Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0412, USA.
Pharm Res. 2011 Jun;28(6):1422-30. doi: 10.1007/s11095-011-0378-9. Epub 2011 Feb 18.
In this study, we evaluated the effect of hydrogel structural properties on proliferation and biosynthesis activity of encapsulated chondrocytes.
Hydrogels with varying structural and mechanical properties were prepared by photopolymerizing PEGDA precursors having MWs of 3.4 kDa, 6 kDa, 10 kDa, and 20 kDa and were characterized for their swelling ratio, network structure, morphology, and mechanical properties. The effect of hydrogel structural properties on the cellular activity of encapsulated chondrocytes was studied over four weeks.
Varying the molecular weight of PEGDA precursors exhibited a significant effect on the structural and mechanical properties of the hydrogels. Large mesh size was found to support cell proliferation. However, extracellular matrix (ECM) accumulation varied with the precursor molecular weight. Both PEGDA 6 kDa and 10 kDa hydrogels supported GAG accumulation, while PEGDA 10 kDa and 20 KDa hydrogels supported collagen accumulation. Chondrocytes cultured in PEGDA 10 kDa hydrogels expressed a relative increase in collagen type II and aggrecan expression while maintaining low collagen type I expression.
Increasing mesh size of the hydrogels resulted in an increase in cellular proliferation exhibiting the strong correlation between mesh size and cell growth, while mesh size had a differential effect on ECM accumulation and expression of cartilage specific markers.
本研究评估了水凝胶结构特性对包封软骨细胞增殖和生物合成活性的影响。
通过光聚合具有 3.4 kDa、6 kDa、10 kDa 和 20 kDa MW 的 PEGDA 前体来制备具有不同结构和机械性能的水凝胶,并对其溶胀比、网络结构、形态和机械性能进行了表征。研究了水凝胶结构特性对包封软骨细胞细胞活性的影响,为期四周。
改变 PEGDA 前体的分子量对水凝胶的结构和机械性能有显著影响。大的网格尺寸被发现支持细胞增殖。然而,细胞外基质(ECM)的积累随前体分子量而变化。PEGDA 6 kDa 和 10 kDa 水凝胶均支持 GAG 积累,而 PEGDA 10 kDa 和 20 kDa 水凝胶支持胶原积累。在 PEGDA 10 kDa 水凝胶中培养的软骨细胞表达相对增加的 II 型胶原和聚集蛋白聚糖表达,同时保持低的 I 型胶原表达。
增加水凝胶的网格尺寸会导致细胞增殖增加,表现出网格尺寸与细胞生长之间的强相关性,而网格尺寸对 ECM 积累和软骨特异性标志物的表达有差异影响。