Synthesis and Spatiotemporal Modification of Biocompatible and Stimuli-Responsive Carboxymethyl Cellulose Hydrogels Using Thiol-Norbornene Chemistry

Abstract

Carboxymethyl cellulose (CMC) is functionalized with norbornene groups to undergo thiol-norbornene cross-linking reactions. Hydrogels synthesized from a single norbornene-modified carboxymethyl cellulose (NorCMC) via a light-initiated thiol-ene cross-linking reaction with a variety of dithiol cross-linkers yield hydrogels with a tunable compression modulus ranging from 1.7 to 103 kPa. Additionally, thermoresponsiveness is spatiotemporally imparted to NorCMC hydrogels by photopatterning a dithiol-terminated poly(N-isopropyl acrylamide) cross-linker, enabling swelling and topological control of the hydrogels as a function of incubation temperature. NorCMC hydrogels are cytocompatible as the viability of encapsulated human mesenchymal stem cells (hMSCs) is greater than 85% after 21 d while using a variety of cross-linkers. Moreover, hMSCs can remodel, adhere, and spread in the NorCMC matrix cross-linked with a matrix metalloproteinase-degradable peptide, further demonstrating the utility of these materials as a tunable biomaterial.

Keywords: carboxymethyl cellulose; photopatterning; spatiotemporal modification; stimuli-responsive; thiol-ene reaction.