Hierarchically structured, hyaluronic acid-based hydrogel matrices via the covalent integration of microgels into macroscopic networks.
Hierarchically structured, hyaluronic acid-based hydrogel matrices via the covalent integration of microgels into macroscopic networks.
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DOI：
10.1039/c0sm00101e
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发表时间：
2010-06-15
期刊：
影响因子：
3.4
通讯作者：
Jia X
中科院分区：
文献类型：
--
作者：
Jha AK;Malik MS;Farach-Carson MC;Duncan RL;Jia X
我们的目标是开发仿生水凝胶基质，不仅表现出结构层次和机械完整性，但也目前在一个可控的方式生物线索。为此，通过反相乳液交联过程，然后用甲基丙烯酸缩水甘油酯（GMA）进行化学改性，合成了可光交联的基于透明质酸（HA）的水凝胶颗粒（HGP）。采用GMA改性的HA（HA-GMA）作为可溶性大分子单体。通过自由基聚合制备了含有共价结合的水凝胶颗粒（HA-c-HGP）的宏观水凝胶。水凝胶颗粒和二级HA基质之间的共价键导致在颗粒周围形成扩散的纤维状界面。与传统的HA-GMA光交联法制备的本体凝胶相比，该水凝胶具有较低的溶胶分数和较低的平衡溶胀比。当在单轴压缩下测试时，HA-c-HGP凝胶比HA-p-HGP凝胶更柔韧，并且在比HA-GMA凝胶更高的应变下断裂。原代牛软骨细胞被光包裹在HA基质中，细胞损伤最小。由HA-GMA和HA HGP创建的3D微环境不仅维持软骨细胞表型，而且促进软骨特异性细胞外基质的产生。为了进一步提高HA-c-HGP凝胶的生物活性，将骨形态发生蛋白2（BMP-2）负载到固定化的HGP中。BMP-2以受控方式从HA-c-HGP凝胶中释放，在延长的时间段内具有减少的初始爆发。HA-c-HGP凝胶是用于软骨组织工程的生物活性基质的有希望的候选者。
We aimed to develop biomimetic hydrogel matrices that not only exhibit structural hierarchy and mechanical integrity, but also present biological cues in a controlled fashion. To this end, photocrosslinkable, hyaluronic acid (HA)-based hydrogel particles (HGPs) were synthesized via an inverse emulsion crosslinking process followed by chemical modification with glycidyl methacrylate (GMA). HA modified with GMA (HA-GMA) was employed as the soluble macromer. Macroscopic hydrogels containing covalently integrated hydrogel particles (HA-c-HGP) were prepared by radical polymerization of HA-GMA in the presence of crosslinkable HGPs. The covalent linkages between the hydrogel particles and the secondary HA matrix resulted in the formation of a diffuse, fibrilar interface around the particles. Compared to the traditional bulk gels synthesized by photocrosslinking of HA-GMA, these hydrogels exhibited a reduced sol fraction and a lower equilibrium swelling ratio. When tested under uniaxial compression, the HA-c-HGP gels were more pliable than the HA-p-HGP gels and fractured at higher strain than the HA-GMA gels. Primary bovine chondrocytes were photoencapsulated in the HA matrices with minimal cell damage. The 3D microenvironment created by HA-GMA and HA HGPs not only maintained the chondrocyte phenotype but also fostered the production of cartilage specific extracellular matrix. To further improve the biological activities of the HA-c-HGP gels, bone morphogenetic protein 2 (BMP-2) was loaded into the immobilized HGPs. BMP-2 was released from the HA-c-HGP gels in a controlled manner with reduced initial burst over prolonged periods of time. The HA-c-HGP gels are promising candidates for use as bioactive matrices for cartilage tissue engineering.