Development and characteristics of a synovial-like interface membrane around cemented tibial hemiarthroplasties in a novel rat model of aseptic prosthesis loosening.

OBJECTIVE Aseptic prosthesis loosening (APL) is related to the formation and aggressive growth of a synovial-like interface membrane (SLIM) between prosthesis and bone. However, investigation of the early phases of SLIM development in humans presents major difficulties. This study was undertaken to develop and characterize the usefulness of a novel animal model of APL that is based on an established model of defined exercise in a running wheel by Wistar rats that have been subjected to intracranial self-stimulation (ICSS). METHODS Cemented tibial hemiarthroplasties were implanted into the left knees of 7 male Wistar rats. After 2 weeks, exercise in a running wheel was started in all rats, with a running-load of 2 hours/day for 5 days/week. Six months postoperatively, the knee joints were removed, decalcified, and embedded in paraffin. Histologic evaluation on hematoxylin and eosin-stained sections was performed to investigate the development of a SLIM and the presence of cement debris particles. To characterize the SLIM on a molecular level and investigate growth-regulating factors, the expression of transforming growth factor beta (TGFbeta) and the anti-apoptotic molecule Bcl-2 was analyzed by immunohistochemistry. RESULTS Although the prostheses appeared mechanically stable after 6 months, the development of SLIM with areas of bone resorption was seen in all samples. Resembling human SLIM, these membranes consisted of loose fibrous tissue, with cement debris particles located particularly at sites originally attached to the prostheses. Immunohistochemistry studies revealed the expression of TGFbeta and Bcl-2 in all specimens. Interestingly, staining for TGFbeta and Bcl-2 was restricted to areas where the SLIM were attached to bone. In contrast, there was only negligible expression of both proteins at sites adjacent to the prostheses. CONCLUSION Our findings demonstrate that the ICSS Wistar rat model constitutes a feasible tool for studying early stages of APL, and specifically the effect of defined running exercise on SLIM formation. The results further suggest that both cellular proliferation, as stimulated by TGFbeta, and altered apoptosis contribute to early stages of SLIM formation. The expression patterns of TGFbeta and Bcl-2 indicate that the growth of the SLIM is initiated and promoted from the bone rather than from the prosthesis.