Reduced foreign body reaction to implanted biomaterials by surface treatment with oriented osteopontin

The foreign body reaction (FBR), which leads to the encapsulation of implanted biomaterials, has been implicated in the failure of many medical devices. The protein layer that is nonspecifically adsorbed onto the implant surface immediately after implantation is thought to dictate this reaction. It is hypothesized that biomaterial surfaces having specific proteins with precisely controlled orientations will decrease the FBR. Previously, we have reported that osteopontin (OPN) adsorbed on positively charged surfaces has a preferable orientation for in vitro cell adhesion and spreading as compared to negatively charged surfaces. It is expected that coating a layer of OPN in its preferred orientation on an implant surface will decrease the FBR. In this work, in vivo studies were performed to test this hypothesis. A positively charged polymer (p(HEMA-co-AEMA)) and a negatively charged polymer (p(HEMA-co-CEA)) coated with OPN were implanted subcutaneously in wild-type mice for 7 or 28 days. Uncoated polymers were used as control. For the 7-day implants, cells on OPN-coated p(HEMA-co-AEMA) spread more than cells on the other three materials. Following 28 days of implantation the implants were explanted and the capsule thickness and vascularity around the implants were characterized. Additionally, the macrophage and foreign body giant cells (FBGCs) around the implants were quantified. It was found in this study that the modification of the positively charged polymer surface with OPN in a controlled orientation led to a reduction in the foreign body reaction as determined by capsule thickness. Our finding provides valuable information for designing better biocompatible biomaterials with improved in vivo performance.