The bioactivity of agarose-PEGDA interpenetrating network hydrogels with covalently immobilized RGD peptides and physically entrapped aggrecan.
The bioactivity of agarose-PEGDA interpenetrating network hydrogels with covalently immobilized RGD peptides and physically entrapped aggrecan.
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DOI：
10.1016/j.biomaterials.2014.01.002
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发表时间：
2014-04
期刊：
影响因子：
14
通讯作者：
Detamore, Michael S.
中科院分区：
文献类型：
--
作者：
Ingavle, Ganesh C.;Gehrke, Stevin H.;Detamore, Michael S.
关键词：
我们之前关于互穿网络(IPN)的报告表明，相对于单独的组成网络，在保持被包裹细胞的生存能力的同时，机械性能有了显著的改善。本研究考察了RGD与聚乙二醇二丙烯酸酯(PEGDA)网络的共价连接是否可以改善琼脂糖聚乙二醇二丙烯酸酯(PEGDA)网络的细胞活力和性能，与未修饰的IPN(对照)和不同浓度的物理包裹聚集素的IPN相比，提供了一个与以前工作的比较点。RGD或aggrecan的加入通常不会对机械性能产生不利影响，并显著改善软骨细胞的活性和性能。虽然4和100μg/mLaggrecan均能提高软骨细胞的活力，但只有100μg/mLaggrecan对细胞的生物合成有明显的促进作用，而100μg/mLRGD对软骨细胞的活力和生物合成均有明显的促进作用。有趣的是，观察到RGD和较高的aggrecan浓度的IPN内的细胞聚集，可能表明细胞迁移和/或优先的区域增殖。与其他综合方案网络相比，这种组合明显增强了基质的产量。随着细胞的迁移，我们还观察到了IPN外围以外的显著细胞增殖和基质合成，这可能对促进体内与周围软骨的整合具有重要意义。由于RGD和aggrecan(在较高浓度下)在细胞性能方面提供了实质性和可比的改进，RGD将是这种特定的IPN配方和细胞来源的推荐生物活性信号，因为它在商业化中节省了大量的成本和潜在的更直接的调控途径。
Our previous reports of interpenetrating networks (IPNs) have demonstrated drastic improvements in mechanical performance relative to individual constituent networks while maintaining viability of encapsulated cells. The current study investigated whether covalent linkage of RGD to the poly(ethylene glycol) diacrylate (PEGDA) network could improve upon cell viability and performance of agarose-PEGDA IPNs compared to unmodified IPNs (control) and to IPNs with different concentrations of physically entrapped aggrecan, providing a point of comparison to previous work. The inclusion of RGD or aggrecan generally did not adversely affect mechanical performance, and significantly improved chondrocyte viability and performance. Although both 4 and 100 μ g/mL of aggrecan improved cell viability, only 100 μ g/mL aggrecan was clearly beneficial to improving biosynthesis, whereas 100 μg/mL of RGD was beneficial to both chondrocyte viability and biosynthesis. Interestingly, clustering of cells within the IPNs with RGD and the higher aggrecan concentration were observed, likely indicating cell migration and/or preferred regional proliferation. This clustering resulted in a clearly visible enhancement of matrix production compared to the other IPNs. With this cell migration, we also observed significant cell proliferation and matrix synthesis beyond the periphery of the IPN, which could have important implications in facilitating integration with surrounding cartilage in vivo. With RGD and aggrecan (at its higher concentration) providing substantial and comparable improvements in cell performance, RGD would be the recommended bioactive signal for this particular IPN formulation and cell source given the significant cost savings and potentially more straightforward regulatory pathway in commercialization.
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DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
3.7
作者：
Ingavle, Ganesh C.;Dormer, Nathan H.;Gehrke, Stevin H.;Detamore, Michael S.
通讯作者：
Detamore, Michael S.
影响因子：
29.4
作者：
Gong, JP;Katsuyama, Y;Osada, Y
通讯作者：
Osada, Y
影响因子：
--
作者：
Deng, Ying;Hu, Jerry C.;Athanasiou, Kyriacos A.
通讯作者：
Athanasiou, Kyriacos A.
影响因子：
14
作者：
Hwang, Nathaniel S.;Varghese, Shyni;Elisseeff, Jennifer
通讯作者：
Elisseeff, Jennifer