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Bone fracture healing impairment related to systemic diseases such as diabetes can be addressed by growth factor augmentation. We previously reported that growth factors such as fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) work synergistically to encourage osteogenesis in vitro. In this report, we investigated if BMP-2 and FGF-2 together can synergistically promote bone repair in a leporine model of diabetes mellitus, a condition that is known to be detrimental to union. We utilized two kinds of plasmid DNA encoding either BMP-2 or FGF-2 formulated into polyethylenimine (PEI) complexes. The fabricated nanoplexes were assessed for their size, charge, in vitro cytotoxicity, and capacity to transfect human bone marrow stromal cells (BMSCs). Using diaphyseal long bone radial defects in a diabetic rabbit model it was demonstrated that co-delivery of PEI-(pBMP-2+pFGF-2) embedded in collagen scaffolds resulted in a significant improvement in bone regeneration compared to PEI-pBMP-2 embedded in collagen scaffolds alone. This study demonstrated that scaffolds loaded with PEI-(pBMP-2+pFGF-2) could be an effective way of promoting bone regeneration in patients with diabetes.

SummaryObjectiveTranslation of promising treatments for post-traumatic osteoarthritis (PTOA) to patients with intra-articular fracture (IAF) has been limited by the lack of a realistic large animal model. To address this issue we developed a large animal model of IAF in the distal tibia of Yucatan minipigs and documented the natural progression of this injury.DesignTwenty-two fractures were treated using open reduction and internal fixation with either an anatomic reduction or an intentional 2-mm step-off. Pre-operatively, and 3 days, 1, 2, 4, 8, and 12 weeks post-operatively, animals were sedated for synovial fluid draws and radiographs. Limb loading was monitored at the same time points using a Tekscan Walkway. Animals were sacrificed at 12 weeks and the limbs were harvested for histological evaluation.ResultsAll animals achieved bony union by 12 weeks, facilitating nearly complete recovery of the initial 60% decrease in limb loading. TNFα, IL1β, IL6, and IL8 concentrations in the fractured limbs were elevated (P

back pain in 2000. Among individual drugs, ibuprofen and naproxen accounted for most of the prescriptions for traditional NSAIDs (60%), whereas two-thirds of the prescriptions for muscle relaxants were attributable to cyclobenzaprine, carisoprodol and methocarbamol. Prescription of COX-2 inhibitors or muscle relaxants demonstrated wide variations across different regions. Several individual characteristics including age, race and educational level were associated with the prescription of some of the medications. CONCLUSIONS: Neither traditional NSAIDs, nor COX-2 inhibitors, nor muscle relaxants dominated prescriptions for back pain. However, a small number of individual drugs were attributable to most of the prescriptions for traditional NSAIDs or muscle relaxants. The prescription of some of the medications demonstrated wide variations across different regions or different racial and educational groups. More studies are needed to understand why the variations occurred and how to standardize the prescriptions. Head-to-head comparisons of the relative costs and effectiveness among different categories of the medications, especially those drugs that have been most widely prescribed should also be warranted. DISCLOSURES: No disclosures. CONFLICT OF INTEREST: No Conflicts.