An enzyme-sensitive PEG hydrogel based on aggrecan catabolism for cartilage tissue engineering

Abstract

A new cartilage-specific degradable hydrogel based on photoclickable thiol-ene poly(ethylene glycol) (PEG) hydrogels is presented. The hydrogel crosslinks are composed of the peptide, CRDTEGE-ARGSVIDRC, derived from the aggrecanase-cleavable site in aggrecan. This new hydrogel is evaluated for use in cartilage tissue engineering by encapsulating bovine chondrocytes from different cell sources (skeletally immature (juvenile) and mature (adult) donors and adult cells stimulated with proinflammatory lipopolysaccharide (LPS)) and culturing for 12 weeks. Regardless of cell source, a twofold decrease in compressive modulus is observed by 12 weeks, but without significant hydrogel swelling indicating limited bulk degradation. For juvenile cells, a connected matrix rich in aggrecan and collagen II, but minimal collagens I and X is observed. For adult cells, less matrix, but similar quality, is deposited. Aggrecanase activity is elevated, although without accelerating bulk hydrogel degradation. LPS further decreases matrix production, but does not affect aggrecanase activity. In contrast, matrix deposition in the nondegradable hydrogels consists of aggrecan and collagens I, II, and X, indicative of hypertrophic cartilage. Lastly, no inflammatory response in chondrocytes is observed by the aggrecanase-sensitive hydrogels. Overall, it is demonstrated that this new aggrecanase-sensitive hydrogel, which is degradable by chondrocytes and promotes a hyaline-like engineered cartilage, is promising for cartilage regeneration.

Keywords: biodegradation; cartilage tissue engineering; hydrogel; peptide; poly(ethylene glycol).