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The Effect Of RhBMP-2 On Cortical Strut Allografts Healing And Remodeling: An Experimental Study

Posted on:2007-03-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y XiongFull Text:PDF
GTID:2144360182487257Subject:Surgery
Abstract/Summary:PDF Full Text Request
BackgroundRevision total hip arthroplasty (THA) is often complicated by bone loss in the proximal femur, perforation, or periprosthetic fracture on the femoral side. Restoration of bone stock to either provide stability of stem or to provide bone stock for future revision procedures is a critical element of revision THA. In patients with bone tumor resection, high-energy injuries or infections, bone defects make great challenges to the surgeons too. In these cases, bone grafting is usually needed. Autograft bone harvest encounters problems with the added surgical time, limited supply and morbidity of the donor site. Bone substitutes such as calcium phosphate and calcium sulfate ceramics are solely osteoconductive matrices, and only have minimal tensile strength. Therefore, various types of allografts are used in most of the cases. Cortical strut allograft has the biomechanical advantage over morselized bone allografts. It can serve as immediate structuralsupport, when severe bone loss presents in the proximal femoral site, or periprosthetic fracture occurs. Cortical strut allografts were widely used in revision THA, limb-salvage surgeries in the treatment of bone tumors or traumatic bone defects, almost all of them could get union with the host bone. However it takes 7~9 months to complete the union to host bone with radiographic viewr, much longer than that through normal fracture healing. In addition, delayed union or nonunion occasionally does occur. Histological findings in a proximal femoral structural allograft at ten years following revision THA showed that the structural bone graft remodeled sparsely and ingrowth of new bone into the graft rarely exceeded 5 mm. The slow healing, remodeling, and occasionally delayed union or nonunion, greatly affect the patient rehabilitation and clinical results.Bone morphogenetic proteins (BMPs) are signaling molecules that belong to the transforming growth factors fl (TGF- £) superfamily. Since their discovery by Urist in 1965, great progress has been made about their identification, characterization and clinical applications. With the onset of molecular cloning techniques, they can be produced in large quantities as recombinant human BMPs (rhBMPs). They induce new bone formation by promoting osteoblastic differentiation of mesenchymal stem cells (MSCs). These proteins, especially such as rhBMP-2 and rhBMP-7, have been proved to be safe and efficaciousin accelerating fracture healing and repairing long-bone defects in various animal models. Clinically, rhBMP-2 has been shown, when applied to open tibia fractures, to reduce the frequency of secondary interventions, accelerate fracture and wound healing, and reduce the infection rate. RhBMP-2 also has been found to be effective in spinal fusion, and got results similar to or superior to autogenous cancellous bone grafts. One recent study demonstrated healing of an allograft osteotomy in animal models after augmentation with rhBMP-2. ObjectiveTo Investigate the effect of rhBMP-2 on healing of host-allograft junction and remodeling of onlay strut cortical allografts. Materials and methodsThe rabbits from a previous unrelated study were sacrificed as onlay strut allograft bone donors. Two and a half centimeters long femoral intercalary allografts were harvested from adult New Zealand rabbits aseptically. All soft tissue including the periosteum and surrounding muscles were stripped from the bone. These allografts were kept in a freezer at -80°C for at least 3 weeks.Thirty New Zealand rabbits aged 6~8 months were used for the experiment. Each rabbit underwent bilateral onlay allograft strut procedures to the proximal femur. An onlay graft was secured to the lateral femur with two wires. The left femur of each rabbit receivedrhBMP-2/gelatin device interposed between the allograft and host bone, no device was used on the other side. The rhBMP-2 device was manufactured and supplied sterile for implantation (Huadong Gene Technology Institute, Hangzhou, China). Animals were sacrificed at 4, 6, 8 weeks postoperative. The allograft strut healing and remodeling were analyzed by means of radiographic examination, non-decalcification sections, fluorescence tag, and computer-aided image analysis.All statistical analyses were performed with commercially available software (SAS Institute, Cary, NC, USA). The Wilcoxon signed-rank test was used to determine interobserver reliability between observer grades of the radiographic appearance. The effect of treatment and time postoperative on the radiographic scores and new bone formation ratio was determined using two-way analysis of variance (ANOVA). Kruskal-Wallis multiple comparisons were performed for each implant type at each period. We consider the results to be significant when/?<0.05. ResultsUnder gross appearance, on the left side, the junction of allograft-host was obscure, we could see new bone formation around the allograft bone, also some ectopic bone formation. On the control side, until at 8th week after surgery, we can see little new boneformation at the extremes of allograft.Statistical analysis revealed the effect of treatment (rhBMP-2) and time in situ both were statistically significant (p<0.05). The sides treated with rhBMP-2 had significantly higher radiographic scores than control sides at all periods. The scores of the experimental sides at 4 weeks postoperative are superior to that of the control sides at 8 weeks after surgery.New bone formation was more evident when examined by using fluorescent microscopy examination of tetracycline labeled technique. There was more labeled new bone at the allograft surface and in the Haversian canal and Volkman canal on the left sides than that on the right sides. The new bone formation ratio on the rhBMP-2 treated sides was great significant compared with control sides at all times, as was the effect of time. It showed more new bone formation surrounding and invading the allograft, indicating better allograft-host bone incorporation and allograft bone remodeling. ConclusionThe rhBMP-2 device improves and accelerates the course of cortical strut allograft healing and remodeling with host bone. It should be a substancial clinical advantage.
Keywords/Search Tags:Bone morphogenetic protein, Bone transplantation, Allograft
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