MSCs复合载万古霉素支架修复兔桡骨感染性骨缺损的实验研究
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摘要
研究背景及目的:
各种外伤、战伤所引起的感染性骨缺损在临床上十分常见。单纯的植骨术很可能因感染未控制而失败,因此患者往往不能进行一期植骨,而须彻底清创,待感染因素消除、伤口愈合、血管重建后再进行二期植骨修复骨缺损。这种治疗方法既增加了患者的痛苦,也延长了治疗时间,增加了医疗费用。近年的研究表明,载抗生素缓释系统,如聚甲基丙烯酸甲酯或者可降解的缓释材料复合抗生素系统等,可以有效控制感染,但由于其无促进成骨作用,因此骨愈合延迟或骨不连的情况仍时有发生。如能制备既可以有效释放抗生素控制感染,又能促进成骨的载抗生素缓释材料,将可能为感染性骨缺损的治疗提供一有效途径及手段。现阶段,骨组织工程学被认为是骨缺损修复的最理想方法之一。脱钙骨基质(demineralized bone matrix,DBM)具有传导成骨及诱导成骨的特性;具有良好的组织相容性和生物可降解性,降解产物对细胞无毒、无刺激;具有良好的孔隙率,可通过其表面化学结构及内部的各种生长因子和粘附分子,直接对细胞发挥作用,促进细胞生长,因此被认为是理想的骨组织工程材料。I型胶原是骨组织细胞外基质的主要成分。研究发现,胶原修饰的支架材料,对种子细胞的早期粘附及随后的分化、增殖及成骨均有促进作用。同时胶原也可作为药物的缓释载体。有研究表明,各种类型抗生素中,万古霉素对细胞的毒性最低,且能有效杀灭革兰氏阳性菌,对临床上较为棘手的严重的耐药金黄色葡萄球菌和表皮葡萄球菌等感染性疾病亦有较好疗效。因此,制备载万古霉素的胶原DBM支架材料,可能能有效控制抗生素在局部的释放,发挥其良好的抗菌活性,同时又可作为良好的种子细胞粘附载体。与此同时,由于骨髓间充质干细胞(mesenchymal stem cells,MSCs)具有多向分化潜能及自我更新能力,易于取材及体外培养扩增,并可进行自体移植,而被研究者视为最佳的种子细胞。因此,本研究拟对体外培养的兔骨髓间充质干细胞进行成骨诱导,再将其与载万古霉素的胶原DBM支架材料复合,植入兔桡骨感染性骨缺损处,观察其抗感染与促进骨愈合的能力,为临床感染性骨缺损的治疗提供实验基础。
实验方法:
1.采用Percoll密度梯度离心与贴壁培养相结合的方法分离、纯化、培养原代兔MSCs,对获得的细胞进行成骨诱导培养,以碱性磷酸酶染色、茜素红染色、四环素荧光标记法鉴定;对其进行成脂肪诱导培养,以油红染色鉴定;对其进行成软骨诱导培养,以阿新蓝染色鉴定。
2.观察不同浓度万古霉素(0μg/ml、100μg/ml、200μg/ml、400μg/ml、700μg/ml、1000μg/ml)及缓释万古霉素对体外培养MSCs的增殖、成骨分化的影响:以MTT比色法测定细胞生长率;测定碱性磷酸酶的活性;以茜素红染色观察MSCs诱导成骨情况;以半定量RT-PCR法检测诱导成骨后,成骨基因cbfα-1、I型胶原在mRNA水平上的表达。
3.制备载万古霉素的胶原DBM支架材料,以扫描电镜观察其表面形态,以高效液相色谱法测定其体外万古霉素释放曲线,以体外抑菌实验检测其抑菌能力。
4.将兔MSCs成骨诱导后,与载万古霉素胶原DBM支架材料体外复合,检测MSCs与支架材料的生物相容性:以扫描电镜观察支架表面形态及细胞生长情况;对粘附于支架上的MSCs予以胰酶消化后进行细胞计数、MTT比色法测定细胞生长率,检测与支架复合的MSCs的数量及增殖情况;测定碱性磷酸酶活性,检测与支架复合后的MSCs的成骨能力;以染色体核型分析、平板克隆实验、裸鼠致瘤性实验检测MSCs的致瘤性。
5.建立兔桡骨感染性骨缺损模型,将兔MSCs与载万古霉素胶原DBM支架材料体外复合后,植入兔桡骨感染性骨缺损处,通过一般情况的观察、血清C反应蛋白及红细胞沉降率的测定、X线摄片、组织学切片、生物力学测试,检测该生物复合材料的抗感染及促进成骨能力。
结果:
1.成功分离、纯化、培养获得原代兔MSCs。对其成骨诱导后,碱性磷酸酶染色、钙结节茜素红染色、四环素荧光标记均呈阳性;对其成脂肪诱导后,油红染色呈阳性;对其成软骨诱导后,阿新蓝染色呈阳性。
2.不同浓度万古霉素(0μg/ml、100μg/ml、200μg/ml、400μg/ml、700μg/ml、1000μg/ml)及缓释万古霉素条件下,体外培养的MSCs在细胞生长率、碱性磷酸酶活性、诱导成骨后成骨基因cbfα-1及I型胶原mRNA的表达各方面,均无统计学差异。
