Ability of Recombinant Human Bone Morphogenetic Protein 2 to Enhance Bone Healing in the Presence of Tobramycin: Evaluation in a Rat Segmental Defect Model

被引:22
作者
Glatt, Vaida [1 ,2 ]
Kwong, Francois N. [2 ,3 ]
Park, Kichul
Parry, Nicola [5 ]
Griffin, Damian [2 ]
Vrahas, Mark [4 ]
Evans, Christopher H. [3 ]
Harris, Mitchel [4 ]
机构
[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Sch Med, Boston, MA 02215 USA
[2] Univ Warwick, Dept Orthopaed Surg, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
[3] Harvard Univ, Sch Med, Ctr Mol Orthoped, Brigham & Womens Hosp, Boston, MA 02215 USA
[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners Orthoped Trauma Serv, Boston, MA USA
[5] Tufts Univ, Cummings Sch Vet Med, Sect Pathol, North Grafton, MA USA
关键词
tobramycin; BMP-2; Segmental defect; rat model; OPEN FRACTURES; ANTIBIOTIC-THERAPY; DELIVERY; FEMUR; BEADS; MANAGEMENT; INFECTION; TOXICITY; RHBMP-2;
D O I
10.1097/BOT.0b013e3181b01b2f
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
100224 [整形外科学];
摘要
Objective: To determine whether locally applied tobramycin influences the ability of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental defect in the rat femur. Methods: The influence of tobramycin on the osteogenic differentiation of mesenchymal stein cells was first evaluated in vitro. For the subsequent, in vivo experiments, a 5-mm segmental defect was created in the right femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator and four Kirschner wires. Rats were divided in four groups: empty control, tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 p,g)/absorbable collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at 8 weeks and the properties of the defect were compared with the intact contralateral femur. Bone formation in the defect region was assessed by dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing. Results: Tobramycin exerted a dose-dependent inhibition of alkaline phosphatase induction and calcium deposition by mesenchymal stein cells cultured under osteogenic conditions. The inhibition was reversed in the presence of 500 ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of rhBMP-2 to heal these defects and increased the bone area of the defects treated with rhBMP-2. Data obtained from all other parameters of healing, including dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing, were unaffected by tobramycin. Conclusions: Although our in vitro results suggested that tobramycin inhibits the osteogenic differentiation of mesenchymal stein cells, this could be overcome by rhBMP-2. Tobramycin did not impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats. Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with tobramycin. This study shows that locally applied tobramycin can be used in conjunction with rhBMP-2 to enhance bone formation at fracture sites.
引用
收藏
页码:693 / 701
页数:9
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