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基于檸檬酸新型可降解骨生物材料修復(fù)大鼠骨缺損的實驗研究

發(fā)布時間:2018-05-03 00:23

  本文選題:檸檬酸 + 磷酸絲氨酸 ; 參考:《南方醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的:探討基于檸檬酸新型可降解骨生物材料對大鼠骨缺損修復(fù)的效果,評價材料生物相容性、降解性、骨傳導(dǎo)能力、骨誘導(dǎo)能力等性能,為該材料的進一步研究和開發(fā)提供理論依據(jù)和參考資料,和為骨缺損修復(fù)材料的發(fā)展提供新的選擇與思路。材料與方法:從仿生學(xué)角度出發(fā),合成基于檸檬酸新型可降解骨生物材料(Biodegradable Photoluminescent Polymer-Phosphoserine-Hydroxylapatite,BPLP-PSer-HA),填充大鼠骨缺損(軟骨內(nèi)成骨來源股骨髁骨缺損模型、膜內(nèi)成骨來源顱骨骨缺損模型),并與自體骨移植組(Autogenous Bone,AB)、空白對照組(CON 組)、Poly(1,8-Octanediol-co-Citric acid)-Hydroxylapatite(POC-HA)生物材料、Poly(lactide-co-glycolide)-Hydroxylapatite(PLGA-HA)生物材料對比對大鼠骨缺損修復(fù)效果。術(shù)后4周、8周、12周取材,從影像學(xué)和組織學(xué)兩方面評價基于檸檬酸新型可降解骨生物材料(BPLP-PSer-HA)的生物相容性、降解性、骨傳導(dǎo)能力、骨誘導(dǎo)能力等性能。結(jié)果:術(shù)后4周、8周、12周取材,Micro-CT掃描并重建及骨缺損關(guān)注區(qū)域(the volume of interest,VOI)新生骨骨礦化密度(bone mineral density,BMD)分析可見:兩種骨缺損模型各個組隨著時間推移,骨缺損內(nèi)新生骨量逐漸增多,BMD逐漸增高;術(shù)后各個時間觀察點骨缺損內(nèi)修復(fù)速度均為AB組快于BPLP-PSer-HA材料組快于POC-HA材料組快于PLGA-HA材料組快于CON組。組織學(xué)染色顯示,骨缺損內(nèi)移植材料被纖維組織包繞,材料周圍有血管長入,材料周圍未見炎性細胞浸潤,骨缺損邊緣有新生骨組織形成,隨著時間的推移,骨缺損內(nèi)新生骨由邊緣向內(nèi)部生長,骨組織逐漸增多,在新生骨組織內(nèi)含有大量以軟骨形式存在。各個時間觀察點比較可見,骨缺損內(nèi)新生骨組織數(shù)量為AB組多于BPLP-PSer-HA材料組多于POC-HA材料組多于PLGA-HA材料組多于CON組。材料降解速率可見,隨著時間推移,生物材料逐漸降解,PLGA-HA降解速度最快,快于成骨生成速度,在新生組織中纖維組織內(nèi)形成大量的空泡;基于檸檬酸骨生物材料BPLP-PSer-HA、POC-HA材料降解速度相當(dāng),纖維組織內(nèi)未見明顯空泡形成,可見與成骨速度較一致。堿性磷酸酶(alkaline phosphatase,ALP)染色和骨鈣素(osteocalcin,OCN)免疫組化結(jié)果提示:成骨細胞數(shù)量AB組大于BPLP-PSer-HA材料組大于POC-HA材料組大于PLGA-HA材料組大于CON 組。結(jié)論:基于檸檬酸新型可降解骨生物材料BPLP-PSer-HA材料可通過軟骨內(nèi)成骨方式修復(fù)大鼠骨缺損包括來源于軟骨內(nèi)成骨的股骨髁骨缺損和來源于膜內(nèi)成骨的顱骨骨缺損,表現(xiàn)出良好的生物相容性、骨傳導(dǎo)能力和合適的降解速度。與可降解骨生物復(fù)合材料POC-HA和PLGA-HA相比,BPLP-PSer-HA材料擁有更強的骨誘導(dǎo)能力,是一種良好的骨缺損填充材料。
[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.
【學(xué)位授予單位】:南方醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R318.08;R68

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