Influence of hyaluronic acid modification on CD44 binding towards the design of hydrogel biomaterials
Influence of hyaluronic acid modification on CD44 binding towards the design of hydrogel biomaterials
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DOI：
10.1016/j.biomaterials.2019.119451
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发表时间：
2019-11-01
期刊：
影响因子：
14
通讯作者：
Burdick, Jason A.
中科院分区：
文献类型：
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作者：
Kwon, Mi Y.;Wang, Chao;Burdick, Jason A.
透明质酸（HA）是D-葡糖醛酸和N-乙酰基-D-葡糖胺的线性多糖，其天然存在于许多组织中并通过细胞表面受体（例如，CD44）。HA作为一种化学改性的大分子单体已被广泛研究，用于交联成生物材料，如水凝胶和大孔支架。然而，HA修饰的程度和类型对其与CD 44结合的影响还没有很好地理解或量化。为了解决这个问题，我们在羧酸或伯醇处用各种化学基团（例如，降冰片烯、甲基丙烯酸酯）和量级（类似于10、20或40%的二糖），然后表征可溶性和水凝胶形式的结合。HA与固定在板上或由细胞呈递的CD 44的结合受到其修饰的程度和类型的影响，其中增加的修饰（即，约40%）通常降低结合。通过原子力显微镜测量的CD 44修饰的珠与水凝胶的粘附揭示了类似的趋势，特别是与羧酸的疏水修饰的粘附降低。此外，间充质基质细胞的软骨形成时，封装在水凝胶制成的改性HA大分子单体在高改性减少，表现类似于惰性水凝胶对照。这项工作表明，多糖的改性的类型和程度是重要的因素，应考虑在保持其生物功能时，加工成水凝胶。
Hyaluronic acid (HA) is a linear polysaccharide of D-glucuronic acid and N-acetyl-D-glucosamine that is native to many tissues and interacts with cells via cell-surface receptors (e.g., CD44). HA has been extensively explored as a chemically-modified macromer for crosslinking into biomaterials, such as hydrogels and macroporous scaffolds. However, the influence of the extent and type of HA modification on its binding to CD44 is not well understood or quantified. To address this, we modified HA at either the carboxylic acid or the primary alcohol with various chemical groups (e.g., norbomenes, methacrylates) and magnitudes (similar to 10, 20, or 40% of disaccharides) and then characterized binding in both soluble and hydrogel forms. HA binding to CD44 immobilized on plates or presented by cells was influenced by the extent and type of its modification, where increased modification (i.e., similar to 40%) generally decreased binding. The adhesion of CD44-modified beads to hydrogels as measured by atomic force microscopy revealed a similar trend, particularly with decreased adhesion with hydrophobic modifications to the carboxylic acid. Further, the chondrogenesis of mesenchymal stromal cells when encapsulated in hydrogels fabricated from modified HA macromers was reduced at high modification, behaving similarly to inert hydrogel controls. This work suggests that the types and extents of modification of polysaccharides are important factors that should be considered in preserving their biological function when processed as hydrogels.