Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Tissue Eng Part A. 2010 Sep;16(9):2915-25. doi: 10.1089/ten.TEA.2010.0096.
Biocompatible polymers capable of photopolymerization are of immense interest for tissue engineering applications as they can be injected in a minimally invasive manner into a defect site and, then upon application of ultraviolet light, rapidly form hydrogels in situ. Cell adhesion interactions with a biomaterial are known to be important in regulating cell behaviors such as proliferation and differentiation. Therefore, we have covalently modified photocrosslinkable alginate with cell adhesion ligands containing the Arg-Gly-Asp amino acid sequence to form biodegradable, photocrosslinked alginate hydrogels with controlled cell adhesivity. This unique polymer system allows for independent modulation of the physical and biochemical signaling environment presented to cells. The physical properties of the hydrogels such as elastic moduli, swelling ratios, and degradation profiles were similar at the same crosslinking density regardless of the presence of adhesion ligands. Chondrocytes seeded on the surface of the adhesion ligand-modified hydrogels were able to attach and spread, whereas those seeded on unmodified hydrogels exhibited minimal adherence. Importantly, the adhesion-ligand-modified hydrogels enhanced the proliferation and chondrogenic differentiated function of encapsulated chondrocytes as demonstrated by increased DNA content and production of glycosaminoglycans compared to unmodified control hydrogels. This new photocrosslinkable, biodegradable biomaterial system in which the soluble (e.g., growth factors) and insoluble (e.g., cell adhesion ligands) biochemical signaling environment and the biomaterial physical properties (e.g., the elastic moduli) can be independently controlled may be a powerful tool for elucidating the individual and combined effects of these parameters on cell function for cartilage tissue engineering and other regenerative medicine applications.
具有光聚合能力的生物相容性聚合物在组织工程应用中具有巨大的兴趣，因为它们可以以微创的方式注入缺陷部位，然后在应用紫外光时，迅速在原位形成水凝胶。已知生物材料与细胞的粘附相互作用在调节细胞行为（如增殖和分化）方面非常重要。因此，我们已经将光交联海藻酸盐与含有精氨酸-甘氨酸-天冬氨酸氨基酸序列的细胞粘附配体共价修饰，以形成具有可控细胞粘附性的可生物降解的光交联海藻酸盐水凝胶。这种独特的聚合物系统允许独立调节呈现给细胞的物理和生化信号环境。水凝胶的物理性质，如弹性模量、溶胀比和降解曲线，在相同的交联密度下，无论是否存在粘附配体，都相似。在粘附配体修饰的水凝胶表面上接种的软骨细胞能够附着和扩展，而在未修饰的水凝胶上接种的细胞则表现出最小的粘附性。重要的是，与未修饰的对照水凝胶相比，粘附配体修饰的水凝胶增强了包封的软骨细胞的增殖和软骨分化功能，表现为 DNA 含量增加和糖胺聚糖的产生增加。这种新的可光交联的、可生物降解的生物材料系统，其中可溶的（例如生长因子）和不可溶的（例如细胞粘附配体）生化信号环境以及生物材料的物理性质（例如弹性模量）可以独立控制，可能是阐明这些参数对软骨组织工程和其他再生医学应用中细胞功能的单独和联合影响的有力工具。
