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.

Percutaneous medical devices remain susceptible to infection and failure. We hypothesize that healing of the skin into the percutaneous device will provide a seal preventing bacterial attachment, biofilm formation, and subsequent device failure. Porous poly(2-hydroxyethyl methacrylate) [poly(HEMA)] with sphere-templated pores (40μm) and interconnecting throats (16μm) were implanted in normal C57BL/6 mice for 7, 14 and 28 days. Poly(HEMA) was either untreated, keeping the surface non-adhesive for cells and proteins, or modified with carbonyldiimidazole (CDI) or CDI reacted with laminin 332 to enhance adhesion. No clinical signs of infection were observed. Epidermal and dermal response within the poly(HEMA) pores was evaluated using light and transmission electron microscopy. Cells (keratinocytes, fibroblasts, endothelial cells, inflammatory cells) and basement membrane proteins (laminin 332, β4 integrin, type VII collagen) could be demonstrated within the poly(HEMA) pores of all implants. Blood vessels and dermal collagen bundles were evident in all of the 14 and 28 day implants. Fibrous capsule formation and permigration were not observed. Sphere-templated polymers with 40μm pores demonstrate an ability to recapitulate key elements of both the dermal and the epidermal layers of skin. Our morphological findings indicate that the implant model can be used to study the effects of biomaterial pore size, pore interconnect (throat) size, and surface treatments on cutaneous biointegration. Further, this model may be used for bacterial challenge studies.

Percutaneous medical devices are integral in the management and treatment of disease. The space created between the skin and the device becomes a haven for bacterial invasion and biofilm formation and results in infection. We hypothesize that sealing this space via integration of the skin into the device will create a barrier against bacterial invasion. The purpose of this study was to develop an animal model in which the interaction between skin and biomaterials can be evaluated. Porous poly(2-hydroxyethyl methacrylate) [poly(HEMA)] rods were implanted for 7 days in the dorsal skin of C57 BL/6 mice. The porous poly(HEMA) rods were surface-modified with carbonyldiimidazole (CDI) or CDI plus laminin 5; unmodified rods served as control. Implant sites were sealed with 2-octyl cyanoacrylate; corn pads and adhesive dressings were tested for stabilization of implants. All rods remained intact for the duration of the study. There was histological evidence of both epidermal and dermal integration into all poly(HEMA) rods regardless of treatment. This in vivo model permits examination of the implant/skin interface and will be useful for future studies designed to facilitate skin cell attachment where percutaneous devices penetrate the skin.

Background-Keratinocyte migration is essential for wound healing and diabetic wound keratinocytes migrate poorly. Keratinocyte migration and anchorage appears to be mediated by laminin-332 (LM-332). Impaired diabetic wound healing may be due to defective LM-332 mediated keratinocyte migration.