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Summary: As part of the acute inflammatory response, neutrophils accumulate in the central nervous system af ter injury. Recently, a soluble human recombinant com plement receptor (sCR1; BRL 55730; T Cell Sciences, Inc., Cambridge, MA, U.S.A.) has been developed that inhibits the activation of both the classical and the alter native pathways of complement. sCR 1 attenuates the ef· fects of the aCUte inl1ammatory response in several mod els of injury outside the central nervous system. The role of complement in traumatic brain injury, however, re mains undefined. We hypothesized that treatment with sCRI would attenuate neutrophil accumUlation in the brain after cerebral trauma. Using a randomized, blinded protocol, 18 anesthetized Sprague-Dawley rats were pre treated with sCRl or saline (control) at both 2 hand 2 min before trauma (weight drop) to the exposed right parietal cortex. A third dose of sCRI (or saline) was given 6 h

The posterior maxilla has traditionally been one of the most difficult areas to successfully place dental implants due to poor bone quality and close approximation to the maxillary sinus. Sinus augmentation procedures have become a viable means of assuring adequate bone for the placement of dental implants in this area. However, with the techniques currently employed, a considerable variation in the quality of bone attained with the sinus augmentation procedure exists. The purpose of this in vivo study was to evaluate the healing response and bone formation stimulated by 3 doses of recombinant human osteogenic protein-1 (rhOP-1), 0.25, 0.6, and 2.5 mg OP-1 per gram of collagen matrix; natural bone mineral; or collagen matrix alone (control) placed in the maxillary sinus of adult chimpanzees. Results were assessed using clinical, histologic, and radiographic techniques. Radiographic analysis of the computed tomography scans taken at 1 week, and 2.5, 4.5, and 6.5 months revealed a more rapid mineralization with the 2.5 mg OP-1/g collagen matrix and natural bone mineral treatment groups. The incremental bone mineral density (BMD) increase for these 2 treatments from 1 week to 2.5 months was over 2.5 times the increase found with the collagen matrix alone; these 2 treatments also had a higher BMD at the most superior slices evaluated when compared to the other 3 groups. Biopsy specimens were taken at 3.5, 5.5, and 7.5 months and for all 5 treatment groups bone formation was observed at all time points in the majority of the specimens. At 7.5 months the 2.5 and 0.6 mg OP-1/g collagen matrix treatment groups had an increase in the percent bone area when compared to the matrix alone control. In conclusion, these results demonstrate that sinus augmentation with natural bone mineral or 2.5 mg OP-1/g collagen matrix induce comparable radiographic and histologic evidence of bone formation and that both of these treatments performed superior to the control group of collagen matrix alone based upon all methods of evaluation.

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The aim of this pilot study was to examine bone graft incorporation in femurs impacted with allograft bone alone (control group) or with allograft containing the bone morphogenetic protein OP-I (BMP-7) (OP-1 group) in a sheep model of cemented hemiarthroplasty. Two sheep in each group were sacrificed at 6, 18 and 26 weeks. Successful bone graft incorporation was evident in both groups by six weeks but in the OP-I group, there had been more extensive resorption of the graft. There was one case of excessive stem subsidence in the OP-1 group at six weeks. By 18 weeks, there was remodelling and trdbeculation of the new bone in the OP-1 group, but this appeared less advanced in the control group. By 26 weeks, there was remodelling of bone in the graft bed. The results of this small study suggest that OP-1 promotes initial graft resorption, thus hastening bone graft incorporation and remodelling in femoral impaction grafting. The one case of stem subsidence may be associated with the early resorption seen in the OP-1 group and reinforces the need for further studies, examining dose response and using precise measures of stem movement, before this BMP is used in femoral impaction grafting at revision hip arthroplasty.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant's efficacy for bone regeneration. The biomaterial carriers were a 'putty' carrier of carboxymethylcellulose and bovinederived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to "ungrafted" negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP-and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP-and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.