Abstract
Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that plays a critical role in bone regeneration and repair. However, its distribution and side effects are major barriers to its success as therapeutic treatment. The improvement of therapy using collagen delivery matrices has been reported. To investigate a delivery system on postero-lateral spinal fusion, both engineered human BMP-2 with a collagen binding domain (CBD-BMP-2) and collagen scaffolds were developed and their combination was implanted into Sprague-Dawley (SD) rats to study Lumbar 4–5 (L4–L5) posterolateral spine fusion. We divided SD rats into three groups, the sham group (G1, n = 20), the collagen scaffold-treated group (G2, n = 20) and the BMP-2-loaded collagen scaffolds group (G3, n = 20). 16 weeks after surgery, the spines of the rats were evaluated by X-radiographs, high-resolution micro-computed tomography (micro-CT), manual palpation and hematoxylin and eosin (H&E) staining. The results showed that spine L4–L5 fusions occurred in G2(40%) and G3(100%) group, while results from the sham group were inconsistent. Moreover, G3 had better results than G2, including higher fusion efficiency (X score, G2 = 2.4±0.163, G3 = 3.0±0, p<0.05), higher bone mineral density (BMD, G2: 0.3337±0.0025g/cm3, G3: 0.4353±0.0234g/cm3. p<0.05) and more bone trabecular formation. The results demonstrated that with site-specific collagen binding domain, a dose of BMP-2 as low as 0.02mg CBD-BMP-2/cm3 collagen scaffold could enhance the posterolateral intertransverse process fusion in rats. It suggested that combination delivery could be an alternative in spine fusion with dramatically decreased side effects caused by high dose of BMP-2.
Highlights
Low back pain caused by instability of spine is a common disease as the population ages and life styles change
Collagen scaffolds were prepared in porosity As we expected, the collagen scaffolds were prepared from fresh bovine aponeurosis and characterized by a proper porosity (65%)
The biological activities of the collagen binding domain (CBD)-Bone morphogenetic protein-2 (BMP-2) and commercial BMP-2 were tested by the Alkaline phosphatase (ALP) activity assay using the MC-3T3-E1 cells
Summary
Low back pain caused by instability of spine is a common disease as the population ages and life styles change. Various factors, such as trauma, tumor, deformity, and degenerative disease, may play prominent roles in spine instability [1,2]. The limited source of autogenous iliac crest bone graft largely restricts its application to patients, especially the elderly and children [5]. Allogeneic bone is another possible source of the materials. Tissue engineering products have been considerated as the favorable alternative strategy
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