Bioactive glass promotes the barrier functional behaviors of keratinocytes and improves the Re-epithelialization in wound healing in diabetic rats

Abstract

Upon skin injury, re-epithelialization must be triggered promptly to restore the integrity and barrier function of the epidermis. However, this process is often delayed or interrupted in chronic wounds like diabetic foot ulcers. Considering that BG particles can activate multiple genes in various cells, herein, we hypothesized that bioactive glass (BG) might be able to modulate the barrier functional behaviors of keratinocytes. By measuring the transepithelial electrical resistance (TEER) and the paracellular tracer flux, we found the 58S-BG extracts substantially enhanced the barrier function of keratinocyte monolayers. The BG extracts might exert such effects by promoting the keratinocyte differentiation and the formation of tight junctions, as evidenced by the increased expression of critical differentiation markers (K10 and involucrin) and TJ protein claudin-1, as well as the altered subcellular location of four major TJ proteins (claudin-1, occludin, JAM-A, and ZO-1). Besides, the cell scratch assay showed that BG extracts induced the collective migration of keratinocytes, though they did not accelerate the migration rate compared to the control. The in vivo study using a diabetic rat wound model demonstrated that the BG extracts accelerated the process of re-epithelialization, stimulated keratinocyte differentiation, and promoted the formation of tight junctions in the newly regenerated epidermis. Our findings revealed the crucial effects of BGs on keratinocytes and highlighted its potential application for chronic wound healing by restoring the barrier function of the wounded skin effectively.