3.成功制备载万古霉素胶原DBM支架材料,其具有良好的万古霉素缓释能力及抑菌能力,万古霉素释放时间可持续32天,体外抑菌可持续4周。
4.将兔MSCs与载万古霉素胶原DBM支架材料体外复合,扫描电镜下观察可见,载万古霉素胶原DBM支架材料上有大量MSCs爬行、生长、聚集。与普通DBM支架相比较,载万古霉素胶原DBM支架材料更有利于MSCs的粘附、爬行、聚集,其粘附的MSCs数量显著增多,并保持MSCs的增殖能力及成骨能力。与载万古霉素胶原DBM支架材料复合培养的MSCs,染色体核型正常、平板克隆实验阴性、裸鼠致瘤实验阴性。
5.与吸附胶原的DBM支架组相比较,载万古霉素PDLLA/β-TCP支架组、载万古霉素胶原DBM支架组、MSCs复合载万古霉素胶原DBM支架组,抗感染能力均较强,其血清C反应蛋白及红细胞沉降率的下降速度均显著增快。术后X线摄片及组织学切片结果提示:与吸附胶原的DBM支架组、载万古霉素PDLLA/β-TCP支架组相比较,载万古霉素胶原DBM支架组、MSCs复合载万古霉素胶原DBM支架组的促进成骨作用显著。MSCs复合载万古霉素胶原DBM支架组的促进成骨作用,较载万古霉素胶原DBM支架组显著,其生物力学测试的扭转强度亦显著增强,与未骨折的正常对照组之间比较,无统计学差异。
结论:
1.以Percoll密度梯度离心法与贴壁培养相结合的方法,可获得纯度及数量均较高的原代兔MSCs,可满足实验研究的需求。
2.不同浓度万古霉素(浓度≤1000μg/ml)及缓释万古霉素对MSCs的增殖及成骨分化能力无明显影响。
3.制备的载万古霉素胶原DBM支架材料具有良好的万古霉素缓释能力及体外抑菌能力,是理想的载抗生素缓释材料。
4. MSCs与载万古霉素胶原DBM支架材料,具有良好的生物相容性:与支架复合后的MSCs仍具有良好的增殖能力及成骨活性,未见致瘤性。
5. MSCs复合载万古霉素胶原DBM支架材料,能较好地修复兔感染性桡骨缺损模型,具有良好的抗感染和促进成骨能力。
Background and Objective:
Infected bone defects are common caused by trauma or war high-energy injured fracture. The treat strategy aims at elimination of infection as the first and major objective and bone union as the next objective because of infection. The inflammation is characterized by a predominant presence of leukocytes and macrophages, which contribute to the destruction of bone tissues.Vascular channels are compressed and obliterated by the inflammatory process. The destruction of vascular channels leaves a portion of dead and infected bone (sequestrum) that is detached from the adjoining healthy bone and surrounded by avascular soft tissue. Owing to the impaired vascularity, antibiotics may not be delivered adequately to the lesion by the intravenous route. The local delivery of antibiotics is an effective option for treating infection. The most common of these is the incorporation of antibiotics into bone cement (polymethylmethacrylate (PMMA)) or a biodegradable carrier as slow release system .These materals can eat many types of infections,but They can’t repair bone defects.
