Percutaneous devices play an essential role in medicine; however, they are often associated with a significant risk of infection. One approach to circumvent infection would be to heal the wound around the devices by promoting skin cell attachment. We used two in vitro assay models to evaluate cutaneous response to poly(2-hydoxyethyl methacrylate) (poly(HEMA)). One approach was to use a cell adhesion assay to test the effects of surface modification of poly(HEMA), and the second used an organ culture system of newborn foreskin biopsies implanted with porous poly(HEMA) rods (20 microm pores) to evaluate the skin/poly(HEMA) interface. Surface modification of poly(HEMA) using 1,1'-carbonyldiimidazole (CDI) enhanced keratinocyte, fibroblast, and endothelial cell adhesion. Keratinocytes in the organ culture model not only remained functionally and structurally viable as observed by immunohistochemistry and electron microscopy, but migrated into the pores of CDI-modified poly(HEMA) rods. No biointegration was seen in the non-CDI-modified poly(HEMA). Laminin 5 immunostaining was seen along the poly(HEMA)/skin interface in a pattern resembling the junctional epithelium of the tooth, the unique natural interface between the skin and tooth that serves as a barrier to bacteria. In vitro systematic evaluation of biomaterials for use in animal implant studies is both cost effective and time efficient.