致密层骨软骨复合支架的制备及其修复关节骨软骨缺损
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摘要
背景:理想的骨软骨组织工程支架应巧妙地模拟人体正常关节骨软骨结构。目的:基于关节骨软骨的解剖结构、生理功能,制备致密层骨软骨复合支架,同时观察其修复兔关节骨软骨缺损的效果。方法:利用快速成型技术在三维立体包芯结构骨架表面喷涂乳酸-羟基乙酸共聚物/β-磷酸三钙有机溶液,形成0.5 mm的致密层;利用"溶解-粘连"工艺能将定向微管结构软骨支架与致密层相互连接,形成致密层骨软骨复合支架。取60只家兔,制备左膝关节软骨全层缺损,随机分3组,实验组植入致密层骨软骨复合支架,对照组植入定向微管结构软骨支架,空白对照组不植入任何材料,修复后12,24周进行缺损部位大体与组织学观察。结果与结论:1大体观察结果:对照组修复后12周存在明显缺损部位,未见明显修复痕迹;24周缺损面积减少,可见新生组织覆盖,但表面粗糙。实验组修复12周后缺损部位表面平整,质地较软,与周围组织边界不清;修复后24周,被透明软骨样组织覆盖,表面平整。空白对照组修复效果较差;2组织学观察结果:修复后12周,对照组缺损部位出现形态不规则的骨痂,但未形成骨小梁;实验组出现新生骨,软骨厚度与正常软骨接近,并且软骨下存在不规则骨小梁。修复后24周,对照组出现新生软骨,但厚度不均,高低不平,骨小梁结构不规则;实验组组织与正常组织无明显差异,软骨表面光滑;空白对照组修复效果较差;3结果表明:致密层骨软骨复合支架接近人体正常关节骨软骨结构,可促进关节软骨缺损的修复。
BACKGROUND: Ideal osteochondral tissue-engineered scaffolds should be able to mimic the normal structure of human articular cartilage. OBJECTIVE: To prepare a layered osteochondral composite scaffold based on the anatomical and physiological functions of osteochondral articular cartilage and to observe its repair effect on osteochondral defects in rabbits. METHODS: The poly(lactide-glycolide acid)/β-tricalcium phosphate organic solution was sprayed on the surface of cartilage scaffold using rapid prototyping technology. The layered osteochondral composite scaffold was formed by the "dissolving-adhesion" process. Sixty rabbits were enrolled, modeled into left knee articular cartilage defects, and then randomly divided into three groups. The layered osteochondral composite scaffold and cartilage scaffold were implanted into experimental and control groups, respectively. Those without any treatment served as controls. Gross and histological observations of the defect region were performed at 12 and 24 weeks after implantation. RESULTS AND CONCLUSION: Gross observation: At 12 weeks after implantation, the defects in the control group were obvious and not repaired at all; the 24-week defect area was decreased, covered by newly formed tissues, but with rough surface. In the experimental group, the defect surface was flat after 12 weeks of implantation, the texture was soft, and the boundary with the surrounding tissues was unclear; at 24 weeks, the defect was covered with transparent cartilaginous tissues and the surface was smooth. Histological observation: At 12 weeks after implantation, the irregular callus appeared in the control group, but the trabeculae were not formed; in the experimental group, the thickness of the new cartilage was similar with that of the normal cartilage and there was irregular trabecular bone under the cartilage. After 24 weeks of implantation, there were new tissues in the control group, but the thickness was irregular and uneven and the trabecular structure was irregular; while the cartilage surface was smooth and repaired well in the experimental group. In contrast, repair effect in the control group was poor as assessed by gross and histological observations. These results show that the layered composite scaffold holds a similar structure with human articular cartilage and can promote the repair of articular cartilage defects.
BACKGROUND: Ideal osteochondral tissue-engineered scaffolds should be able to mimic the normal structure of human articular cartilage. OBJECTIVE: To prepare a layered osteochondral composite scaffold based on the anatomical and physiological functions of osteochondral articular cartilage and to observe its repair effect on osteochondral defects in rabbits. METHODS: The poly(lactide-glycolide acid)/β-tricalcium phosphate organic solution was sprayed on the surface of cartilage scaffold using rapid prototyping technology. The layered osteochondral composite scaffold was formed by the "dissolving-adhesion" process. Sixty rabbits were enrolled, modeled into left knee articular cartilage defects, and then randomly divided into three groups. The layered osteochondral composite scaffold and cartilage scaffold were implanted into experimental and control groups, respectively. Those without any treatment served as controls. Gross and histological observations of the defect region were performed at 12 and 24 weeks after implantation. RESULTS AND CONCLUSION: Gross observation: At 12 weeks after implantation, the defects in the control group were obvious and not repaired at all; the 24-week defect area was decreased, covered by newly formed tissues, but with rough surface. In the experimental group, the defect surface was flat after 12 weeks of implantation, the texture was soft, and the boundary with the surrounding tissues was unclear; at 24 weeks, the defect was covered with transparent cartilaginous tissues and the surface was smooth. Histological observation: At 12 weeks after implantation, the irregular callus appeared in the control group, but the trabeculae were not formed; in the experimental group, the thickness of the new cartilage was similar with that of the normal cartilage and there was irregular trabecular bone under the cartilage. After 24 weeks of implantation, there were new tissues in the control group, but the thickness was irregular and uneven and the trabecular structure was irregular; while the cartilage surface was smooth and repaired well in the experimental group. In contrast, repair effect in the control group was poor as assessed by gross and histological observations. These results show that the layered composite scaffold holds a similar structure with human articular cartilage and can promote the repair of articular cartilage defects.