The best release system can not only control bone infection, but also repair bone defects.Bone tissue engineering technigue is the best selection to repair bone defects.Scafflds are the important element of tissue engineering.Antibiotic loaded scafflds can not only release local antibiotic but also be attached by seeding cells.In this experiment,MSCs were isolated and inducted from rabbits in vitro and seeded on the vancomycin loaded collagen DBM scafflods to control bone infection and repair bone defects. and provide a potential treatment procedure for infected bone defects.
Methods:
1.The original generation of MSCs were isolated from bone marrow of rabbits by density gradient centrifugation and adherent culture.Culture-expanded were idetified with osteogenic, chondrogenic and adipogenic differentiation.
2.MTT assay, alkaline phosphatase (ALP) activity and reverse transcription polymerase chain reaction (RT-PCR) were used to observe the influence of different concentrations of vancomycin (0μg/ml、100μg/ml、200μg/ml、400μg/ml、700μg/ml、1000μg/ml)and delayed release vancomycin on the proliferation and osteoinductive differentiation in vitro.
3.The vancomycin loaded collagen DBM scafflods were made and the morphology, release characteristics of vancomycin and bacteriostasis ability were observed.
4.Mesenchymal stem cells seeded on the vancomycin loaded scaffolds .The MSC/scaffold constructs were cultured in vitro and the biocompatibility was detected using MTT assay, alkaline phosphatase (ALP) activity and scanning electronic microscopy (SEM). The cellar oncogenicity of the MSCs on the the vancomycin loaded scaffolds was observed.
5.To investigate the in vivo anti-infection and osteogenesis of the MSCs/ vancomycin loaded scaffolds, the biomaterals were implanted in rabbit infected radii bone defect and studied by macroscopic , C-reactive protein (CRP), erythrocyte sedimentation rate(ESR), X-ray radiographs, the histologic images and biomechanics.
Results:
1.Four days of MSCs of original generation,the fibroblast-like cell colony was observed and MSCs have fulfilled the bottom of the monolayer cultural bottle in 9-12 days,while the passage cells having done in 4-7 days.After the osteogenic induction, most of cells were polygonal and clustered. ALP staining was strong positive. Calcareous infarct could be detected by tetracycline dying in cell clump and stained red by alizarin red. After the adipogenic induction,most of cells were stained positive by oil red. After the chondrogenic induction,most of cells were stained positive by alcian blue.
2.The results of MTT assay, alkaline phosphatase (ALP) activity and reverse transcription-polymerase chain reaction (RT-PCR) of osteogenic genes showed that different concentrations of vancomycin (0μg/ml、100μg/ml、200μg/ml、400μg/ml、700μg/ml、1000μg/ml)and delayed release vancomycin have no effect on MSCs proliferation and osteogenic differentiation
3.The release of vancomycin from the vancomycin loaded scaffolds was good . The release of vancomycin and bacteriostasis ability can be sustained for 32 days.
