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Novel, bioerodible, thermosensitive poly(NIPAAm-co-dimethyl–γ-butyrolactone), with hydrolysis-dependent thermosensitivity, were synthesized by radical polymerization with varying dimethyl-γ-butyrolactone content and the properties of the copolymers were characterized using Differential Scanning Calorimetry (DSC), High Performance Liquid Chromatography (HPLC) in conjunction with Static Light Scattering, Fourier Transformed Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and acid titration. The lower critical solution temperature (LCST) of the copolymers decreased with increasing dimethyl-γ-butyrolactone content, but then increased after ring-opening hydrolysis of the dimethyl-γ-butyrolactone side group. FTIR and NMR spectra showed the copolymerization of these two monomers and the hydrolysis-dependent ring-opening of the dimethyl-γ-butyrolactone side group. It was also found that there are no low-molecular-weight by-products but rather dissolution of the polymer chains at 37°C during the time frame of application. Models of the kinetics suggest that the hydrolysis reaction is self-catalytic due to an increase in hydrophilicity, and thus accessible water concentration, caused by ring-opening of the dimethyl-γ-butyrolactone.

The objective of this work is to create an in situ physically and chemically cross-linking hydrogel for in vivo applications. N-isopropylacrylamide (NIPAAm) was copolymerized with N-acryloxysuccinimide (NASI) via free radical polymerization. Poly(NIPAAm-co-NASI) was further modified to obtain Poly(NIPAAm-co-cysteamine) through a nucleophilic attack on the carbonyl group of the NASI by the amine group of the cysteamine. Modification was verified by nuclear magnetic resonance. In addition to thermo-responsive physical gelling due to the presence of NIPAAm, this system also chemically gels via a Michael-Type addition reaction when mixed with poly(ethylene glycol) diacrylate (PEGDA). The presence of both physical and chemical gelation resulted in material properties that are much improved compared to purely physical gels. The chemical gelation time of the copolymers was not significantly affected by the amount of thiol present due to the increased pKa of the copolymer containing more thiols. In addition, the swelling of the copolymers was highly dependent on temperature and thiol content. Lastly, the rate of nucleophilic attack in the Michael-Type addition reaction was shown to be highly dependent on pH and on the mole ratio of thiol to acrylate. Due to the improved mechanical properties, this material may be better suited for long-term functional replacement applications than other thermo-sensitive physical gels. With further development and biocompatibility testing, this material could potentially be applied as a temperature-responsive injectable biomaterial for functional embolization.