Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis.

Polyethylene glycol (PEG) hydrogel microspheres of controlled sizes and narrow size distribution were fabricated via electrospraying. To facilitate the formation of microspheres through electrospraying, the gelation time of PEG hydrogels by Michael's addition reaction between acrylate and thiol were optimized. The effect of electrospraying parameters such as applied voltage, flow rate, needle gauge, and tip to collector distance (TTCD) on Taylor cone formation and microsphere size and distribution was determined. Applied voltage and TTCD had the strongest influence on Taylor cone formation and microsphere size and distribution. By careful design of process parameters a wide range of PEG hydrogel microspheres were obtained, namely 70-700 mm in diameter. The biodegradable PEG hydrogel microspheres developed in this study through a combination of mild gelation chemistry and electrospraying will be valuable in a variety of biological applications including drug and protein delivery, cell encapsulation, and biosensors.

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Background:Bisphosphonates limit resorption by inhibiting osteoclast formation and activation. They are removed during preparation of demineralized bone matrix (DBM) particles, but it is not known if osteogenesis and incorporation of mineralized bone allografts from patients treated with oral bisphosphonates are affected in vivo.Methods:Human block allografts from 3 bisphosphonate-treated donors and 3 age and sex-matched control donors who had not received bisphosphonates were obtained (Musculoskeletal Transplant Foundation); one-half from each donor was demineralized. In the first study, 3 × 2-mm mineralized and demineralized cylindrical grafts were implanted bilaterally in the femoral metaphysis of 56 rats. In the second study, samples from each group were pooled, prepared as particles, and implanted bilaterally in the femoral marrow canal of 24 rats. Osseointegration, defined as native bone in contact with allograft, was assessed at 10 weeks by micro-computed tomography (CT) and histomorphometry.Results:Micro-CT showed greater bone volume in sites treated with demineralized samples compared with the control mineralized and bisphosphonate-exposed mineralized samples. More new bone was generated along the cortical-endosteal interface compared with mineralized samples. Histology showed significantly less new bone in contact with the mineralized bisphosphonate-exposed allograft (10.4%) compared with mineralized samples that did not receive bisphosphonates (22.8%) and demineralized samples (31.7% and 42.8%). A gap was observed between native bone and allograft in the bisphosphonate-exposed mineralized samples (0.50 mm2). The gap area was significantly greater compared with mineralized samples that did not receive bisphosphonates (0.16 mm2) and demineralized samples (0.10 and 0.03 mm2).Conclusions:Mineralized allografts were osseointegrated, but not remodeled or replaced by living bone, preventing full regeneration of the bone defect. Prior treatment of the donor with bisphosphonates affected osteogenesis, preventing osteointegration and remodeling of the allograft into the regenerating bone.Clinical Relevance:Clinical use of mineralized allografts from patients who had received bisphosphonate therapy needs to be evaluated; in this animal model, such grafts were not integrated into the host bone or remodeled, and full regeneration of the bone defects was prevented.

ObjectivesDue to bone loss, endosseous implants often require addition of a bone graft to support adequate primary fixation, bone regeneration, and osseointegration. The aim of this study was to compare effectiveness of autogenic and allogenic bone grafts when used during simultaneous insertion of the implant.Materials and Methods4‐mm‐diameter rabbit diaphyseal bone autografts or allografts (n = 16/group) with a 3.2‐mm pre‐drilled hole in the center were placed into a 4 mm defect in the proximal femur of 3.5 kg male New Zealand White rabbits. Machined 3.2 × 10 mm grit‐blasted, acid‐etched titanium–aluminum–vanadium (Ti6Al4V) implants were placed. Control implants were placed into progressively drilled 3.2‐mm holes in the contralateral limbs. Post‐insertion day 70, samples were analyzed by micro‐CT and calcified histology, or by mechanical torque and push‐out testing followed by decalcified histology.ResultsBoth grafts were integrated with the native bone. Micro‐CT showed less bone volume (BV) and bone volume/total volume (BV/TV) in the allograft group, but histology showed no differences in BV or BV/TV between groups. Allograft lacked living cells, whereas autograft was cellularized. No difference was found in maximum removal torque between groups. Compressive loading at the graft‐to‐bone interface was significantly lower in allograft compared with autograft groups.ConclusionsThere was less bone in contact with the implant and significantly less maximum compressive load in the allograft group compared with autograft. The allograft remained acellular as demonstrated by empty lacunae. Taken together, block allograft implanted simultaneously with an implant produces a poorer quality bone compared with autograft.