title: Epidermal and dermal integration into sphere-templated porous poly(2-hydroxyethyl methacrylate) implants in mice.
abstract: 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 (40 microm) and interconnecting throats (16 microm) were implanted in normal C57BL/6 mice for 7, 14, and 28 days. Poly(HEMA) was either untreated, keeping the surface nonadhesive 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, beta4 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 40 microm 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.
authors.affiliation: Department of Medicine (Dermatology), University of Washington, Seattle, Washington, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Fukano
authors.forename: M L
authors.initials: ML
authors.lastname: Usui
authors.forename: R A
authors.initials: RA
authors.lastname: Underwood
authors.forename: S
authors.initials: S
authors.lastname: Isenhath
authors.forename: A J
authors.initials: AJ
authors.lastname: Marshall
authors.forename: K D
authors.initials: KD
authors.lastname: Hauch
authors.forename: B D
authors.initials: BD
authors.lastname: Ratner
authors.forename: J E
authors.initials: JE
authors.lastname: Olerud
authors.forename: P
authors.initials: P
authors.lastname: Fleckman
mesh_terms: D000818:Animals; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D020007:Implants, Experimental; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D008689:Methacrylates / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016062:Porosity / Q000187:drug effects; D016707:Tissue Fixation
chemical_list: D008689:Methacrylates; C005044:hydroxyethyl methacrylate