Injectable thermo-responsive hydrogels capable of cell- and tissue-specific interactions

Articular cartilage demonstrates extremely limited regenerative capabilities, and traditional methods used to treat articular cartilage defects fail to restore normal tissue function. Currently, alternative methods for treatment focus on the use of three-dimensional polymer scaffolds to direct the regeneration of articular cartilage. However, many of these scaffolds suffer from limitations that compromise their clinical utility.; In an effort to improve upon existing scaffold designs, this thesis describes the development of injectable thermo-responsive hydrogels and semi-interpenetrating polymer networks (semi-IPNs) for use in articular cartilage regeneration applications. The hydrogels consisted of loosely cross-linked networks of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc), and the semi-IPNs were composed of poly(NIPAAm- co-AAc) [P(NIPAAm-co-AAc)] hydrogels with linear P(AAc) chains physically-entangled within the network. The P(NIPAAm)-based component of the design was chosen specifically, due to the unique phase behavior demonstrated by P(NIPAAm)-based materials in aqueous media.; The P(NIPAAm-co-AAc) hydrogels were injectable through a small diameter aperture at 22°C and exhibited a significant increase in rigidity when heated to body temperature (i.e., 37°C). Importantly, the P(NIPAAm-co-AAc) hydrogels supported bovine articular chondrocyte viability and promoted articular cartilage-like tissue formation in vitro.; In the P(NIPAAm-co-AAc)-based semi-IPN studies, the materials were extensively characterized. The effects of the linear P(AAc) chains on semi-IPN injectability, lower critical solution temperature (LCST), volume change, and rheology were examined. In general, the P(AAc) chains did not affect the LCST, volume change, or 22°C rigidity of the semi-IPNs, as compared to P(NIPAAm-co-AAc) hydrogels. However, as the P(AAc) chain amount increased, the semi-IPN injectability decreased. Notably, at 37°C, the P(NIPAAm-co-AAc)-based semi-IPNs were significantly more rigid than the P(NIPAAm-co-AAc) hydrogels.; Test methods were developed to examine the adhesive interactions between peptide-modified semi-IPNs and a model of the articular cartilage extracellular matrix (ECM) [i.e., hyaluronic acid-grafted (HA-grafted) glass substrates]. P(AAc) chains in the P(NIPAAm-co-AAc)-based semi-IPNs were functionalized with synthetic peptides that adhere to HA. At 22°C, the peptide-functionalized semi-IPNs demonstrated significantly greater adhesion to the HA-grafted substrates than non-functionalized semi-IPNs. Based on the results presented in this thesis, these P(NIPAAm-co-AAc)-based matrices have the potential to serve as functional scaffolds in tissue engineering applications.