Tissue engineering of human cartilage and osteochondral composites using recirculation bioreactors

Tissue engineering of human cartilage and osteochondral composites using recirculation bioreactors
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DOI:
10.1016/j.biomaterials.2005.04.062
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发表时间:
2005-12-01
期刊:
影响因子:
14
通讯作者:
Doran, PM
Doran, PM
中科院分区:
工程技术1区
文献类型:
--
作者:
Mahmoudifar, N;Doran, PM

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从人胎儿骺软骨中分离软骨细胞,动态接种到聚乙醇酸(PGA)支架上,并在循环柱生物反应器中培养,以产生组织工程软骨。研究了几种有可能提供内源性生长因子和其他有利于从头软骨合成的条件的培养技术。骨软骨细胞复合结构的产生是通过将胎儿软骨细胞或胎儿成骨细胞接种到单独的PGA支架上,然后在生物反应器培养之前将支架固定在一起。这种类型的共培养系统提供了组织工程化软骨和发育中的组织工程化骨之间的直接接触,并产生了软骨质量的显着改善。在软骨部分的复合材料中,糖胺聚糖(GAG)和总胶原的浓度分别增加了55%和2.5倍,与对照软骨培养物相比,而11型胶原的水平与对照组相似。从生物反应器中收获骨软骨复合物作为软骨和骨组织之间具有良好整合的单个单元。只有软骨层含有GAG,而只有骨层被矿化。在其他实验中,组织工程化软骨与离体软骨或离体骨片的共培养相对于对照培养物没有改善软骨的质量。在培养液中加入10(-6)m双醋瑞因对工程化软骨的性质也没有影响。这项工作证明了产生软骨组织与发育中的骨骼接触的有益效果。它还证明了使用再循环柱生物反应器生产用于临床应用的复合骨软骨构建物的可行性。(c)2005爱思唯尔有限公司保留所有权利。
Chondrocytes isolated from human foetal epiphyseal cartilage were seeded dynamically into polyglycolic acid (PGA) scaffolds and cultured in recirculation column bioreactors to produce tissue-engineered cartilage. Several culture techniques with the potential to provide endogenous growth factors and other conditions beneficial for de novo cartilage synthesis were investigated. Osteochondral composite constructs were generated by seeding separate PGA scaffolds with either foetal chondrocytes or foetal osteoblasts then suturing the scaffolds together before bioreactor cultivation. This type of co-culture system provided direct contact between the tissue-engineered cartilage and developing tissue-engineered bone and yielded significant improvements in cartilage quality. In the cartilage section of the composites, the concentrations of glycosaminoglycan (GAG) and total collagen were increased by 55% and 2.5-fold, respectively, compared with control cartilage cultures, while levels of collagen type 11 were similar to those in the controls. The osteochondral composites were harvested from the bioreactors as single units with good integration between the cartilage and bone tissues. Only the cartilage layer contained GAG while only the bone layer was mineralised. In other experiments, co-culture of tissue-engineered cartilage with pieces of ex-vivo cartilage or ex-vivo bone did not improve the quality of the cartilage relative to control cultures. Addition of 10(-6) m diacerein to the culture medium also had no effect on the properties of engineered cartilage. This work demonstrates the beneficial effects of generating cartilage tissues in contact with developing bone. It also demonstrates the feasibility of producing composite osteochondral constructs for clinical application using recirculation column bioreactors. (c) 2005 Elsevier Ltd. All rights reserved.