In situ forming hydrogels composed of oxidized high molecular weight hyaluronic acid and gelatin for nucleus pulposus regeneration

被引:92
作者
Chen, Yu-Chun [1 ,2 ,3 ]
Su, Wen-Yu [1 ,2 ,3 ]
Yang, Shu-Hua [4 ,5 ]
Gefen, Amit [6 ]
Lin, Feng-Huei [1 ,2 ,3 ]
机构
[1] Natl Taiwan Univ, Coll Engn, Inst Biomed Engn, Taipei 10764, Taiwan
[2] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan
[3] Natl Hlth Res Inst, Div Med Engn Res, Zhunan, Miaoli County, Taiwan
[4] Natl Taiwan Univ, Coll Med, Dept Orthoped, Taipei 10764, Taiwan
[5] Natl Taiwan Univ Hosp, Taipei, Taiwan
[6] Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel
关键词
Gelatin; Gene expression; Hyaluronic acid; Nucleus pulposus; Viscoelastic properties; INTERVERTEBRAL DISC; CELLS; PROTEOGLYCANS; DECORIN; BACK; TRANSLOCATION; BIGLYCAN; SURGERY; CULTURE;
D O I
10.1016/j.actbio.2012.09.039
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Encapsulation of nucleus pulposus (NP) cells within in situ forming hydrogels is a novel biological treatment for early stage intervertebral disc degeneration. The procedure aims to prolong the life of the degenerating discs and to regenerate damaged tissue. In this study we developed an injectable oxidized hyaluronic acid-gelatin-adipic acid dihydrazide (oxi-HAG-ADH) hydrogel. High molecular weight (1900 kDa) hyaluronic acid was crosslinked with various concentrations of gelatin to synthesize the hydrogels and their viscoelastic properties were analyzed. Interactions between the hydrogels, NP cells, and the extracellular matrix (ECM) were also evaluated, as were the effects of the hydrogels on NP cell gene expression. The hydrogels possess several clinical advantages, including sterilizability, low viscosity for injection, and ease of use. The viscoelastic properties of the hydrogels were similar to native tissue, as reflected in the complex shear modulus (similar to 11-14 kPa for hydrogels, 11.3 kPa for native NP). Cultured NP cells not only attached to the hydrogels but also survived, proliferated, and maintained their round morphology. Importantly, we found that hydrogels increased NP cell expression of several crucial ECM-related genes, such as COL2A1, AGN, SOX-9, and HIF-1A. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:5181 / 5193
页数:13
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