Department of Bioengineering, Hanyang University, Seoul 04763, Republic of Korea.
Department of Bioengineering, Hanyang University, Seoul 04763, Republic of Korea; Institute of Nano Science and Technology, Hanyang University, Seoul 04763, Republic of Korea.
Carbohydr Polym. 2018 Oct 1;197:422-430. doi: 10.1016/j.carbpol.2018.06.016. Epub 2018 Jun 5.
Hyaluronate-based hydrogels have been widely exploited as synthetic extracellular matrices in many tissue engineering applications, including cartilage tissue engineering. Hyaluronate-based hydrogels are typically prepared by chemical cross-linking reactions, in which chemical reagents may induce side effects, unless they are completely removed after the cross-linking reaction. We thus suggest the utilization of hybrid materials composed of hyaluronate as a main chain and alginate for physical cross-linking to simply form hydrogels in the presence of calcium ions under physiological conditions. In this study, we hypothesized that the introduction of biomimetic peptides to hyaluronate-alginate hybrid (HAH) hydrogels could be useful to regulate the chondrocyte phenotype, including chondrogenic differentiation. HAH was modified with the arginine-glycine-aspartate (RGD) peptide as a cell-matrix interaction motif and/or histidine-alanine-valine (HAV) as a cell-cell interaction motif. The HAV peptide is known to bind to cadherin, which is a key factor involved in homophilic cell-cell interactions as well as chondrogenesis. The viability and growth of mouse chondrocytes (ATDC5 cells) increased significantly when cultured on RGD-modified HAH hydrogels. Cell aggregates formed on HAV-modified HAH hydrogels, resulting in enhanced chondrogenic differentiation via enhanced cell-cell interactions by HAV modification. Interestingly, a synergistic effect of HAV and RGD peptides within HAH hydrogels on chondrogenesis was found in 3-D experiments in vitro. This approach to utilizing physically cross-linkable hyaluronate-based hydrogels presenting biomimetic peptides has potential applications in tissue engineering, including cartilage regeneration.
基于透明质酸的水凝胶已被广泛应用于许多组织工程应用中，包括软骨组织工程，作为合成细胞外基质。基于透明质酸的水凝胶通常通过化学交联反应制备，其中化学试剂可能会引起副作用，除非在交联反应后完全去除。因此，我们建议利用透明质酸作为主链和海藻酸盐组成的杂化材料进行物理交联，在生理条件下钙离子存在下简单形成水凝胶。在这项研究中，我们假设将仿生肽引入透明质酸-海藻酸盐杂化（HAH）水凝胶中可能有助于调节软骨细胞表型，包括软骨分化。HAH 被 Arg-Gly-Asp（RGD）肽修饰为细胞-基质相互作用基序和/或 His-Ala-Val（HAV）肽作为细胞-细胞相互作用基序。HAV 肽已知与钙粘蛋白结合，钙粘蛋白是参与同源细胞间相互作用以及软骨发生的关键因素。当在 RGD 修饰的 HAH 水凝胶上培养时，小鼠软骨细胞（ATDC5 细胞）的活力和生长显著增加。在 HAV 修饰的 HAH 水凝胶上形成细胞聚集体，通过 HAV 修饰增强细胞-细胞相互作用从而增强软骨分化。有趣的是，在体外 3D 实验中发现 HAV 和 RGD 肽在 HAH 水凝胶中的协同作用对软骨形成有影响。这种利用具有仿生肽的可物理交联透明质酸水凝胶的方法在组织工程中具有应用潜力，包括软骨再生。
