Covalent modification of porous implants using extracellular matrix proteins to accelerate neovascularization

Abstract

Healing associated with many polymeric biomedical implants commonly involves the formation of an avascular fibrous capsule. The lack of either formation or persistence of blood vessels in formed fibrous capsules, as well as a lack of new blood vessels within porous polymeric implants, often results in poor performance of the implant. The current study evaluated the use of extracellular matrix protein modification of a commonly used biomedical implant material, expanded polytetrafluoroethylene (ePTFE), as a mechanism to increase the neovascularization both within these porous implants and in tissue that forms in the peri-implant area. Discs of ePTFE were covalently modified with different extracellular matrix proteins including collagen type IV, fibronectin, and laminin type I. Discs were implanted into the adipose tissue of adult rats, and following a 5-week implant phase, histologic analysis of peri-implant tissue angiogenesis and implant neovascularization was performed. Striking differences were observed in angiogenic and neovascularization responses to matrix-modified ePTFE when compared with control, untreated ePTFE. Fibronectin treatment resulted in an extensive inflammatory response but, relative to the degree of inflammation, limited evidence of tissue angiogenesis or polymer neovascularization. Collagen type IV treatment groups exhibited a significant increase in angiogenesis in the peri-implant tissue with minimal evidence of implant neovascularization. In contrast to all other implant modifications, laminin type 1-treated ePTFE samples stimulated an extensive peri-implant tissue angiogenic response and a coordinate neovascularization of the porous interstices of the biomaterial.