Injectable hydrogels based on poly(ethylene glycol) and derivatives as functional biomaterials

Abstract

The design criteria for injectable, in situ-gelling hydrogels are reviewed in conjunction with highlights on recent progress in the preparation of injectable PEG and PEG-analogue poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels.

Controlling the Release of Small, Bioactive Proteins via Dual Mechanisms with Therapeutic Potential

“…[5, 10] The release of cargo from PEG-based hydrogels generally is controlled by Fickian diffusion (e.g., encapsulation of protein and release by passive or hindered diffusion), material degradation (e.g., entrapment of protein and release upon crosslink cleavage), or a combination of both. The incorporation of natural polymers (e.g., polysaccharides such as heparin) within hydrogels allows for non-covalent interactions with biological cargo, which both improve the stability of cargo molecules during the encapsulation process and the control of cargo release kinetics.…”

Enhanced Mechanical Properties in Cellulose Nanocrystal–Poly(oligoethylene glycol methacrylate) Injectable Nanocomposite Hydrogels through Control of Physical and Chemical Cross-Linking

“…Previously, both CNCs 32,35 and POEGMA hydrogels 8,24 have been shown in various studies to be non-cytotoxic. Here, we show that POEGMA-CNC nanocomposite hydrogels are also non-cytotoxic, with CNC loading having no significant impact on cell viability.…”

“…8,20,21 Unlike poly(ethylene glycol) (PEG), which can only be end-group functionalized, the free radical (co)polymerization method used to produce POEGMA enables the incorporation of a range of reactive comonomers or cross-linkers, facilitating production of pre-gel precursor polymers with a range of desired chemistries, cross-link densities, and molecular weights. We have previously reported extensively on modular POEGMA hydrogels cross-linked via hydrazone bonds, formed by reactive extrusion of aldehyde and hydrazide-functionalized precursor polymers.…”

“…methods have been applied to create hydrogels, recent advances in in situ-gelling chemistries (including largely bio-orthogonal click chemistry-based approaches 6,[8][9][10] ) have made hydrogels particularly translatable to biomedical applications, eliminating the need for gelation initiators such as heat, excessive agitation, chemical activators, UV light, or pH changes while enabling minimally invasive delivery to targeted sites in the body. Moreover, these injectable materials can be engineered to display tunable biodegradation under different environmental conditions depending on the chemistry used to form the cross-links.…”

“…We have previously reported extensively on modular POEGMA hydrogels cross-linked via hydrazone bonds, formed by reactive extrusion of aldehyde and hydrazide-functionalized precursor polymers. 8,[22][23][24][25][26] Hydrogel properties including the lower critical solution temperature (LCST), cross-link density, swelling ratio, and cell adhesion can be modified by varying the ethylene oxide side chain length, 24 combining multiple precursor polymers, 22 or introducing hydrophobic domains into the precursor polymers. 26 However, the mechanical strength of these materials remains limited; more specifically, in the context of the highly protein and cell-repellent POEGMA hydrogels based on long oligo(ethylene glycol) side chains, even highly functionalized precursor polymers (30 mol % hydrazide or aldehyde-bearing repeat units) lead to hydrogels with only moderate mechanical strength (~1 kPa shear storage modulus).…”