced favorable cellular events in an irradiated wound bed but also modulated the S[sbnd]F hydrogel microstructure itself, eventually facilitating the development of a regenerative microenvironment. Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed that LTP modulated the microstructures and chemical bindings of the S[sbnd]F gel. Improved cell viability, morphology, and extracellular matrix depositions by the LTP-treated S[sbnd]F hydrogel were identified with wound-healing assays and immunofluorescence staining. An irradiated random-pattern skin-flap animal model was established in six-week-old C57/BL6 mice. Full-thickness skin was flapped from the dorsum and S[sbnd]F hydrogel was placed underneath the raised skin flap. Postoperative histological analysis of the irradiated random-pattern skin-flap mice model suggested that LTP-treated S[sbnd]F hydrogel much improved wound regeneration and the inflammatory response compared to the S[sbnd]F hydrogel- and sham-treated groups. These results support that LTP-treated S[sbnd]F hydrogel significantly enhanced irradiated wound healing. Cellular and tissue reactions to released LTP from the S[sbnd]F hydrogel were favorable for the regenerative process of the wound; furthermore, mechanochemical properties of the S[sbnd]F gel were improved by LTP.