Incorporation of tissue-specific molecules alters chondrocyte metabolism and gene expression in photocrosslinked hydrogels

Hydrogels are highly swollen, insoluble networks which can entrap chondrocytes and provide a 3-D environment necessary for the re-growth of cartilaginous tissue. In this study, hydrogels were formulated with a synthetic poly(ethylene glycol) (PEG) component to provide control over the macroscopic gel properties and from a cartilage specific compound, chondroitin sulfate (ChSA), to capture features of the chondrocytes' native environment. PEG was chosen as the base hydrogel chemistry, because it forms a 3-D environment that maintains chondrocyte function. ChSA, a highly negatively charged main component of proteoglycans, was then selectively incorporated into the PEG gel. Macroscopic gel properties were manipulated to obtain high compressive moduli coupled with a high degree of swelling by formulating copolymer gels with these chemistries. The gel compressive modulus of cell-free PEG gels increased from 34 to 140 kPa with the incorporation of ChSA for similar degrees of swelling. When chondrocytes were encapsulated in pure ChSA gels, synthesis of collagen and glycosaminoglycans was inhibited. However, when PEG was introduced into the copolymer gels, both extracellular matrix components were stimulated. Total collagen content increased from non-detectable in the pure ChSA gels to 0.48 ± 0.05 mg/g wet weight in the copolymer gels (40/60 ChSA/PEG). Gene expression for collagen type II was also enhanced by the incorporation of PEG into the gel, illustrating an important influence of gel chemistry on chondrocyte function; however, aggrecan gene expression was unaffected. This study demonstrates that the macroscopic properties of chondrocyte gel carriers can be controlled through the incorporation of charge into networks by ChSA, but the neutral, non-interactive base PEG chemistry facilitates extracellular matrix deposition.