【作者】 王昕；

【导师】 赵杰；

【作者基本信息】 上海交通大学 ， 外科学（专业学位）， 2019， 硕士

【摘要】 目的:骨折术后骨不连一直是骨外科棘手的并发症,目前国际公认的治疗金标准是在坚强内固定的基础上进行植骨。但自体骨取骨造成的供骨区血肿、感染、慢性疼痛等并发症也不容忽视,因此寻求一种骨替代材料是当前的研究热点。人工骨虽然应用简便,但其往往缺乏骨生成作用。近年来研究表明骨髓间充质干细胞具备促进骨修复的作用,利用人工骨作为支架与干细胞结合构建组织工程生物材料可以起到优势互补作用。本研究通过分析利用自体骨移植与快速富集间充质干细胞的β-磷酸三钙支架植骨两种方式治疗骨不连患者的临床数据,验证团队自主研发的骨髓干细胞快速筛选-富集-复合系统对于骨修复的临床有效性。方法:选取我院2013年至2017年诊断为长骨骨不连且接受植骨手术的患者,试验组患者采用富集骨髓干细胞的β-磷酸三钙支架进行植骨,对照组采用自体骨移植。术后门诊随访评估两种植骨方式治疗后的骨愈合时间、影像学评分差异,同时评估骨髓干细胞快速筛选-富集-复合技术制备过程对于干细胞富集的相关参数,包括干细胞富集有效性、富集效率、细胞活力影响。结果:试验组及对照组各纳入30例及20例患者。骨髓干细胞快速筛选-富集-复合技术循环滤过过程可将骨髓中约82.0%的干细胞富集于多孔β-磷酸三钙材料表面,粘附的细胞高表达CD90(93.5%),CD105(89.4%),低表达CD34(0.1%),CD45(0.9%),且具备成骨、成脂、成软骨的三系诱导分化能力。滤过过程对细胞活力无显著机械损伤,平均每位患者植入(11444±6018)个干细胞。随访至术后9月,试验组及对照组各27例、18例患者获得临床愈合,临床愈合率均为90.0%,试验组临床愈合时间为(5.8±1.4)月,对照组临床愈合时间为(6.8±2.0)月,无统计学差异(P=0.064)。两组患者术后愈合影像评分均明显改善,术后9月评分无显著性差异。结论:骨髓干细胞快速筛选-富集-复合技术可有效富集骨髓中的间充质干细胞,且富集过程对细胞无明显机械损伤,制备的生物植骨材料具有良好的骨修复作用,其用于骨不连的治疗效果不劣于自体骨移植。更多还原

【Abstract】 Purpose Bone non-union after fracture,considering as a therapeutic challenge for orthopedics,the “golden standard” for treatment is autograft transplantation under stable internal fixation.However,adverse events related to autograft harvest,such as hematoma,infection,chronic pain,cannot be ignored.The application of artificial bone is rather convenient despite of its lack of osteogenesis.Bone mesenchymal stem cells(MSCs)has been proved to promoting bone regeneration by combine with certain scaffold.The study is designed to compare the promotion on bone regeneration of bone non-union between mesenchymal stem cells enriched-β-tricalcium phosphate(β-TCP)scaffold and autograft transplantation,confirming the clinical efficiency and security of bone marrow stem cell bone marrow stem cell Screen-Enrich-Combine Circulating System(SECCS)invented by our group.Methods: Patients suffered from lone bone non-union were enrolled in this retrospective casecontrolled study.Patients in the intervention group used β-tricalcium phosphate(β-TCP)scaffold seeding with mesenchymal stem cells manufactured by SECCS as bone graft.Patients in controlled group used autograft as bone graft.All patients accepted outclinical follow up.The evaluation indicators include bone union time and radiographic union score.In addition,the validity for stem cell enrichment,enrichment efficiency and cell viability during the procedure of SECCS were tested.Results: 30 non-union patients accepted SECCS therapy and 20 non-union patients accepted autograft transplantation(AGT)were enrolled.By SECCS therapy,about 82% MSCs were enriched from bone marrow without cell viability damaged and about(11444.0±6018)MSCs were transplanted per patient.Cells adhering to β-TCP particles were confirmed to possess ability for three-line differentiation and demonstrated highexpression of CD90(93.5%)and CD105(89.4%),and low-expression of CD34(0.1%)and CD45(0.9%).After 9 months’ out-clinical follow up,27 patients in SECCS group and 18 patients in AGT group acquired clinical union with the same clinical union rate of 90.0%,there was no significant difference for clinical union time between the two groups((5.8±1.4 vs 6.8±2.0 months,P=0.064).In addition,radiographic union scores of two group both improved after surgery and it demonstrated no statistic difference at 9th month post-operation.Conclusion: the SECCS could concentrate a large proportion of MSCs from bone marrow without damage of cell viability.Bone substitutes processed by SECCS demonstrated encouraging promotion of bone regeneration and showed satisfactory clinical curative effect for diaphyseal bone non-union,non-inferiority to autograft transplantation.更多还原