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.

Oral administration of sea cucumber (Stichopus japonicus) protein exerts wound healing effectsviathe PI3K/AKT/mTOR signaling pathway

“…COL I, FN 1 and Lam were produced by fibroblasts, as vital proteins in the extracellular matrix to regulate wound contraction. 38 OCL and ZO-1 also play an essential role in normal cell differentiation and connection, 39 their levels improved in the dSCP group. However, RT-PCR results showed that the content of related genes was the highest when the concentration of dSCP was 50 μg mL −1 , and decreased at 100 μg mL −1 (Fig.…”

Multi-layer-structured bioactive glass nanopowder for multistage-stimulated hemostasis and wound repair

“…Bioactive glass nanoparticles (BGN) are a unique class of biomaterials that have demonstrated the great potential in the field of skin tissue regeneration as they are able to accelerate the re-epithelization [ 13 ], enhance the angiogenesis [ 14 ] and modulate the inflammatory responses [ 15 ]. Additionally, BGN has also been reported to be biodegradable during the tissue repair.…”

The Roles of Junctional Adhesion Molecules (JAMs) in Cell Migration

“…JAM-A knockdown promotes keratinocyte proliferation and migration to improve the skin healing process in vivo , regulated by the signaling of FAK-mediated Erk1/2 activation ( Wang et al, 2018 ). Bioactive glass (BG) extracts a posttranscriptional regulation mechanism on the expression of JAM-A to assemble into TJs located along the edge of the cell membrane, involved in mediating the enhanced barrier function of the keratinocyte monolayers ( Tang et al, 2021 ).…”