One of main challenges in developing clinically relevant engineered cartilage is overcoming limited nutrient diffusion due to progressive elaboration of extracellular matrix at the periphery of the construct. Macro-channels have been used to decrease the nutrient path-length; however, the channels become occluded with matrix within weeks in culture, reducing nutrient diffusion. Alternatively, microparticles can be imbedded throughout the scaffold to provide localized nutrient delivery. In this study, we evaluated biocompatibility of polysebacic anhydride (PSA) polymers and the effectiveness of PSA-based microparticles for short-term delivery of nutrients in engineered cartilage. PSA-based microparticles were biocompatible with juvenile bovine chondrocytes for concentrations up to 2mg/mL; however, cytotoxicity was observed at 20mg/mL. Cytotoxicity at high concentrations is likely due to intracellular accumulation of PSA degradation products and resulting lipotoxicity. Cytotoxicity of PSA was partially reversed in the presence of bovine serum albumin. In conclusion, the findings from this study demonstrate concentration-dependent biocompatibility of PSA-based microparticles and potential application as a nutrient delivery vehicle that can be imbedded in scaffolds for tissue engineering.

The harsh inflammatory environment associated with injured and arthritic joints represents a major challenge to articular cartilage repair. In this study, we report the effect of cerium oxide nanoparticles, or nanoceria, in modulating development of engineered cartilage and in combating the deleterious effects of interleukin-1α. Nanoceria was found to be biocompatible with bovine chondrocytes up to a concentration of 1000 μg/mL (60,000 cells/μg of nanoceria), and its presence significantly improved compressive mechanical properties and biochemical composition (i.e., glycosaminoglycans) of engineered cartilage. Raman microspectroscopy revealed that individual chondrocytes with internalized nanoceria have increased concentrations of proline, procollagen, and glycogen as compared with cells without the nanoparticles in their vicinity. The inflammatory response due to physiologically relevant quantities of interluekin-1α (0.5 ng/mL) is partially inhibited by nanoceria. To the best of the authors' knowledge, these results are the first to demonstrate a high potential for nanoceria to improve articular cartilage tissue properties and for their long-term treatment against an inflammatory reaction.