title: Cutaneous and inflammatory response to long-term percutaneous implants of sphere-templated porous/solid poly(HEMA) and silicone in mice.
abstract: This study investigates mouse cutaneous responses to long-term percutaneously implanted rods surrounded by sphere-templated porous biomaterials engineered to mimic medical devices surrounded by a porous cuff. We hypothesized that keratinocytes would migrate through the pores and stop, permigrate, or marsupialize along the porous/solid interface. Porous/solid-core poly(2-hydroxyethyl methacrylate) [poly(HEMA)] and silicone rods were implanted in mice for 14 days, and for 1, 3, and 6 months. Implants with surrounding tissue were analyzed (immuno)histochemically by light microscopy. Poly(HEMA)/skin implants yielded better morphologic data than silicone implants. Keratinocytes at the poly(HEMA) interface migrated in two different directions. "Ventral" keratinocytes contiguous with the dermal-epidermal junction migrated into the outermost pores, forming an integrated collar surrounding the rods. "Dorsal" keratinocytes appearing to emanate from the differentiated epithelial layer, extended upward along and into the exterior portion of the rod, forming an integrated sheath. Leukocytes persisted in poly(HEMA) and silicone pores for the duration of the study. Vascular and collagen networks within the poly(HEMA) pores matured as a function of time up to 3-months implantation. Nerves were not observed within the pores. Poly(HEMA) underwent morphological changes by 6 months of implantation. Marsupialization, foreign body encapsulation, and infection were not observed in any implants.
authors.affiliation: Department of Medicine (Dermatology), University of Washington, Seattle, Washington, USA. fleck@u.washington.edu
authors.forename: Philip
authors.initials: P
authors.lastname: Fleckman
authors.forename: Marcia
authors.initials: M
authors.lastname: Usui
authors.forename: Ge
authors.initials: G
authors.lastname: Zhao
authors.forename: Robert
authors.initials: R
authors.lastname: Underwood
authors.forename: Max
authors.initials: M
authors.lastname: Maginness
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.forename: Christine
authors.initials: C
authors.lastname: Glaister
authors.forename: Buddy
authors.initials: B
authors.lastname: Ratner
authors.forename: John
authors.initials: J
authors.lastname: Olerud
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005260:Female; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011102:Polyhydroxyethyl Methacrylate / Q000009:adverse effects*; D016062:Porosity / Q000187:drug effects; D012828:Silicones / Q000009:adverse effects*; D012867:Skin / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012828:Silicones; D011102:Polyhydroxyethyl Methacrylate