Examining the feasibility of a "top-down" approach to enhancing the keratinocyte-implant adhesion

The adhesion of human epidermal keratinocytes to the implant surface is one of the most critical steps during the patient's recovery from implantation of transcutaneous prosthesis. To improve the success rate of transcutaneous prosthetic implants, we explored a new "top-down" approach to promoting this dynamic adhering process through modulation of upstream cell signaling pathways. To examine the feasibility of this novel approach, we first established an in vitro platform that is capable of providing a non-invasive, real-time, quantitative characterization of the keratinocyte-implant interaction. This platform is based on the dissipation monitoring function of the quartz crystal microbalance with dissipation monitoring (QCM-D) in conjunction with the open-module setup of the QCM-D. We then employed this platform to assess the effects of various pathways-specific modulators on the adhering process of keratinocytes. We demonstrated that this "top-down" approach is as effective in enhancing the adhesion of keratinocytes as the conventional "bottom-up" approach that relies on modifying the substrate surface with the adhesion protein such as fibronectin. We envision that this new "top-down" approach combined with the QCM-D-based in vitro platform will help facilitate the future development of new therapies for enhancing osseointegration and promoting wound healing.