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Biomedical subjects

Reggie C Hamdy

Publications and source records attributed to Reggie C Hamdy.

9 recordsLinked to original sources

Early injection of OP-1 during distraction osteogenesis accelerates new bone formation in rabbits.

Distraction osteogenesis (DO) is a surgical technique for generating new bone by applying controlled distraction of two bony segments post osteotomy. A limitation of the technique is the long time required for the new bone to consolidate. We investigated the effect of injecting osteogenic protein 1 (OP-1) at the beginning of distraction in a rabbit model of DO. Regenerate bone was evaluated using radiology, densitometry, micro-computed tomography (microCT) and histomorphometry. Immunohistochemsitry was used to evaluate changes in expression of various ligands, growth factors and receptors following OP-1 treatment. Compared to the control, a two-fold increase in bone volume was apparent for treated groups at 3 weeks post injection. An upregulation of almost all of the 41 genes examined was observed. Results suggested that applying OP-1 early during distraction can accelerate bone formation by the activation of numerous pathways. This study provides further insights on strategies to improve bone regeneration rate in DO.

Animals↗

Immunohistochemical localization of bone morphogenetic protein-signaling Smads during long-bone distraction osteogenesis.

In this study we investigated the expression of bone morphogenetic protein (BMP)-signaling Smads in distraction osteogenesis (DO). Osteotomy of the right tibia was performed in 14 skeletally mature white New Zealand male rabbits. Lengthening was started 1 week later at a rate of 0.5 mm/12 hr and was maintained for 3 weeks. Expression of Smad proteins 1, 4, 5, 6, 7, and 8 and Smad ubiquitin regulatory factors (Smurfs) 1 and 2 was evaluated in the distracted zone using immunohistochemistry. Expression of receptor-regulated Smads (R-Smads) 1, 5, and 8 showed a significant increase during the distraction phase, followed by a gradual decrease during the consolidation phase. Smad 4 showed significant expression during both distraction and the beginning of the consolidation phase. Smad 6 and Smad 7 were highly expressed during the consolidation phase. Staining for both Smurfs 1 and 2 was maximal at the end of the distraction period. Staining for all proteins was most intense in chondrocyte and fibroblast-like cells. Expression pattern of R-Smads correlated with our previously reported expression pattern of BMPs 2, 4, and 7 and their receptors. These results therefore suggest a role for the whole BMP signaling pathway including the Smad proteins in DO.

Animals↗

Effects of osteogenic protein-1 on distraction osteogenesis in rabbits.

In this study we tested the effect of locally applied osteogenic protein 1 (OP-1) on distraction osteogenesis in rabbits. Seven days after tibial osteotomy, distraction was started at a rate of 0.25 mm per 12 h for 3 weeks. At the end of the distraction period, OP-1 was injected at the site of osteotomy. Four different dosages were tested (0, 80, 800, or 2000 microg; eight rabbits per dose group). Rabbits were sacrificed 3 weeks later, and histologic, densitometric, and biomechanical parameters were assessed. No significant differences were found between groups for any parameter. To explain why this approach was only modestly successful, the expression of BMP receptor protein in the newly formed tissue was analyzed by immunohistochemistry. Strong expression of BMP receptor IA, IB, and II was found during the early distraction phase, but not during later stages of the process. Thus, it appears that the lack of receptor protein in the target tissue impairs the effect of OP-1 given at the end of the distraction period. Possibly, OP-1 could be more useful when applied early in the distraction phase.

Animals↗

Expression of bone morphogenetic proteins during mandibular distraction osteogenesis.

Distraction osteogenesis is a form of in vivo tissue engineering in which the gradual separation of cut bone edges results in the generation of new bone. In this study, the temporal and spatial expression of bone morphogenetic proteins (BMPs) 2, 4, and 7 was examined in a rabbit model of mandibular distraction osteogenesis. Fourteen skeletally mature male rabbits were studied. After osteotomy, a distractor was applied to one side of the mandible. After 1 week of latency, distraction was initiated at 0.25 mm every 12 hours for 3 weeks (distraction period), followed by a 3-week consolidation period. Two animals were killed each week after surgery. The generate bone was analyzed for the expression of BMP-2, -4, and -7 by using standard bone histological and immunohistochemical techniques. BMP-2 and -4 were highly expressed in osteoblastic cells during the distraction period and in chondrocytes during the consolidation period. BMP-7 demonstrated relatively minor expression in osteoblastic cells during the distraction period. All BMPs were strongly expressed in vascularized connective tissue during the distraction period. These data indicate that BMPs participate in the translation of mechanical stimuli into a biological response during mandibular distraction osteogenesis.

Animals↗

Serial bone densitometry during mandibular distraction osteogenesis.

