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Significance Statement
Hydrogels are of particular interest for a number of medical applications such as tissue engineering and drug delivery. This is owing to their highly hydrated tissue-like environment, superior biocompatibility, and excellent mechanical and physical attributes. Most of these applications demand hydrogels that can degrade under physiological attributes in a predetermined period. Previous work has indicated that by precisely controlling the polymeric chain network chemical structure and physical properties, degradation can be implemented to temporally tune drug release and to regulate cell growth and differentiation.
Several polymers as well as chemistries can be implemented to produce degradable hydrogels and tune their mechanical, biochemical, and degradation properties. Suitable selection of the macromolecular hydrogel precursors allows for tailor-made initial hydrogel attributes as well as the hydrogel degradation attributes to match a preferred application.
Polyethylene glycol is majorly studied for designing degradable hydrogels owing to its bio-inertness, excellent versatility, and biocompatibility. Unfortunately, polyethylene glycol lacks reactive functional groups, and hydrolytic and enzymatic degradation sites. Thus, end-functionalized polyethylene glycol derivatives with thiol, malemide, acrylate, and vinyl sulfone have been developed to allow for the formation of insoluble polyethylene glycol networks. These hydrogel networks can be further rendered degradable in physiologically relevant environments by the incorporation of various hydrolytically or enzymatically degradable sites, such as ester moieties or peptide-based crosslinkers.
Dr. Era Jain and colleagues at Saint Louis University investigated hydrolytically degradable polyethylene glycol hydrogels, and the function of the chemical structure as well as physical attributes of thiol-functionalized crosslinkers on polyethylene glycol hydrogel gelation and degradation. The main motivation of their research was that by selecting α, β, or γ-substituents of the thiol or ester moiety of the crosslinker, one could tune degradation or gelation of the resulting hydrogel. Their work is published in Journal of Materials Chemistry B.
The authors analyzed the relationship between the dithiol crosslinker chemical and physical structure and the resultant attributes of polyethylene glycol hydrogels produced through Michael-type addition reaction. Precisely, the authors correlated the dithiol crosslinker characteristics and chemical structure with gelation time, reaction rate constant, hydrolytic degradation rate, crosslink density, and storage modulus of polyethylene glycol hydrogels.
Through a vigilant selection of the dithiol crosslinker structure as well as physical attributes, the authors were able to generate an array of degradable hydrogels of different gelation, degradation rates and preceding hydrogel attributes. They realized that the hydrogel degradation times were related to gelation times, which indicated that degradation and hydrogel formation were dictated by the same attributes of the chemical structure of the dithiol crosslinkers.
The research team observed that dithiol crosslinkers with pKa<9 exhibited faster gelation and degradation times, while crosslinkers with pKa>9 had slower gelation and degradation times. In addition, they were able to tune the hydrogel modulus independent of degradation times. This was possible by choosing crosslinkers with varying physical properties.
This detailed evaluation of dithiol crosslinkers presented in the study can enable the design of dithiol crosslinkers, which can be implemented to realize hydrogels with tuned degradation rates, moduli, and swelling. This would also guide their implementation for numerous biomedical applications.
Reference
Era Jain, Lindsay Hill, Erin Canning, Scott A. Sell and Silviya P. Zustiak. Control of gelation, degradation and physical properties of polyethylene glycol hydrogels through the chemical and physical identity of the crosslinker. J. Mater. Chem. B, 2017, 5, 2679–2691
Go To Journal of Materials Chemistry B