Reconstruction of the anterior cruciate ligament (ACL) with patellar tendon (PT) is a common procedure for the symptomatic ACL-deficient knee. Questions regarding graft incorporation, viability, and nutrition of the transplanted tissue are of concern. This relates to the graft's response to its new intrasynovial milieu and new physical forces. These factors were studied in a rabbit model of ACL reconstruction using PT and were evaluated with histological and biochemical parameters with respect to time. A histological and biochemical metamorphosis of the grafted PT occurred in this study. Autografts demonstrated a gradual assumption of the microscopic properties of normal ACL; by 30 weeks postoperatively, cell morphology was ligamentous in appearance. Normally, type III collagen is not observed in PT, however, a gradual increase in its concentration was seen in the grafts; by 30 weeks its concentration (10%) was the same as in normal ACL. Similarly, glycosaminoglycans content increased from its normally low level in PT to that found in native ACL. Collagen-reducible crosslink analysis demonstrated that grafted tissue changed from the normal PT pattern of low dihydroxylysinonorleucine (DHLNL) and high histidinohydroxymerodesmosine (HHMD) to the pattern seen in normal ACL (high DHLNL and low HHMD) by 30 weeks. These data suggest that when PT is placed in the anatomic and environmental milieu of the ACL, a "ligamentization" of the grafted tissue results; also the autograft initially depends on synovial fluid nutrition, as revascularization occurs after 6 weeks.
A rabbit model for anterior cruciate ligament (ACL) reconstruction using autogenous avascular patellar tendon (PT) was utilized to study the early events of graft incorporation. Histological observations demonstrated that autografts were centrally acellular with a peripheral rim of cells at 2 weeks, a central focal proliferation of cells at 3 weeks, and a cellular homogeneous distribution by 4-weeks postoperation. Graft necrosis followed by cellular proliferation suggested that a different population of cells other than the native PT fibroblasts may be inhabiting the graft. The extrinsic contribution of cells was studied by selective destruction of native PT cells with liquid nitrogen immersion prior to reconstruction of the ACL. The intrinsic contribution of cells was evaluated by sequestration of the PT graft in a semipermeable membrane before it was used to reconstruct the ACL. Histological analysis of tissue that was liquid N2 treated, used as an autograft, and then harvested 3-weeks postoperation revealed fibroblastic incorporation of the graft. In contrast, no cells were observed in semipermeable membrane sequestered autografts. These data suggest that autogenous ACL autografts of PT origin are repopulated by cells of external origin. In vitro control studies that were carried out in parallel demonstrated that PT fibroblasts could survive in tissue culture, but not in the synovial environment of the ACL. This suggests that fibroblasts from different sources have different, tissue-specific nutritional requirements.
An experimental biodegradable bone cement [poly(propylene fumarate)-methylmethacrylate] (PPF-MMA) has been compared in vivo with polymethylmethacrylate (PMMA) as a carrier agent for local release of antibiotics. This approach is potentially applicable to the treatment of chronic osteomyelitis where the clinical goal is to achieve sustained high concentrations of antibiotics locally in the infected bone. In our experiments, gentamicin- and vancomycin-impregnated cylindrical PMMA and PPF-MMA cement specimens were implanted subcutaneously in rats, and blood and wound fluid samples were obtained over a 2-week period. Antibiotic levels were determined using immunoassays, and microbiologic activity was confirmed with agar diffusion techniques. The biodegradable PPF-MMA cement achieved and maintained considerably higher wound antibiotic levels than did PMMA cement. Vancomycin levels for the PPF-MMA cement were greater than 20 times those for the PMMA cement at all sampling times from 24 h to 14 days. For both cements, the serum antibiotic concentrations remained safely below maximum levels recommended for parenteral therapy. Mechanical testing of the PPF-MMA cement showed that admixture of 3% by weight of antibiotic did not adversely affect material properties. We conclude that this experimental biodegradable bone cement (PPF-MMA) can be used as a carrier to achieve high sustained local levels and low serum levels of antibiotics. Because it is biodegradable and thus does not require a secondary procedure for removal, it has special potential for use in treatment of chronic osteomyelitis.
A biodegradable, particulate composite bone cement containing gentamicin and vancomycin was used for both treatment and prophylaxis of Staphylococcus aureus osteomyelitis in rats. Osteomyelitis was established by inoculating S. aureus into holes that were drilled in the proximal tibiae and were filled with polymethylmethacrylate (PMMA) cylinders. The cylinders were left in place for 3 weeks. The infections were serially evaluated by clinical and radiographic examination and by quantitative culture for colony forming units (CFUs) at the time the rats were killed. For treatment, cements containing antibiotic were implanted in animals that had established osteomyelitis and were left in place for an additional 3 weeks. Sites treated with biodegradable cement containing antibiotics exhibited significantly fewer CFUs in comparison with controls (p < 0.01). Sites treated prophylactically with the biodegradable cement developed no infections as evaluated by clinical or radiographic criteria or by quantitative culture. At this relatively early time, no significant difference in therapeutic effectiveness was found when either the biodegradable cement or PMMA was used as a carrier for antibiotics.
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