Hierarchically structured, hyaluronic acid-based hydrogel matrices via the covalent integration of microgels into macroscopic networks.

ABSTRACT: 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.

SUBMITTER: Jha AK 

PROVIDER: S-EPMC2950657 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature