背景:制备一种可直接植入骨结核病灶内且在骨结核周围组织能够长期保持一定抗结核药物浓度,增强骨缺损修复的新型生物材料,成为骨结核临床研究的热点.目的:制备脂肪间充质干细胞与利福平缓释微球复合物,初步探讨其对兔脊柱结核模型的治疗作用.方法:合成利福平-壳聚糖-海藻酸钠缓释微球,将其与脂肪间充质干细胞复合培养,制作抗结核性骨组织工程复合体.取40只取新西兰大白兔,制作L6椎体结核模型,造模成功后随机分4组干预,对照组不进行任何干预;利福平组每天灌胃给予利福平;干细胞组在椎旁注射脂肪间充质干细胞,每天灌胃给予利福平;实验组在椎旁植入抗结核性骨组织工程复合体,每天灌胃给予利福平.给药8周后,通过X射线、CT初步观察病灶情况.结果与结论:对照组L5、L6椎体都有明显骨质破坏,形成炎性肉芽组织,椎间隙变窄,2只出现明显后凸畸形,5只兔腰大肌肿胀,腰大肌内可见低密度暗区.利福平组兔模型中5只兔L5和L6椎体有中度骨质破坏,2只兔腰大肌肿胀.干细胞组兔模型中2只兔L5和L6椎体有中度骨质破坏,3只兔L6椎体上部有轻度骨质破坏,3只兔腰大肌肿胀.实验组中4只兔L6椎体上部有轻度骨质破坏,L5、L6椎间隙无明显改变,无腰大肌肿胀发生.结果表明,脂肪间充质干细胞与利福平缓释微球复合物可抑制结核杆菌生长,减少椎体骨质破坏,对动物脊柱结核模型具有一定的治疗作用.%BACKGROUND: To prepare a novel biological material that can be implanted into the lesion of bone tuberculosis, keep sustained release of anti-tuberculosis drugs around bone tuberculosis tissues for a long time, and enhance the effect on bone repair has become a hot spot for clinical studies on bone tuberculosis.OBJECTIVE: To prepare the adipose-derived mesenchymal stem cells (ADMSCs)/sustained-release rifampin-loaded microsphere complex, and to preliminarily study its effects in a rabbit model of spinal tuberculosis.METHODS: Rifampin-chitosan-calcium alginate sustained-release microspheres were synthesized, and co-cultured with ADMSCs to prepare an anti-tuberculosis composite for bone tissue engineering. Forty New Zealand rabbits were used to make lumbar L6 tuberculosis models. Thereafter, rat models were randomly divided into four groups and given rifampin by gavage in rifampin group, ADMSCs by paravertebral injection+rifampin by gavage in stem cell group, rifampin by gavage+implantation of the anti-tuberculosis composite material in experimental group, and no treatment in control group.The duration time of rifampin administration was 8 weeks. The anti-tuberculosis effect of the composite material was evaluated by X-ray and CT scanning observation.RESULTS AND CONCLUSION: In the control group, obvious damage to lumbar vertebrae L5 and L6 was apparent; inflammatory granulation tissues formed; and the intervertebral space was narrowed. In addition, two rabbits in the control group showed obvious kyphotic deformity and five showed pasoas major swelling with low-density dark region in the psoas muscle. In the rifampin group, there were five rabbits with moderate damage of the lumbar vertebrae L5 and L6,and two rabbits with pasoas major swelling. In the stem cell group, there were two rabbits with moderate damage of the lumbar vertebrae L5 and L6, three rabbits with mild damage of the upper part of the lumbar vertebra L6, and three rabbits with pasoas major swelling. In the experimental group, only four rabbits suffered from mild damage of the upper part of the lumbar vertebra L6 but with no changes in the intervertebral space between the L5 and L6, and without pasoas major swelling. These results indicate that the composite material of ADMSCs combined with sustained-release rifampin-loaded microspheres can inhibit mycobacterial growth effectively, and reduce vertebral bone destruction,thereby giving some therapeutic actions for the animal models with spinal tuberculosis.
展开▼
