Manipulating Degradation Time in a N-isopropylacrylamide-Based Co-polymer with Hydrolysis-Dependent LCST

Abstract

A thermosensitive, bioresorbable and in situ gelling co-polymer, poly(N-isopropylacrylamide-co-dimethyl-gamma-butyrolactone acrylate-co-acrylic acid), was synthesized by radical co-polymerization with varying dimethyl-gamma-butyrolactone acrylate (DBA) content. The materials properties were characterized using differential scanning calorimetry, gel-permeation chromatography in conjunction with static light scattering, Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) and acid titration. The initial lower critical solution temperature (LCST) of the synthesized co-polymer is between room temperature and body temperature. With the increase of DBA content, the LCST decreases, but then increases after the ring-opening hydrolysis of the DBA side-group. The FT-IR and NMR spectra show the co-polymerization of three monomers, as well as the hydrolysis-dependent ring-opening of the DBA side-group. The addition of acrylic acid increases the initial LCST and accelerates the degradation rate of the co-polymer. An indirect cytotoxicity test indicated that this co-polymer has relatively low cytotoxicity as seen with 3T3 fibroblast cells.

In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering

“…This suggests that modulating the hydrophobicity of the hydrogel through the timescale of DBA hydrolysis would improve the performance of the TGM/DBA groups in future studies in this defect model. Studies by other groups have previously established that hydrolysis sufficient enough to drive the LCST of a DBA-containing thermogelling hydrogel above body temperature (enabling for hydrogel degradation) occurred on the order of days depending on the DBA content, incorporation of AA, and environmental conditions [41]. However, in the dual gelling system, the DBA hydrolysis occurs within minutes, due to greater hydrogel stabilization and higher swelling from the additional chemical crosslinking [23].…”

Synthesis, Physicochemical Characterization, and Cytocompatibility of Bioresorbable, Dual-Gelling Injectable Hydrogels

“…In these cases involving polyesters, lactate side chains, or poly(amino acids), the monomers also produced soluble degradation products that may be toxic to encapsulated cells and raise the pH of the local microenvironment. In a different study, Cui et al achieved PNiPAAm biodegradation without toxic byproducts through incorporation of dimethyl-γ-butyrolactone acrylate (DBA), a hydrolyzable lactone ring 19, 20 . Hydrolysis of the ester group in the ring structure resulted in the formation of hydroxyl and carboxyl groups, which increased the hydrophilicity, and subsequently, the LCST of the polymer.…”

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

“…For thermally responsive systems that employ crosslinking, adjusting the crosslinking density is effective [25]. In poly(N-isopropylacrylamide) based hydrogels, the content of hydrolytic pendant groups has been shown to have a significant influence on both hydrogel degradation rate and thermal transition behaviors [26]. In other cases, introducing enzyme sensitive cleavage sites has proven an effective mechanism [27–29].…”