Tang Jiajun, Guo Jinshan, Li Zhen, Yang Cheng, Xie Denghui, Chen Jian, Li Shengfa, Li Shaolin, Kim Gloria B, Bai Xiaochun, Zhang Zhongmin, Yang Jian
Academy of Orthopedics, Guangdong Province, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, China ; Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
J Mater Chem B. 2015 Jul 21;3(27):5569-5576. doi: 10.1039/C5TB00607D.
It is well known that high rates of fusion failure and pseudoarthrosis development (5~35%) are concomitant in spinal fusion surgery, which was ascribed to the shortage of suitable materials for bone regeneration. Citrate was recently recognized to play an indispensable role in enhancing osteconductivity and osteoinductivity, and promoting bone formation. To address the material challenges in spinal fusion surgery, we have synthesized mechanically robust and fast degrading citrate-based polymers by incorporating N-methyldiethanolamine (MDEA) into clickable poly(1, 8-octanediol citrates) (POC-click), referred to as POC-M-click. The obtained POC-M-click were fabricated into POC-M-click-HA matchstick scaffolds by compositing with hydroxyapatite (HA) for interbody spinal fusion in a rabbit model. Spinal fusion was analyzed by radiography, manual palpation, biomechanical testing, and histological evaluation. At 4 and 8 weeks post surgery, POC-M-click-HA scaffolds presented optimal degradation rates that facilitated faster new bone formation and higher spinal fusion rates (11.2±3.7, 80±4.5 at week 4 and 8, respectively) than the poly(L-lactic acid)-HA (PLLA-HA) control group (9.3±2.4 and 71.1±4.4) (p<0.05). The POC-M-click-HA scaffold-fused vertebrates possessed a maximum load and stiffness of 880.8±14.5 N and 843.2±22.4 N/mm, respectively, which were also much higher than those of the PLLA-HA group (maximum: 712.0±37.5 N, stiffness: 622.5±28.4 N/mm, p<0.05). Overall, the results suggest that POC-M-click-HA scaffolds could potentially serve as promising bone grafts for spinal fusion applications.
众所周知，脊柱融合手术中融合失败和假关节形成的发生率很高（5%~35%），这归因于缺乏适合骨再生的材料。柠檬酸盐最近被认为在增强骨传导性和骨诱导性以及促进骨形成方面起着不可或缺的作用。为了解决脊柱融合手术中的材料挑战，我们通过将N-甲基二乙醇胺（MDEA）引入可点击的聚（1,8-辛二醇柠檬酸酯）（POC-click）中，合成了机械性能强且降解速度快的柠檬酸盐基聚合物，称为POC-M-click。通过与羟基磷灰石（HA）复合，将得到的POC-M-click制成POC-M-click-HA火柴棒状支架，用于兔模型的椎间融合。通过X线摄影、手动触诊、生物力学测试和组织学评估来分析脊柱融合情况。术后4周和8周，POC-M-click-HA支架呈现出最佳降解率，促进了更快的新骨形成，并且脊柱融合率（4周和8周时分别为11.2±3.7、80±4.5）高于聚（L-乳酸）-HA（PLLA-HA）对照组（9.3±2.4和71.1±4.4）（p<0.05）。POC-M-click-HA支架融合的脊椎动物的最大载荷和刚度分别为880.8±14.5 N和843.2±22.4 N/mm，也远高于PLLA-HA组（最大载荷：712.0±37.5 N，刚度：622.5±28.4 N/mm，p<0.05）。总体而言，结果表明POC-M-click-HA支架有可能作为脊柱融合应用中有前景的骨移植材料。
