A wide variety of hard tissue substitute materials for reconstruction have been designed for use in dental and orthopaedic procedures. Most of the literature provides information on the osteocompatibility of these materials, and not on soft tissue compatibility. The bone bonding strength of the materials is relatively high, but there seems to be a lack of bonding properties with soft tissue which results in the formation of fibrous encapsulation. This lack of soft tissue bonding can lead to implant failure. Therefore in order to study how artificial materials may remain in the body for long periods of time and remain functional, it is vital to understand the fibrous tissue encapsulation process. Ultrahigh molecular weight polyethylene coated with RGD, RGE, Poly-L-Lysine, or saline was implanted into Sprague Dawley rats either intraperitoneally or subcutaneously for 12 weeks. Aseptic surgical techniques were followed according to standard laboratory procedures. Blood was collected weekly for the first 8 weeks and at 12 weeks, and analyzed for lactate dehydrogenase activity to assess muscle wasting and compatibility. Lactate dehydrogenase activity was elevated at weeks one and two for groups implanted with materials, in comparison to control unoperated animals. From weeks 3-12, the LDH activity was similar in all groups indicating that there was no adverse response to the implanted material. The implants were harvested at the end of 12 weeks, and the fibrous capsule was screened histologically to determine thickness and cell types at the interface. The results clearly showed that the implants that were placed subcutaneously had a less extensive fibrous and vascular tissue formation, than those implanted intraperitoneally. The results also indicated that the location of the implant intraperitoneally, determined the extent of the fibrous tissue formation. The implanted materials coated with RGD and Poly-L-Lysine had thicker fibrous capsule formation than RGE coated implanted at both the subcutaneous and intraperitoneal sites. The results also suggest that the implant-interface contained fewer inflammatory cells when the implants were placed subcutaneously. The overall results indicate that more than surface charge or coating govern the formation of fibrous tissue in vivo.