4.The morphology of MSCs attached onto the scaffolds was evaluated using SEM shows that cells have dramatically reproduced and aggregated with each other to form stratified cell layers, accompanying with filamentous fibers formed on the surface. Statistical analysis indicated significant difference in the cell number between MSCs seeded on the vancomycin loaded collagen DBM scaffolds and empty DBM scaffolds through MTT assay. the level of ALP activity increased substantially on he vancomycin loaded collagen DBM scaffolds. Statistical analysis indicated that there was significant difference between all groups (p<0.05).
5.The caryotype of MSCs that were seeded on the vancomycin loaded collagen DBM scaffolds and cultured on them for 10 days was nomal,the clone formation experiment showed negative and the tumorgenesis experiment of nude mouse showed also negative.
6.The MSCs/ vancomycin loaded scaffolds and vancomycin loaded scaffolds control infection and facilitate new bone formation. Moreover, the introduction of MSCs to vancomycin loaded dramatically enhanced the efficiency of new bone formation.The vancomycin PDLLA/β-TCP could control infection but could not repair bone defects.The empty collagen DBM scaffolds could not control infection.
Conclusions:
1.The MSCs of third generation obtained from dissociating red marrow by density gradient centrifugation and adherent culture have matched the MSCs features in aspects of appearance.The MSCs can successfully be inductived to osteoblast, chondrocyte and adipocyte.The MSCs of third generation have high purity and considerable quantity and are good seeding cells in bone tissue engineering.
2.Different concentrations of vancomycin (≤1000μg/ml)and delayed release vancomycin have no effect on MSCs proliferation and osteogenic differentiation .
3.The vancomycin loaded collagen DBM scaffolds have good ability of release of vancomycin and bacteriostasis .They are good local delivery system. the vancomycin loaded scaffolds are biocompatible and have no negative effects on the MSCs in vitro.The MSCs on the vancomycin loaded collagen DBM scaffolds can grow dramatically and keep osteogenesis.The MSCs have no tumorgenesis.
4. The MSCs/ vancomycin loaded scaffolds and vancomycin loaded scaffolds control infection and facilitate new bone formation. The vancomycin loaded scaffolds have the potential to be applied in orthopedic to treat infected bone defect.
