Keratin-Based Temperature-Responsive Nanofiber Membranes with Tunable LCST for Controlled Drug Release and Wound Dressing Applications

Temperature-responsive nanofiber membranes have attracted increasing attention in the biomedical field, particularly in wound management and controlled drug delivery. Bio-based thermoresponsive polymers can integrate the advantages of natural materials with the temperature-responsive properties of poly(N-isopropylacrylamide) (PNIPAM). In this study, a keratin-based temperature-responsive polymer (KTRP) was constructed by grafting the rabbit hair keratin (RHK) with active thiol group (-SH) on the N-isopropylacrylamide (NIPAM) through a one-step thiol-Michael addition reaction. The resulting polymer has a good miscibility with soluble wool keratin (WK) in liquid solution. The mixed spinning solution of KTRP, WK, and poly(ethylene oxide) (PEO) showed good spinnability and was fabricated into temperature-responsive composite nanofiber membranes (KTRP/WK/PEO) by electrospinning. A 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/ N -hydroxysuccinimide (EDC/NHS)-mediated covalent crosslinking network was introduced to improve the water resistance and structural integrity of the nanofiber membranes. The effects of KTRP content and crosslinking time on the physicochemical properties, temperature-responsive behavior, and drug release performance of the membranes were systematically investigated. The results showed that the incorporation of KTRP effectively tuned the lower critical solution temperature (LCST) of the membranes within the range of 37.2-42.4°C and endowed them with reversible temperature-triggered shrinkage/expansion behavior. Appropriate crosslinking further improved the water resistance and thermal stability of the membranes without weakening their temperature-responsive performance. In addition, drug release experiments showed that the membranes exhibited accelerated release behavior above the LCST, confirming their temperature-responsive controlled-release capability. In vitro cytocompatibility evaluation further demonstrated that the composite nanofiber membranes were non-cytotoxic and supported the adhesion and proliferation of L929 cells. The research provides a simple method to synthesize the keratin-based temperature-sensitive polymer by one-step method. The prepared keratin-based temperature-responsive nanofiber membrane can serve as a promising biomaterial platform for smart wound dressings and temperature-responsive drug delivery.