Thermo-Responsive Peptide-Modified Hydrogels for Tissue Regeneration

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Abstract
Loosely cross-linked hydrogels consisting of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) were synthesized, characterized, and used as model scaffolds for studying cell−material interactions in three-dimensions (3D). The AAc groups were functionalized with peptides containing the −RGD− and −FHRRIKA− sequences found in bone sialoprotein. Chemical modification of the hydrogels was verified via solid-state 1H nuclear magnetic resonance spectroscopy, lower critical solution temperature studies, and volume change studies. The peptide-modified hydrogels were pliable at 22 °C and could be injected through a small-diameter aperture. Rat calvarial osteoblasts (RCO) seeded into the peptide-modified hydrogels were viable for at least 21 days of in vitro culture. The RCO spread more and demonstrated significantly greater proliferation when cultured within the peptide-modified hydrogels, as compared to control hydrogels. These peptide-modified P(NIPAAm-co-AAc) hydrogels serve as useful tools for studying cell−material interactions within 3D structures and have the potential to be used as injectable scaffolds for tissue engineering applications.