各种外伤、战伤所引起的感染性骨缺损在临床上十分常见。单纯的植骨术很可能因感染未控制而失败,因此患者往往不能进行一期植骨,而须彻底清创,待感染因素消除、伤口愈合、血管重建后再进行二期植骨修复骨缺损。这种治疗方法既增加了患者的痛苦,也延长了治疗时间,增加了医疗费用。近年的研究表明,载抗生素缓释系统,如聚甲基丙烯酸甲酯或者可降解的缓释材料复合抗生素系统等,可以有效控制感染,但由于其无促进成骨作用,因此骨愈合延迟或骨不连的情况仍时有发生。如能制备既可以有效释放抗生素控制感染,又能促进成骨的载抗生素缓释材料,将可能为感染性骨缺损的治疗提供一有效途径及手段。现阶段,骨组织工程学被认为是骨缺损修复的最理想方法之一。脱钙骨基质(demineralized bone matrix,DBM)具有传导成骨及诱导成骨的特性;具有良好的组织相容性和生物可降解性,降解产物对细胞无毒、无刺激;具有良好的孔隙率,可通过其表面化学结构及内部的各种生长因子和粘附分子,直接对细胞发挥作用,促进细胞生长,因此被认为是理想的骨组织工程材料。I型胶原是骨组织细胞外基质的主要成分。研究发现,胶原修饰的支架材料,对种子细胞的早期粘附及随后的分化、增殖及成骨均有促进作用。同时胶原也可作为药物的缓释载体。有研究表明,各种类型抗生素中,万古霉素对细胞的毒性最低,且能有效杀灭革兰氏阳性菌,对临床上较为棘手的严重的耐药金黄色葡萄球菌和表皮葡萄球菌等感染性疾病亦有较好疗效。因此,制备载万古霉素的胶原DBM支架材料,可能能有效控制抗生素在局部的释放,发挥其良好的抗菌活性,同时又可作为良好的种子细胞粘附载体。与此同时,由于骨髓间充质干细胞(mesenchymal stem cells,MSCs)具有多向分化潜能及自我更新能力,易于取材及体外培养扩增,并可进行自体移植,而被研究者视为最佳的种子细胞。因此,本研究拟对体外培养的兔骨髓间充质干细胞进行成骨诱导,再将其与载万古霉素的胶原DBM支架材料复合,植入兔桡骨感染性骨缺损处,观察其抗感染与促进骨愈合的能力,为临床感染性骨缺损的治疗提供实验基础。
实验方法:
1.采用Percoll密度梯度离心与贴壁培养相结合的方法分离、纯化、培养原代兔MSCs,对获得的细胞进行成骨诱导培养,以碱性磷酸酶染色、茜素红染色、四环素荧光标记法鉴定;对其进行成脂肪诱导培养,以油红染色鉴定;对其进行成软骨诱导培养,以阿新蓝染色鉴定。
2.观察不同浓度万古霉素(0μg/ml、100μg/ml、200μg/ml、400μg/ml、700μg/ml、1000μg/ml)及缓释万古霉素对体外培养MSCs的增殖、成骨分化的影响:以MTT比色法测定细胞生长率;测定碱性磷酸酶的活性;以茜素红染色观察MSCs诱导成骨情况;以半定量RT-PCR法检测诱导成骨后,成骨基因cbfα-1、I型胶原在mRNA水平上的表达。
3.制备载万古霉素的胶原DBM支架材料,以扫描电镜观察其表面形态,以高效液相色谱法测定其体外万古霉素释放曲线,以体外抑菌实验检测其抑菌能力。
4.将兔MSCs成骨诱导后,与载万古霉素胶原DBM支架材料体外复合,检测MSCs与支架材料的生物相容性:以扫描电镜观察支架表面形态及细胞生长情况;对粘附于支架上的MSCs予以胰酶消化后进行细胞计数、MTT比色法测定细胞生长率,检测与支架复合的MSCs的数量及增殖情况;测定碱性磷酸酶活性,检测与支架复合后的MSCs的成骨能力;以染色体核型分析、平板克隆实验、裸鼠致瘤性实验检测MSCs的致瘤性。
5.建立兔桡骨感染性骨缺损模型,将兔MSCs与载万古霉素胶原DBM支架材料体外复合后,植入兔桡骨感染性骨缺损处,通过一般情况的观察、血清C反应蛋白及红细胞沉降率的测定、X线摄片、组织学切片、生物力学测试,检测该生物复合材料的抗感染及促进成骨能力。
结果:
1.成功分离、纯化、培养获得原代兔MSCs。对其成骨诱导后,碱性磷酸酶染色、钙结节茜素红染色、四环素荧光标记均呈阳性;对其成脂肪诱导后,油红染色呈阳性;对其成软骨诱导后,阿新蓝染色呈阳性。
2.不同浓度万古霉素(0μg/ml、100μg/ml、200μg/ml、400μg/ml、700μg/ml、1000μg/ml)及缓释万古霉素条件下,体外培养的MSCs在细胞生长率、碱性磷酸酶活性、诱导成骨后成骨基因cbfα-1及I型胶原mRNA的表达各方面,均无统计学差异。
3.成功制备载万古霉素胶原DBM支架材料,其具有良好的万古霉素缓释能力及抑菌能力,万古霉素释放时间可持续32天,体外抑菌可持续4周。
4.将兔MSCs与载万古霉素胶原DBM支架材料体外复合,扫描电镜下观察可见,载万古霉素胶原DBM支架材料上有大量MSCs爬行、生长、聚集。与普通DBM支架相比较,载万古霉素胶原DBM支架材料更有利于MSCs的粘附、爬行、聚集,其粘附的MSCs数量显著增多,并保持MSCs的增殖能力及成骨能力。与载万古霉素胶原DBM支架材料复合培养的MSCs,染色体核型正常、平板克隆实验阴性、裸鼠致瘤实验阴性。
5.与吸附胶原的DBM支架组相比较,载万古霉素PDLLA/β-TCP支架组、载万古霉素胶原DBM支架组、MSCs复合载万古霉素胶原DBM支架组,抗感染能力均较强,其血清C反应蛋白及红细胞沉降率的下降速度均显著增快。术后X线摄片及组织学切片结果提示:与吸附胶原的DBM支架组、载万古霉素PDLLA/β-TCP支架组相比较,载万古霉素胶原DBM支架组、MSCs复合载万古霉素胶原DBM支架组的促进成骨作用显著。MSCs复合载万古霉素胶原DBM支架组的促进成骨作用,较载万古霉素胶原DBM支架组显著,其生物力学测试的扭转强度亦显著增强,与未骨折的正常对照组之间比较,无统计学差异。
结论:
1.以Percoll密度梯度离心法与贴壁培养相结合的方法,可获得纯度及数量均较高的原代兔MSCs,可满足实验研究的需求。
2.不同浓度万古霉素(浓度≤1000μg/ml)及缓释万古霉素对MSCs的增殖及成骨分化能力无明显影响。
3.制备的载万古霉素胶原DBM支架材料具有良好的万古霉素缓释能力及体外抑菌能力,是理想的载抗生素缓释材料。
4. MSCs与载万古霉素胶原DBM支架材料,具有良好的生物相容性:与支架复合后的MSCs仍具有良好的增殖能力及成骨活性,未见致瘤性。
