title: Accelerated postero-lateral spinal fusion by collagen scaffolds modified with engineered collagen-binding human bone morphogenetic protein-2 in rats.
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.
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Xinglong
authors.initials: X
authors.lastname: Han
authors.affiliation: Orthopedic Institute of Soochow University, Suzhou, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Orthopedic Department, the Second Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ni
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Han
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
authors.affiliation: Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism*; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000601:surgery; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion / Q000379:methods*; D054457:Tissue Scaffolds; D055114:X-Ray Microtomography
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D003094:Collagen