Harnessing the FXII-Fibrin-Fibroblast Cascade to Overcome the "Inert Hard Implant-Active Soft Tissue Integration Conflict".

Abstract

Inert hard implant materials, known for their minimal interaction with host tissues, are widely applied in biomedical areas. However, these "rigid, inert" devices usually require integration with surrounding "soft, active" tissues. Divergent clinical outcomes of soft tissue integration yielded by congeneric inert materials call for a reinterpretation of the "inertness", and warrant a fresh look at the mechanisms of inert implant-mediated host responses. Here, this work probes this "inert hard implant-active soft tissue integration conflict" by comparing four model materials with notable clinical differences in soft tissue integration. The findings reveal significant diversity in coagulation-related protein adsorption, with coagulation factor XII (FXII) emerging as a key mediator of fibrin network assembly. Enhanced FXII adsorption on inert implant surfaces correlates with denser fibrin formation and improved soft tissue integration-related cellular processes in human fibroblasts. Further molecular assays suggest that the integrin β1-PI3K-Akt pathway underpins these effects. This bridging of real-world materials and fundamental mechanisms may reshape the understanding of the "inert hard implant-active soft tissue" synergy and propose a novel approach to promote soft tissue integration around inert hard implants by modulating coagulation processes through tuning FXII adsorption on implant surfaces.