5. MSCs复合载万古霉素胶原DBM支架材料,能较好地修复兔感染性桡骨缺损模型,具有良好的抗感染和促进成骨能力。
Background and Objective:
Infected bone defects are common caused by trauma or war high-energy injured fracture. The treat strategy aims at elimination of infection as the first and major objective and bone union as the next objective because of infection. The inflammation is characterized by a predominant presence of leukocytes and macrophages, which contribute to the destruction of bone tissues.Vascular channels are compressed and obliterated by the inflammatory process. The destruction of vascular channels leaves a portion of dead and infected bone (sequestrum) that is detached from the adjoining healthy bone and surrounded by avascular soft tissue. Owing to the impaired vascularity, antibiotics may not be delivered adequately to the lesion by the intravenous route. The local delivery of antibiotics is an effective option for treating infection. The most common of these is the incorporation of antibiotics into bone cement (polymethylmethacrylate (PMMA)) or a biodegradable carrier as slow release system .These materals can eat many types of infections,but They can’t repair bone defects.
The best release system can not only control bone infection, but also repair bone defects.Bone tissue engineering technigue is the best selection to repair bone defects.Scafflds are the important element of tissue engineering.Antibiotic loaded scafflds can not only release local antibiotic but also be attached by seeding cells.In this experiment,MSCs were isolated and inducted from rabbits in vitro and seeded on the vancomycin loaded collagen DBM scafflods to control bone infection and repair bone defects. and provide a potential treatment procedure for infected bone defects.
Methods:
1.The original generation of MSCs were isolated from bone marrow of rabbits by density gradient centrifugation and adherent culture.Culture-expanded were idetified with osteogenic, chondrogenic and adipogenic differentiation.
2.MTT assay, alkaline phosphatase (ALP) activity and reverse transcription polymerase chain reaction (RT-PCR) were used to observe the influence of different concentrations of vancomycin (0μg/ml、100μg/ml、200μg/ml、400μg/ml、700μg/ml、1000μg/ml)and delayed release vancomycin on the proliferation and osteoinductive differentiation in vitro.
3.The vancomycin loaded collagen DBM scafflods were made and the morphology, release characteristics of vancomycin and bacteriostasis ability were observed.
