Elastin based cell-laden injectable hydrogels with tunable gelation, mechanical and biodegradation properties

摘要

Injectable hydrogels made from extracellular matrix proteins such as elastin show great promise for various biomedical applications. Use of cytotoxic reagents, fixed gelling behavior, and lack of mechanical strength in these hydrogels are the main associated drawbacks. The aim of this study was to develop highly cytocompatible and injectable elastin-based hydrogels with alterable gelation characteristics, favorable mechanical properties and structural stability for load bearing applications. A thermoresponsive copolymer, poly(N-isopropylacrylamide-co-polylactide-2-hydroxyethyl methacrylate-co-oligo(ethylene glycol)monomethyl ether methacrylate, was functionalized with succinimide ester groups by incorporating N-acryloxysuccinimide monomer. These ester groups were exploited to covalently bond this polymer, denoted as PNPHO, to different proteins with primary amine groups such as α-elastin in aqueous media. The incorporation of elastin through covalent bond formation with PNPHO promotes the structural stability, mechanical properties and live cell proliferation within the structure of hydrogels. Our results demonstrated that elastin-co-PNPHO solutions were injectable through fine gauge needles and converted to hydrogels in situ at 37°C in the absence of any crosslinking reagent. By altering PNPHO content, the gelling time of these hydrogels can be finely tuned within the range of 2-15min to ensure compatibility with surgical requirements. In addition, these hydrogels exhibited compression moduli in the range of 40-145kPa, which are substantially higher than those of previously developed elastin-based hydrogels. These hydrogels were highly stable in the physiological environment with the evidence of 10wt% mass loss in 30 days of incubation in a simulated environment. This class of hydrogels is invivo bioabsorbable due to the gradual increase of the lower critical solution temperature of the copolymer to above 37°C due to the cleavage of polylactide from the PNPHO copolymer. Moreover, our results demonstrated that more than 80% of cells encapsulated in these hydrogels remained viable, and the number of encapsulated cells increased for at least 5 days. These unique properties mark elastin-co-PNHPO hydrogels as favorable candidates for a broad range of tissue engineering applications.