Drug and cell-eluting nanofibrous membranes for local anesthesia and skin wound healing.

The development of an ideal wound dressing that can both promote tissue regeneration and provide local anesthesia remains an unmet challenge. The existing approaches often employ separate strategies or products to heal the wound and manage pain, such as topical wound dressings and injectable agents. Electrospinning holds great potential to address this gap by enabling a single nanofibrous platform with multi-functionalities. In this work, poly (lactic-co-glycolic acid)/cellulose acetate (PLGA/CA) electrospun membranes loaded with bupivacaine and endometrial stem cells (EnSCs) were constructed as dual-functional systems for the sustained local anesthesia and wound healing. The scaffolds were prepared via electrospinning method and then characterized for morphology, mechanical properties, permeability, microbial barrier function, cytocompatibility, bupivacaine release profile, and EnSCs adhesion by scanning electron microscopy (SEM), tensile test, MTT assay, and fluorescence microscopy. The therapeutic efficacy of the scaffolds was evaluated in vivo in a rat excisional wound model over 14 days by wound closure rate, H&E and Masson's trichrome staining, histomorphometry, enzyme-linked immunosorbent assay (ELISA), and thermal response test. The obtained scaffolds exhibited homogeneous morphology, sustained bupivacaine release for 7 days, good mechanical properties, and excellent cytocompatibility. In addition, the EnSCs well adhered to the scaffolds with high viability. In vivo studies revealed that PLCELLBUPEnSCs significantly promoted wound closure, re-epithelialization, and collagen deposition, attenuated the secretion of pro-inflammatory cytokines, enhanced VEGF-A and TGF-β expression, and prolonged the duration of local anesthesia. In conclusion, this dual-functional scaffold demonstrates great potential as an advanced wound-care platform for tissue regeneration and local pain management.