Osteoarthritis is the most common joint disease and a major cause of disability. The knee is the large joint most affected. While chronological age is the single most important risk factor of osteoarthritis, the pathogenesis of knee osteoarthritis in the young patient is predominantly related to an unfavorable biomechanical environment at the joint. This results in mechanical demand that exceeds the ability of a joint to repair and maintain itself, predisposing the articular cartilage to premature degeneration. This review examines the available basic science, preclinical and clinical evidence regarding several such unfavorable biomechanical conditions about the knee: malalignment, loss of meniscal tissue, cartilage defects and joint instability or laxity.Level of evidence IV.
Non-invasive imaging can provide essential information for the optimization of new drug delivery-based bone regeneration strategies to repair damaged or impaired bone tissue. This study investigates the applicability of nuclear medicine and radiological techniques to monitor growth factor retention profiles and subsequent effects on bone formation. Recombinant human bone morphogenetic protein-2 (BMP-2, 6.5 μg/scaffold) was incorporated into a sustained release vehicle consisting of poly(lactic-co-glycolic acid) microspheres embedded in a poly(propylene fumarate) scaffold surrounded by a gelatin hydrogel and implanted subcutaneously and in 5-mm segmental femoral defects in 9 rats for a period of 56 days. To determine the pharmacokinetic profile, BMP-2 was radiolabeled with 125I and the local retention of 125I-BMP-2 was measured by single photon emission computed tomography (SPECT), scintillation probes and ex vivo scintillation analysis. Bone formation was monitored by micro-computed tomography (μCT). The scaffolds released BMP-2 in a sustained fashion over the 56-day implantation period. A good correlation between the SPECT and scintillation probe measurements was found and there were no significant differences between the non-invasive and ex-vivo counting method after 8 weeks of follow up. SPECT analysis of the total body and thyroid counts showed a limited accumulation of 125I within the body. Ectopic bone formation was induced in the scaffolds and the femur defects healed completely. In vivo μCT imaging detected the first signs of bone formation at days 14 and 28 for the orthotopic and ectopic implants, respectively, and provided a detailed profile of the bone formation rate. Overall, this study clearly demonstrates the benefit of applying non-invasive techniques in drug delivery-based bone regeneration strategies by providing detailed and reliable profiles of the growth factor retention and bone formation at different implantation sites in a limited number of animals.
Biodegradable local antibiotic delivery systems have gained interest for prophylaxis and treatment of musculoskeletal infections. We studied the biodegradable materials Osteo- Set, DBX and Collagraft for local delivery of vancomycin and gentamicin in vitro. We determined the antimicrobial activity of vancomycin and gentamicin after mixing with each biodegradable material and determined the release of each antimicrobial from each material in an intermittent flow chamber. Antimicrobial activity was expressed as percent of antimicrobial loaded into each sample that was detected; antimicrobial release was expressed as concentration (microg/mL) after timed intervals of chamber flow, peak concentration, area under the curve and percent antimicrobial recovered. Activity of vancomycin after mixing with Osteo- Set, DBX and Collagraft was > 73%. Activity of gentamicin after mixing with DBX was 100%; after mixing with OsteoSet and Collagraft it was reduced to < 61%. AUC0-48hrs of vancomycin was 469, 426 and 432 microg x hr/mL, and the AUC0-48hrs of gentamicin was 368, 306 and 301 microg x hr/mL after release from OsteoSet, DBX, and Collagraft, respectively. Recovered percentages of vancomycin were 39%, 11% and 25%, and recovered percentages of gentamicin were 39%, 9% and 23% after release from OsteoSet, DBX, and Collagraft, respectively. OsteoSet, DBX and Collagraft may be suitable for local delivery of vancomycin and gentamicin.
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