The effect of adherens junction components on keratinocyte adhesion in vitro: potential implications for sealing the skin-implant interface of intraosseous transcutaneous amputation prostheses.

Abstract

Amputation places a significant burden on healthcare systems worldwide as patients suffer life-long complications associated with the stump-socket interface. Skin penetrating, osseointegrated implants like intraosseous transcutaneous amputation prostheses, could overcome this, however, they rely on the formation and maintenance of an infection-free seal at the skin-implant interface. Epithelial cell migration around transcutaneous implants creates downgrowth, which leads to infection and implant failure. Epithelial cells form cell-cell attachments via adherens junctions and desmosomes that prevent cell migration via contact inhibition. If epithelial cells formed cell-cell attachments with an implant surface, it could facilitate stronger cell attachment and prevent downgrowth. In adherens junctions, E-cadherin is essential in homotypic cell attachment. In this study, we have demonstrated that cell-cell adherens junctions can be formed on substrates adsorbed with E-cadherin. We have assessed the effects of two E-cadherin peptides and determined an optimal concentration for increasing cell attachment via adherens junctions. We have demonstrated that adsorption of 15 μg/mL of the full extracellular domain of E-cadherin to titanium alloy significantly increases metabolic activity, cell area, and attachment of murine keratinocytes in vitro, with a fourfold increase in attachment via adherens junctions at 24, 48, and 72 h.