Calcium silicate accelerates cutaneous wound healing with enhanced re-epithelialization through EGF/EGFR/ERK-mediated promotion of epidermal stem cell functions

Background:Human epidermal stem cells(hESCs)play an important role in re-epithelialization and thereby in facilitating wound healing,while an effective way to activate hESCs remains to be explored.Calcium silicate(CS)is a form of bioceramic that can alter cell behavior and promote tissue regeneration.Here,we have observed the effect of CS on hESCs and investigated its possible mechanism.Methods:Using a mouse full-thickness skin excision model,we explored the therapeutic effect of CS on wound healing and re-epithelialization.In vitro,hESCs were cultured with diluted CS ion extracts(CSIEs),and the proliferation,migration ability and stemness of hESCs were evaluated.The effects of CS on the epidermal growth factor(EGF),epidermal growth factor receptor(EGFR)and extracellular signal-related kinase(ERK)signaling pathway were also explored.Results:In vivo,CS accelerated wound healing and re-epithelialization.Immunohistochemistry demonstrated that CS upregulated cytokeratin 19 and integrinβ1 expression,indicating that CS improved hESCs stemness.In vitro studies confirmed that CS improved the biological function of hESCs.And the possible mechanism could be due to the activation of the EGF/EGFR/ERK signaling pathway.Conclusion:CS can promote re-epithelialization and improve the biological functions of hESCs via activating the EGF/EGFR/ERK signaling pathway.