Delivery of TGF-beta1 and chondrocytes via injectable, biodegradable hydrogels for cartilage tissue engineering applications

In this work, novel hydrogel composites, based on the biodegradable polymer, oligo(poly(ethylene glycol) fumarate) (OPF) and gelatin microparticles (MPs) were utilized as injectable cell and growth factor carriers for cartilage tissue engineering applications. Specifically, bovine chondrocytes were embedded in composite hydrogels co-encapsulating gelatin MPs loaded with transforming growth factor-beta1 (TGF-beta1). Hydrogels with embedded cells co-encapsulating unloaded MPs and those with no MPs served as controls in order to assess the effects of MPs and TGF-beta1 on chondrocyte function. Samples were cultured up to 28 days in vitro. By 14 days, cell attachment to embedded gelatin MPs within the constructs was observed via light microscopy. Bioassay results showed that, over the 21 day period, there was a statistically significant increase in cellular proliferation for samples containing gelatin MPs, but no increase was exhibited in samples without MPs over the culture period. The release of TGF-beta1 further increased cell construct cellularity. Over the same time period, glycosaminoglycan content per cell remained constant for all formulations, suggesting that the dramatic increase in cell number for samples with TGF-beta1-loaded MPs was accompanied by maintenance of the cell phenotype. Overall, these data indicate the potential of OPF hydrogel composites containing embedded chondrocytes and TGF-beta1-loaded gelatin MPs as a novel strategy for cartilage tissue engineering.