Tailoring the degradation rates of thermally responsive hydrogels designed for soft tissue injection by varying the autocatalytic potential

Abstract

The ability to modulate the degradation properties of biomaterials such as thermally responsive hydrogels is desirable when exploring new therapeutic strategies that rely on the temporary presence of a placed scaffold or gel. Here we report a method of manipulating the absorption rate of a poly(N-isopropylacrylamide) ((poly(NIPAAm)) based hydrogel across a wide range (from 1 d to 5 mo) by small alterations in the composition. Relying upon the autocatalytic effect, the degradation of poly(NIPAAm-co-HEMA-co-MAPLA), (HEMA = 2-hydroxyethyl methacrylate; MAPLA = methacrylate-polylactide) was greatly accelerated by adding a fourth monomer methacrylic acid (MAA) at no more than 2 mol% to obtain poly(NIPAAm-co-HEMA-co-MAPLA-co-MAA) (pNHMMj) where j reflects the MAA molar % in the reactant mixture. MAA residue introduction decreased the pH inside the hydrogels and in surrounding buffered solutions. Accelerated degradation positively correlated with MAA content in pNHMMj polymers, putatively by the accelerated cleavage of MAPLA residues to raise the transition temperature of the polymer above body temperature. Physical properties including thermal transition behavior and initial mechanical strength did not vary significantly with MAA content. A rat hindlimb injection model generally reflected the in vitro observation that higher MAA content resulted in more rapid degradation and cellular infiltration. The strategy of tuning the degradation of thermally responsive hydrogels where degradation or solubilization is determined by their polyester components might be applied to other tissue engineering and regenerative medicine applications where designed biomaterial degradation behavior is needed.