引文
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[13]高晓珺,解骏,肖涟波,等.骨碎补总黄酮对胶原诱导大鼠类风湿关节炎骨破坏治疗作用的实验研究[J].实用临床医药杂志,2013,17(5):13-17.
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[16]Cheng ZL,Hoi MW,Kelvin WKY,et al.The development,fabrication,and material characterization of polypropylene composites reinforced with carbon nanofiber and hydroxyapatite nanorod hybrid fillers.Int J Nanomed.2014;9:1299-1310.
[17]Kolmas J,Sobczak M,Oledzka E,et al.Synthesis,characterization and in vitro evaluation of new composite bisphosphonate delivery systems.Int J Mol Sci.2014;15(9):16831-16847.
[18]Wei B,Jin C,Xu Y,et al.Effect of bone marrow mesenchymal stem cells-derived extracellular matrix scaffold on chondrogenic differentiation of marrow clot after microfracture of bone marrow stimulation in vitro.Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi.2013;27(4):464-474.
[2]Hansen OM,Foldager CB,Christensen BB,et al.Increased chondrocyte seeding density has no positive effect on cartilage repair in an MPEG-PLGA scaffold.Knee Surg Sports Traumatol Arthrosc.2013;21(2):485-493.
[3]陈加荣,张余,黄华扬,等.磁力靶向传递SPIO标记的BMSC修复关节软骨缺损的研究进展[J].中国骨科临床与基础研究杂志,2014,6(2):118-122.
[4]刘拴,杨洪平,张卫国.关节镜下关节清理术治疗膝关节骨性关节炎的疗效分析[J].实用临床医学杂志,2014,18(1):58-60.
[5]Ito S,Sato M,Yamato M,et al.Repair of articular cartilage defect with layered chondrocyte sheets and cultured synovial cells.Biomaterials.2012;33(21):5278-5286.
[6]Yi L,Lin X.Tissue engineering technology for repair of articular cartilage injury.Chin J Tissue Eng Res.2013;17(41):7310-7316.
[7]张海峰,杜子婧,姜闻博,等.3D打印PLA-HA复合材料与骨髓基质细胞的相容性研究[J].组织工程与重建外科杂志,2015,11(6):349-353.
[8]Xue Z,Niu LY,An G,et al.Repairing rabbit’s radial bone defects using injectable nano-hydroxyapatite composite scaffold co-cultured with bone marrow mesenchymal stem cells.Chin J Tissue Eng Res.2015;3:378-383.
[9]王虔,马云胜,李德华.不同来源蚕丝蛋白修复骨软骨组织缺损的效果比较[J].中国组织工程研究,2015,19(52):8412-8417.
[10]Wray LS,Rnjak-Kovacina J,Mandal BB,et al.A silk-based scaffold platform with tunable architecture for engineering critically-sized tissue constructs.Biomaterials.2012;33:9214-9224.
[11]Stenhamre H,Nannmark U,Lindahl A,et al.Brittberg M Influence of pore size on the redifferentiation potential of human articular chondrocytes in poly(urethane urea)scaffolds.J Tissue Eng Regen Med.2011;5(7):578-588.
[12]Im GI,Ko JY,Lee JH.Chondrogenesis of adipose stem cells in a porous polymer scaffold:influence of the pore size.Cell Transplant.2012;21(11):2397-2405.
[13]高晓珺,解骏,肖涟波,等.骨碎补总黄酮对胶原诱导大鼠类风湿关节炎骨破坏治疗作用的实验研究[J].实用临床医药杂志,2013,17(5):13-17.
[14]Nishimoto S,Fukuda K,Kawai K,et al.Supplementation of bone marrow aspirate-derived platelet-rich plasma for treating radiation-induced ulcer after cardiac fluoroscopic procedures:A preliminary report.Indian J Plast Surg.2012;45(1):109-114.
[15]Viale-Bouroncle S,Gosau M,Morsczeck C.Collagen I induces the expression of alkaline phosphatase and osteopontin via inde-pendent activations of FAK and ERK signalling pathways.Arch Oral Biol.2014;59(12):1249-1255.
[16]Cheng ZL,Hoi MW,Kelvin WKY,et al.The development,fabrication,and material characterization of polypropylene composites reinforced with carbon nanofiber and hydroxyapatite nanorod hybrid fillers.Int J Nanomed.2014;9:1299-1310.
[17]Kolmas J,Sobczak M,Oledzka E,et al.Synthesis,characterization and in vitro evaluation of new composite bisphosphonate delivery systems.Int J Mol Sci.2014;15(9):16831-16847.
[18]Wei B,Jin C,Xu Y,et al.Effect of bone marrow mesenchymal stem cells-derived extracellular matrix scaffold on chondrogenic differentiation of marrow clot after microfracture of bone marrow stimulation in vitro.Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi.2013;27(4):464-474.