Tuning the properties of in situ gelling POEGMA hydrogels by controlling precursor polymer molecular weight and structure

Abstract

Injectable hydrogels made from synthetic polymers represent a versatile class of biomaterials that have been extensively investigated for their potential application as drug delivery vehicles and tissue engineering scaffolds, due to their ease of in vivo delivery, high tuneability, and across-linked hydrophilic network structure that has mechanical and chemical similarities to native tissues. In the case of injectable hydrogels that are formed via covalent bonds between synthetic polymers, hydrogel properties can often be tuned by chemical modification of the precursor polymers. However, changing the chemistry of a hydrogel system can often have unforeseen or unintended consequences in terms of factors such as drug partitioning or how cells interact with the hydrogel substrate. There is a need, therefore, for devising alternative methods to modulate the properties of hydrogels while maintaining chemical uniformity within the gels. This thesis investigates two methods for modulating the properties of poly(oligoethylene glycol methacrylate) (POEGMA) based injectable hydrogels that work by changing the structural characteristics of the POEGMA precursors while maintaining uniformity of chemical factors such as functional group distribution. POEGMA is a widely used synthetic poly(ethylene glycol) analogue that has a number of beneficial properties including being biodegradable, non-cytotoxic, and readily functionalizable. In the first method, the properties of POEGMA-based hydrogels were modulated by changing the molecular weight of the POEGMA precursors that were used to form the gels. Well-defined functionalized POEGMA polymers of various molecular weights (with complementary hydrazide/aldehyde functionalities) were prepared using RAFT polymerization, and the polymers were subsequently mixed to form hydrogels in situ via rapid formation of hydrazine bonds. These gels were assessed to determine how polymer molecular weight affects properties such as mechanical strength, swelling/degradation, and gelation kinetics. In the second method, hyperbranched POEGMA polymers were prepared by inclusion of a di-vinyl cross-linker into the RAFT polymerization of these polymers. A series of functionalized polymers was prepared by varying the degree of branching in the polymers, with the properties of these polymers subsequently investigated to determine how branching degree affected polymer properties. The polymers were then demonstrated to be capable of forming hydrogels in situ. Overall, by applying chemistry-driven approaches to engineer defined structures in the precursor components of hydrogels, gels with well-defined and tunable properties that are directly related to the structure of those precursor polymers can be achieved, permitting the preparation of injectable hydrogels with highly analogous chemistries but different bulk properties.