Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan.
Acta Biomater. 2013 Feb;9(2):5181-93. doi: 10.1016/j.actbio.2012.09.039. Epub 2012 Oct 4.
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 (∼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.
核髓细胞（NP）细胞的包封在原位形成水凝胶中是一种治疗早期椎间盘退变的新型生物治疗方法。该方法旨在延长退变椎间盘的寿命并再生受损组织。在本研究中，我们开发了一种可注射的氧化透明质酸-明胶-己二酸二酰肼（oxi-HAG-ADH）水凝胶。高分子量（1900 kDa）透明质酸与不同浓度的明胶交联以合成水凝胶，并分析其粘弹性。还评估了水凝胶与 NP 细胞和细胞外基质（ECM）之间的相互作用，以及水凝胶对 NP 细胞基因表达的影响。该水凝胶具有许多临床优势，包括可消毒性、注射用低粘度和易于使用。水凝胶的粘弹性类似于天然组织，反映在复合剪切模量（水凝胶为 11-14 kPa，天然 NP 为 11.3 kPa）。培养的 NP 细胞不仅可以附着在水凝胶上，而且还可以存活、增殖并保持其圆形形态。重要的是，我们发现水凝胶增加了 NP 细胞表达几种关键的 ECM 相关基因，如 COL2A1、AGN、SOX-9 和 HIF-1A。
