基于柠檬酸新型可降解骨生物材料修复大鼠骨缺损的实验研究

发布时间：2018-05-03 00:23

本文选题：柠檬酸 + 磷酸丝氨酸　；参考：《南方医科大学》2017年硕士论文

【摘要】：目的:探讨基于柠檬酸新型可降解骨生物材料对大鼠骨缺损修复的效果,评价材料生物相容性、降解性、骨传导能力、骨诱导能力等性能,为该材料的进一步研究和开发提供理论依据和参考资料,和为骨缺损修复材料的发展提供新的选择与思路。材料与方法:从仿生学角度出发,合成基于柠檬酸新型可降解骨生物材料(Biodegradable Photoluminescent Polymer-Phosphoserine-Hydroxylapatite,BPLP-PSer-HA),填充大鼠骨缺损(软骨内成骨来源股骨髁骨缺损模型、膜内成骨来源颅骨骨缺损模型),并与自体骨移植组(Autogenous Bone,AB)、空白对照组(CON 组)、Poly(1,8-Octanediol-co-Citric acid)-Hydroxylapatite(POC-HA)生物材料、Poly(lactide-co-glycolide)-Hydroxylapatite(PLGA-HA)生物材料对比对大鼠骨缺损修复效果。术后4周、8周、12周取材,从影像学和组织学两方面评价基于柠檬酸新型可降解骨生物材料(BPLP-PSer-HA)的生物相容性、降解性、骨传导能力、骨诱导能力等性能。结果:术后4周、8周、12周取材,Micro-CT扫描并重建及骨缺损关注区域(the volume of interest,VOI)新生骨骨矿化密度(bone mineral density,BMD)分析可见:两种骨缺损模型各个组随着时间推移,骨缺损内新生骨量逐渐增多,BMD逐渐增高;术后各个时间观察点骨缺损内修复速度均为AB组快于BPLP-PSer-HA材料组快于POC-HA材料组快于PLGA-HA材料组快于CON组。组织学染色显示,骨缺损内移植材料被纤维组织包绕,材料周围有血管长入,材料周围未见炎性细胞浸润,骨缺损边缘有新生骨组织形成,随着时间的推移,骨缺损内新生骨由边缘向内部生长,骨组织逐渐增多,在新生骨组织内含有大量以软骨形式存在。各个时间观察点比较可见,骨缺损内新生骨组织数量为AB组多于BPLP-PSer-HA材料组多于POC-HA材料组多于PLGA-HA材料组多于CON组。材料降解速率可见,随着时间推移,生物材料逐渐降解,PLGA-HA降解速度最快,快于成骨生成速度,在新生组织中纤维组织内形成大量的空泡;基于柠檬酸骨生物材料BPLP-PSer-HA、POC-HA材料降解速度相当,纤维组织内未见明显空泡形成,可见与成骨速度较一致。碱性磷酸酶(alkaline phosphatase,ALP)染色和骨钙素(osteocalcin,OCN)免疫组化结果提示:成骨细胞数量AB组大于BPLP-PSer-HA材料组大于POC-HA材料组大于PLGA-HA材料组大于CON 组。结论:基于柠檬酸新型可降解骨生物材料BPLP-PSer-HA材料可通过软骨内成骨方式修复大鼠骨缺损包括来源于软骨内成骨的股骨髁骨缺损和来源于膜内成骨的颅骨骨缺损,表现出良好的生物相容性、骨传导能力和合适的降解速度。与可降解骨生物复合材料POC-HA和PLGA-HA相比,BPLP-PSer-HA材料拥有更强的骨诱导能力,是一种良好的骨缺损填充材料。
[Abstract]:Objective: to investigate the effect of citric acid new biodegradable bone biomaterials on the repair of bone defects in rats, and to evaluate the biocompatibility, biodegradability, bone conduction ability and bone induction ability of the materials. It provides theoretical basis and reference materials for the further research and development of the material, and provides new options and ideas for the development of bone defect repair materials. Materials and methods: a new biodegradable bone biomaterial, Biodegradable Photoluminescent Polymer-Phosphoserine-Hydroxylapatiteine BPLP-PSer-HAN, was synthesized from the biomimetic point of view to fill the rat bone defect (model of femoral condylar defect derived from endochondral osteogenesis). The effect of polylactide-co-glycolide-Hydroxylapatitea (PLGA-HAA) biomaterials on repairing bone defects in rats was compared with autogenous bone graft group (Autogenous Bonea ABA) and control group (control group). The bone defects were repaired by Polylactide-co-glycolide-Hydroxylapatitel PLGA-HAA (Polylactide-co-glycolide-Hydroxylapatitetate PLGA-HAA) biomaterials in the control group (control group, n = 8 Octanediol-co-octanediol-co-Citacidine-Hydroxylapatite POC-HAA). The biocompatibility, biodegradability, bone conduction ability and bone induction ability of a new biodegradable bone biomaterial BPLP-PSer-HA based on citric acid were evaluated from imaging and histological aspects. Results: Micro-CT scanning and reconstruction of bone defect and bone mineral density of the new bone (volume of VOI) were obtained 4 weeks and 8 weeks and 12 weeks after operation. The amount of new bone in bone defect increased gradually and the repair rate of bone defect was faster in group AB than in group BPLP-PSer-HA than in group POC-HA and faster than that in group PLGA-HA at every time after operation. Histological staining showed that the graft material was wrapped in fibrous tissue around the material, no inflammatory cells infiltrated around the material, new bone tissue formed at the edge of the bone defect, and over time, The new bone in the defect grows from the edge to the inside, the bone tissue increases gradually, and there is a large amount of cartilage in the new bone tissue. The number of new bone tissue in bone defect was more in AB group than in BPLP-PSer-HA material group than in POC-HA material group than in PLGA-HA material group and CON group. The degradation rate of materials can be seen. With the passage of time, the degradation rate of PLGA-HA was the fastest, which was faster than that of osteogenesis, and a large number of vacuoles were formed in the fibrous tissue. The degradation rate of BPLP-PSer-HAPOC-HA was similar to that of BPLP-PSer-HAPOC-HA, and there was no obvious vacuole formation in fibrous tissue, which was consistent with the rate of osteogenesis. The results of alkaline phosphatase (ALP) staining and osteocalcin (OCN) immunohistochemistry showed that the number of osteoblasts in group AB was greater than that in group BPLP-PSer-HA and that in group POC-HA was greater than that in group PLGA-HA. Conclusion: BPLP-PSer-HA, a new biodegradable bone biomaterial based on citric acid, can be used to repair rat bone defect by endochondral osteogenesis, including femoral condylar bone defect derived from endochondral osteogenesis and skull bone defect derived from intramembranous osteogenesis. It shows good biocompatibility, bone conduction ability and suitable degradation rate. Compared with biodegradable bone biomaterials POC-HA and PLGA-HA, BPLP-PSer-HA has stronger bone induction ability and is a good filling material for bone defect.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R318.08;R68

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