The purpose of this study was to obtain serial measurements of bone mineral density (BMD) of the mandible during distraction osteogenesis. Fourteen skeletally mature male rabbits were subjected to unilateral mandibular osteodistraction at a defined rate. Two animals were sacrificed each week after surgery for 7 wk. The mandible and overlying soft tissue were resected and the BMD measured using dual-energy X-ray absorptiometry (DXA). Measurements obtained from the generate bone were compared to the contralateral (control) hemi-mandible. In the control hemi-mandible, BMD remained stable throughout the distraction protocol at 0.5 gm/cm2. In the distracted hemi-mandible, BMD sharply decreased to 0.35 gm/cm2 by the second week of distraction but steadily increased starting the third week of distraction. BMD surpassed control levels by wk 7. BMD measurements may provide a noninvasive assessment of bone mineralization and strength during distraction osteogenesis.

Absorptiometry, Photon↗

Effect of experimental parameters on the in vitro release kinetics of transforming growth factor beta1 from coral particles.

Coral bone graft substitutes have been supplemented in the past with growth factors to further enhance bone regeneration in defects. Little is known, however, on the dynamics of protein release from coral. Coral particles were studied for their ability to release transforming growth factor beta 1 (TGF-beta1) in vitro, under different adsorption conditions. Adsorption of TGF-beta1 (0.05 microg/mL) on coral particles (<80 microm or 300-450 microm) after 24 h of incubation was high, regardless of conditions. TGF-beta1 release kinetics in an artificial bone fluid followed a specific profile: an initial 1-h protein burst, followed by a decreasing release during the next 24 h at which time the release increased again to reach a constant rate until the end of the 2-week study. The protein release rate appeared mainly to depend upon the diffusion of TGF-beta1. TGF-beta1 release from coral particles was enhanced in the presence of bovine serum albumin (BSA) compared to the release in the presence of gelatin, and was dependent on the pH of adsorption. The highest total TGF-beta1 release was obtained when adsorption occurred with BSA at pH 7.4 (82 +/- 3%), while the lowest release was observed when adsorption was done in the presence of gelatin at pH 11 (38 +/- 1%). TGF-beta1 release was also found to vary with particle size, higher release being obtained with the smaller particles. These results suggest that coral particles could be used as a delivery system for growth factors, and that the release rate may be modulated through modification of the adsorption conditions and coral particle size.

Adsorption↗

Functional analysis of upper limb deformities in osteogenesis imperfecta.

The charts and radiographs of 159 children with osteogenesis imperfecta (OI) were retrospectively reviewed to measure the severity of upper limb deformities and to evaluate the functional outcome using the Pediatric Evaluation of Disability Inventory (PEDI). The patients were classified according to the Sillence classification modified by Glorieux: 51 type 1, 33 type 3, 54 type 4, and 21 5ype 5. Fifty-nine patients (37.1%) had deformities of their upper limbs. Children with type 3 OI had the highest incidence and the most severe deformities. The humerus was the most commonly involved bone, followed by the ulna and radius. Upper limb deformities were classified into four groups according to the severity of the maximum deformity angle. The mean self-care scores of PEDI were significantly low only in the group with severe deformities, but mobility scores were dramatically decreased in both the moderate and severe deformity groups. Therefore, upper limb deformities in children with OI do not represent only a cosmetic problem, but may also significantly impair functional activities of daily living.

Child↗

High prevalence of coxa vara in patients with severe osteogenesis imperfecta.

The purpose of this study was to determine the incidence and clinical presentation of coxa vara in 283 patients with osteogenesis imperfecta (OI). The charts and X-rays of 150 girls and 133 boys with OI were reviewed. The patients were classified according to the Sillence classification modified by Glorieux: 94 type I, 90 type IV, 67 type III, 18 type V, 10 type VI, and 4 type VII. The mean age was 9.4 years (range 0.3-23.3). Twenty-nine patients (10.2%) had coxa vara (23 left and 20 right). Fifty-five percent of them were type III, 24% type IV, 13.8% type VI, and 3.4% each of types V and VII. The incidence of coxa vara was 6% in type V, 8% in type IV, 24% in type III, 25% in type VII, and 40% in type VI (P < 0.001 for difference between types I, III, and IV). The mean neck-shaft angle was 99 degrees (range 80-110 degrees), the average head-shaft angle was 104 degrees (range 90-120 degrees), and the mean Hilgenreiner-epiphyseal angle was 68 degrees (range 40-90 degrees). Twenty-five patients (36 hips) had previous femoral rodding before diagnosis and seven hips (all type III) had no history of rodding. Abduction and internal rotation of the hip joints were restricted in all patients with this deformity. All children with coxa vara had a Trendelenburg gait. In conclusion, coxa vara in OI is not rare, especially in severe forms of the disease. Regular clinical and radiologic follow-up is indicated in children with previous femoral rodding and in severely affected children, particularly those with OI type III.

Adolescent↗