4.Mesenchymal stem cells seeded on the vancomycin loaded scaffolds .The MSC/scaffold constructs were cultured in vitro and the biocompatibility was detected using MTT assay, alkaline phosphatase (ALP) activity and scanning electronic microscopy (SEM). The cellar oncogenicity of the MSCs on the the vancomycin loaded scaffolds was observed.
5.To investigate the in vivo anti-infection and osteogenesis of the MSCs/ vancomycin loaded scaffolds, the biomaterals were implanted in rabbit infected radii bone defect and studied by macroscopic , C-reactive protein (CRP), erythrocyte sedimentation rate(ESR), X-ray radiographs, the histologic images and biomechanics.
Results:
1.Four days of MSCs of original generation,the fibroblast-like cell colony was observed and MSCs have fulfilled the bottom of the monolayer cultural bottle in 9-12 days,while the passage cells having done in 4-7 days.After the osteogenic induction, most of cells were polygonal and clustered. ALP staining was strong positive. Calcareous infarct could be detected by tetracycline dying in cell clump and stained red by alizarin red. After the adipogenic induction,most of cells were stained positive by oil red. After the chondrogenic induction,most of cells were stained positive by alcian blue.
2.The results of MTT assay, alkaline phosphatase (ALP) activity and reverse transcription-polymerase chain reaction (RT-PCR) of osteogenic genes showed that different concentrations of vancomycin (0μg/ml、100μg/ml、200μg/ml、400μg/ml、700μg/ml、1000μg/ml)and delayed release vancomycin have no effect on MSCs proliferation and osteogenic differentiation
3.The release of vancomycin from the vancomycin loaded scaffolds was good . The release of vancomycin and bacteriostasis ability can be sustained for 32 days.
4.The morphology of MSCs attached onto the scaffolds was evaluated using SEM shows that cells have dramatically reproduced and aggregated with each other to form stratified cell layers, accompanying with filamentous fibers formed on the surface. Statistical analysis indicated significant difference in the cell number between MSCs seeded on the vancomycin loaded collagen DBM scaffolds and empty DBM scaffolds through MTT assay. the level of ALP activity increased substantially on he vancomycin loaded collagen DBM scaffolds. Statistical analysis indicated that there was significant difference between all groups (p<0.05).
5.The caryotype of MSCs that were seeded on the vancomycin loaded collagen DBM scaffolds and cultured on them for 10 days was nomal,the clone formation experiment showed negative and the tumorgenesis experiment of nude mouse showed also negative.
6.The MSCs/ vancomycin loaded scaffolds and vancomycin loaded scaffolds control infection and facilitate new bone formation. Moreover, the introduction of MSCs to vancomycin loaded dramatically enhanced the efficiency of new bone formation.The vancomycin PDLLA/β-TCP could control infection but could not repair bone defects.The empty collagen DBM scaffolds could not control infection.
Conclusions:
1.The MSCs of third generation obtained from dissociating red marrow by density gradient centrifugation and adherent culture have matched the MSCs features in aspects of appearance.The MSCs can successfully be inductived to osteoblast, chondrocyte and adipocyte.The MSCs of third generation have high purity and considerable quantity and are good seeding cells in bone tissue engineering.
2.Different concentrations of vancomycin (≤1000μg/ml)and delayed release vancomycin have no effect on MSCs proliferation and osteogenic differentiation .
3.The vancomycin loaded collagen DBM scaffolds have good ability of release of vancomycin and bacteriostasis .They are good local delivery system. the vancomycin loaded scaffolds are biocompatible and have no negative effects on the MSCs in vitro.The MSCs on the vancomycin loaded collagen DBM scaffolds can grow dramatically and keep osteogenesis.The MSCs have no tumorgenesis.
4. The MSCs/ vancomycin loaded scaffolds and vancomycin loaded scaffolds control infection and facilitate new bone formation. The vancomycin loaded scaffolds have the potential to be applied in orthopedic to treat infected bone defect.
引文
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