"RhBMP-2 is currently FDA approved for clinical use in spinal fusions and management of open tibia fractures. RhBMP-7 has received a humanitarian device exemption (HDE) for treatment of recalcitrant tibial non-unions and established posterolateral spine pseudarthrosis      . Although BMPs are the most potent osteoinductive agents commercially available today, this therapy requires further optimization . "
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to compare the efficacy of adenoviral and lentiviral regional gene therapy in a rat critical sized femoral defect model. The healing rates and quality of bone repair of femoral defects treated with syngeneic rat bone marrow cells (RBMCs) transduced with either lentiviral vector (Group I) or adenoviral vector (Group II) expressing bone morphogenetic protein-2 (BMP-2) gene were assessed. RBMCs transduced with the adenoviral vectors produced more than 3 times greater (p<0.001) BMP-2 when compared to RBMCs transduced with lentiviral vectors in an in vitro evaluation. Serial bioluminescent imaging demonstrated short duration luciferase expression (less than 3 weeks) in defects treated with RBMCs co-transduced with two adenoviral vectors (Group IV; adenovirus expressing BMP-2 and luciferase [Ad-BMP-2+Ad-Luc]). In contrast, the luciferase signal was present for 8 weeks in defects treated with RBMCs co-transduced with two lentiviral vectors (Group III; lentivirus expressing BMP-2 and luciferase gene [LV-BMP-2+LV-Luc]). There were no significant differences with respect to the radiological healing rates (p=0.12) in defects treated with lentiviral versus adenoviral mediated BMP-2 gene transfer. Biomechanical testing of healed Group I femoral specimens demonstrated significantly higher energy to failure (p<0.05) when compared to Group II defects. Micro CT analysis revealed higher bone volume/tissue volume fraction (p=0.04) in Group I defects when compared to Group II defects. In conclusion, prolonged BMP-2 expression associated with lentiviral mediated gene transfer demonstrated a trend towards superior quality of bone repair when compared to adenoviral mediated transfer of BMP-2. These results suggest that the bone repair associated with regional gene therapy is influenced not just by the amount of protein expression but also by duration of protein production. This observation needs validation in a more biologically challenging environment where differences in healing rates and quality of bone repair are more likely to be significantly different.
Bone 05/2008; 42(5):921-31. DOI:10.1016/j.bone.2007.12.216 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated tibialis posterior tendon (TPT) transfers in patients with drop foot deformity.
Eight patients with drop foot deformity (2 females, 6 males; mean age 40 years; range 15 to 75 years) underwent TPT transfer to the dorsum of the foot. The deformity was on the left in three patients and on the right in five patients. Etiology was traumatic peroneal nerve injuries in six patients, and upper-level nerve injuries after hip and lumbar surgery in two patients. For clinical evaluation, the patients were questioned about the results of treatment, and the Stanmore evaluation scale was applied, which is recommended by Yeap et al. for TPT transfers. The mean follow-up period was 39 months (range 8 to 78 months).
According to the Stanmore scale, the results were excellent in three patients, good in two patients, fair in two patients, and poor in one patient. Subjectively, four patients defined their condition as excellent, three as good, and one as poor. One poor result was associated with polytrauma sequelae including a femoral fracture, posterior acetabular fracture-dislocation, and L3 compression fracture, accompanied by at least a two-level injury to the sciatic nerve. Of two patients with a fair result, one patient developed deep infection at the dorsum of the foot due to inadequate postoperative care and required removal of the suture anchor with partial bone debridement. The other patient had severe paraparesis associated with congenital spondylolisthesis, which aggravated following spinal fusion surgery.
We conclude that TPT transfer is a successful technique for the treatment of drop foot even in ambulatory patients with paraparesis. Addition of tibialis anterior tendon transfer may be useful in these patients.
[Show abstract][Hide abstract] ABSTRACT: The need for bone tissue engineering has increased as the world population ages. The objectives of this study were to (1) develop a novel human umbilical cord mesenchymal stem cell (hUCMSC)-encapsulating, fiber-reinforced injectable calcium phosphate cement (CPCF) scaffold, and (2) investigate the effects of osteogenic media delivery, preosteodifferentiation, and bone morphogenetic protein-2 (BMP-2) delivery on hUCMSC osteodifferentiation inside CPCF for the first time. CPCF was developed using calcium phosphate powders, chitosan, and absorbable fibers. Four types of hUCMSC-encapsulating constructs were fabricated: control media in alginate hydrogel microbeads in CPCF; osteogenic media in microbeads; preosteodifferentiation; and recombinant human BMP-2 (rhBMP-2) in microbeads. The hUCMSCs inside CPCF maintained good viability, successfully differentiated into the osteogenic lineage, and synthesized bone minerals. The preosteodifferentiation method yielded high gene expressions of alkaline phosphatase, osteocalcin, collagen, and osterix, as well as alkaline phosphatase protein synthesis. The mineralization for the preosteodifferentiation constructs exceeded those of the rhBMP-2 group at 1-7 days, and was slightly lower than the rhBMP-2 group at 21 days. Mineralization of the rhBMP-2 group was 12-fold that of the control constructs at 21 days. In conclusion, although the BMP-2 delivery promoted osteodifferentiation, the preosteodifferentiation method and the ostegenic media method with hUCMSCs in CPCF were also promising for bone regeneration. hUCMSCs may be an effective alternative to the gold-standard bone marrow MSCs, which require an invasive procedure to harvest. The novel injectable stem cell-CPCF construct may be useful in minimally invasive and other orthopedic surgeries.
Tissue Engineering Part A 04/2011; 17(7-8):969-79. DOI:10.1089/ten.TEA.2010.0521 · 4.64 Impact Factor
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