用于关节软骨工程的热可逆水凝胶支架

Thermoreversible hydrogel scaffolds for articular cartilage engineering.

作者信息

Fisher John P, Jo Seongbong, Mikos Antonios G, Reddi A Hari

机构信息

Department of Orthopaedic Surgery, Center for Tissue Regeneration and Repair, School of Medicine, University of California-Davis, Research Building I, Room 2000, 4635 Second Avenue, Sacramento, CA 95817, USA.

出版信息

J Biomed Mater Res A. 2004 Nov 1;71(2):268-74. doi: 10.1002/jbm.a.30148.

Abstract

Articular cartilage has limited potential for repair. Current clinical treatments for articular cartilage damage often result in fibrocartilage and are associated with joint pain and stiffness. To address these concerns, researchers have turned to the engineering of cartilage grafts. Tissue engineering, an emerging field for the functional restoration of articular cartilage and other tissues, is based on the utilization of morphogens, scaffolds, and responding progenitor/stem cells. Because articular cartilage is a water-laden tissue and contains within its matrix hydrophilic proteoglycans, an engineered cartilage graft may be based on synthetic hydrogels to mimic these properties. To this end, we have developed a polymer system based on the hydrophilic copolymer poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)]. Solutions of this polymer are liquid below 25 degrees C and gel above 35 degrees C, allowing an aqueous solution containing cells at room temperature to form a hydrogel with encapsulated cells at physiological body temperature. The objective of this work was to determine the effects of the hydrogel components on the phenotype of encapsulated chondrocytes. Bovine articular chondrocytes were used as an experimental model. Results demonstrated that the components required for hydrogel fabrication did not significantly reduce the proteoglycan synthesis of chondrocytes, a phenotypic marker of chondrocyte function. In addition, chondrocyte viability, proteoglycan synthesis, and type II collagen synthesis within P(PF-co-EG) hydrogels were investigated. The addition of bone morphogenetic protein-7 increased chondrocyte proliferation with the P(PF-co-EG) hydrogels, but did not increase proteoglycan synthesis by the chondrocytes. These results indicate that the temperature-responsive P(PF-co-EG) hydrogels are suitable for chondrocyte delivery for articular cartilage repair.

摘要

关节软骨的自我修复能力有限。目前针对关节软骨损伤的临床治疗方法往往会形成纤维软骨,并伴有关节疼痛和僵硬。为了解决这些问题,研究人员已转向软骨移植工程。组织工程是一个用于关节软骨和其他组织功能修复的新兴领域,它基于形态发生素、支架和反应性祖细胞/干细胞的利用。由于关节软骨是一种富含水分的组织,其基质中含有亲水性蛋白聚糖,因此工程化软骨移植可以基于合成水凝胶来模拟这些特性。为此,我们开发了一种基于亲水性共聚物聚(富马酸丙酯 - 共 - 乙二醇)[P(PF - co - EG)]的聚合物体系。该聚合物溶液在25摄氏度以下为液体,在35摄氏度以上形成凝胶,这使得在室温下含有细胞的水溶液在生理体温下形成包封细胞的水凝胶。这项工作的目的是确定水凝胶成分对包封软骨细胞表型的影响。牛关节软骨细胞被用作实验模型。结果表明,水凝胶制备所需的成分不会显著降低软骨细胞的蛋白聚糖合成,而蛋白聚糖合成是软骨细胞功能的一个表型标志物。此外,还研究了P(PF - co - EG)水凝胶中软骨细胞的活力、蛋白聚糖合成和II型胶原合成。骨形态发生蛋白 - 7的添加增加了P(PF - co - EG)水凝胶中软骨细胞的增殖,但并未增加软骨细胞的蛋白聚糖合成。这些结果表明,温度响应性P(PF - co - EG)水凝胶适用于关节软骨修复的软骨细胞递送。

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