Design and Synthesis of Hybrid Thermo-Responsive Hydrogels Based on Poly(2-oxazoline) and Gelatin Derivatives

The combination of natural and synthetic polymers to form hybrid hydrogels offers the potential of fabricating new materials that possess a combination of properties resulting from both types of polymer classes. Within this work, two alkene-functionalized poly(2-alkyl/aryl–2-oxazoline) (PAOx) copolymers and one gelatin derivative, thiolated gelatin (gel-SH), are synthesized as precursors for hybrid hydrogels through a photo-induced radical thiol-ene crosslinking process. In-situ photo-rheology revealed an increased mechanical stability for hydrogels that possess an excess amount of PAOx precursor. A final qualitative investigation of the thermo-responsive properties of a P(EtOx(270)–norbornenOx(30)):gel-SH (2:1) hydrogel film revealed a cloud point temperature (T(cp)) in the same range as the T(cp) of the P(EtOx(270)–norbornenOx(30)) polymer precursor, which is around 30 °C. This promising result demonstrates that thermo-responsive hybrid poly(2-oxazoline)-gelatin hydrogels could be prepared with predictable T(cp)s and that further investigation into this appealing feature might be of interest. Ultimately, this work shows a proof-of-concept of using PAOx as potential hybrid hydrogel precursor in combination with cell-interactive gelatin derivatives to potentially improve the mechanical stability of the final scaffolds and introduce additional features such as thermo-responsiveness for the purpose of drug delivery.