Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle

Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle
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DOI:
10.1016/j.joca.2004.12.001
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发表时间:
2005-04-01
影响因子:
7
通讯作者:
Buschmann, MD
Buschmann, MD
中科院分区:
医学2区
文献类型:
--
作者:
Hoemann, CD;Sun, J;Buschmann, MD

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目的:成人关节软骨对创伤性损伤的内在修复反应有限。要再生受损的软骨,细胞辅助修复,因此被视为一个有前途的治疗,尽管受到限制的缺乏一个合适的技术来提供和保留软骨细胞在defect location.Design:我们已经开发了一种细胞相容性壳聚糖解决方案,是空间填充,凝胶在几分钟内,并坚持软骨和骨原位。这种独特的特性组合表明其作为关节镜下可注射的细胞辅助软骨修复载体的巨大潜力。本研究的主要目的是评估该聚合物系统在加载有原代关节软骨细胞时在体外和体内支持软骨形成的能力。将壳聚糖凝胶在体外培养,有和没有软骨细胞,以及皮下注射在裸鼠形成皮下背植入物。在体外和体内的结构进行了集体组织学分析,软骨细胞的mRNA和蛋白质的表达,糖胺聚糖,胶原蛋白,和DNA的生化水平,并为mechanical properties.Results:所得的组织结构揭示了组织化学,生化和机械性能相媲美,在体外观察到的原代软骨细胞培养在2%琼脂糖。此外,凝胶被保留后注射到一个手术准备,兔全层软骨缺损后1天在体内,在兔骨软骨缺损,长达1 week.Conclusions:在原位凝胶壳聚糖溶液中描述的可以支持在体外和体内积累的软骨基质的初级软骨细胞,而坚持在骨软骨缺损至少1周在体内。(c)2004年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Adult articular cartilage shows a limited intrinsic repair response to traumatic injury. To regenerate damaged cartilage, cell-assisted repair is thus viewed as a promising therapy, despite being limited by the lack of a suitable technique to deliver and retain chondrogenic cells at the defect site.Design: We have developed a cytocompatible chitosan solution that is space-filling, gels within minutes, and adheres to cartilage and bone in situ. This unique combination of properties suggested significant potential for its use as an arthroscopically injectable vehicle for cell-assisted cartilage repair. The primary goal of this study was to assess the ability of this polymer system, when loaded with primary articular chondrocytes, to support cartilage formation in vitro and in vivo. The chitosan gel was cultured in vitro, with and without chondrocytes, as well as injected subcutaneously in nude mice to form subcutaneous dorsal implants. In vitro and in vivo constructs were collectively analyzed histologically, for chondrocyte mRNA and protein expression, for biochemical levels of glycosaminoglycan, collagen, and DNA, and for mechanical properties.Results: Resulting tissue constructs revealed histochemical, biochemical and mechanical properties comparable to those observed in vitro for primary chondrocytes cultured in 2% agarose. Moreover, the gel was retained after injection into a surgically prepared, rabbit full-thickness chondral defect after 1 day in vivo, and in rabbit osteochondral defects, up to 1 week.Conclusions: The in situ-gelling chitosan solution described here can support in vitro and in vivo accumulation of cartilage matrix by primary chondrocytes, while persisting in osteochondral defects at least 1 week in vivo. (c) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.