Synergistic effect of highly aligned bacterial cellulose/gelatin membranes and electrical stimulation on directional cell migration for accelerated wound healing

Directional cell migration plays a pivotal role in wound healing; however, traditional wound management mainly focuses on providing permissive environment, less focused on regulating directional cell migration to achieve an active wound healing. Ordered topography and electric field (EF) stimulation are known to modulate cellular activities and may facilitate wound healing. Herein, we developed a new wound care system that combines the aligned bacterial cellulose (BC)/gelatin membrane with EF stimulation to guide the cell migration and promote wound healing. The prepared BC/gelatin membranes possessed highly aligned fiber structure, robust mechanical property, high thermal stability, favorable light transmittance, foldability, and surface roughness, as well as excellent biocompatibility. Especially, the 40% stretched BC/gelatin membrane promoted the adhesion, orientation and migration of NIH3T3 cells in vitro. Application of this aligned BC/gelatin membrane in an in vivo full-thickness wound model resulted in a better and faster wound healing than application of commercial TegadermTM film. Importantly, both in vitro and in vivo data showed that combined with EF (150 mV/mm), the aligned BC/gelatin membrane synergistically directed the migration of NIH3T3 cells, and significantly improved the wound healing process by speeding-up wound closure, increasing granulation tissue thickness, collagen deposition, angiogenesis, and upregulating the gene expression of α-SMA, AKT and ERK. These findings suggest that the combination of 40% stretched BC/gelatin membrane with EF could be a promising therapeutic strategy to guide cell migration for improved wound healing.