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Am. Chem. Soc., 2014, 136(11), pp 4105–4108.
Jianwen Xu , Ellva Feng , Jie Song.
Department of Orthopedics & Physical Rehabilitation, and Department of Cell & Developmental Biology,University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, United States.
Abstract
Hydrogels with predictable degradation are highly desired for biomedical applications where timely disintegration of the hydrogel (e.g., drug delivery, guided tissue regeneration) is required. However, precisely controlling hydrogel degradation over a broad range in a predictable manner is challenging due to limited intrinsic variability in the degradation rate of liable bonds and difficulties in modeling degradation kinetics for complex polymer networks. More often than not, empirical tuning of the degradation profile results in undesired changes in other properties. Here we report a simple but versatile hydrogel platform that allows us to formulate hydrogels with predictable disintegration time from 2 to >250 days yet comparable macroscopic physical properties. This platform is based on a well-defined network formed by two pairs of four-armed polyethylene glycol macromers terminated with azide and dibenzocyclooctyl groups, respectively, via labile or stable linkages. The high-fidelity bioorthogonal reaction between the symmetric hydrophilic macromers enables robust cross-linking in water, phosphate-buffered saline, and cell culture medium to afford tough hydrogels capable of withstanding >90% compressive strain. Strategic placement of labile ester linkages near the cross-linking site within this superhydrophilic network, accomplished by adjustments of the ratio of the macromers used, enables broad tuning of the disintegration rates precisely matching with the theoretical predictions based on first-order linkage cleavage kinetics. This platform can be exploited for applications where a precise degradation rate is targeted.
Copyright © 2014 American Chemical Society
significance statement:
This work reports the predictive design of cytocompatible hydrogels with consistent macroscopic physical properties yet highly tunable degradation profile over a broad range (<2 to >250 days). It combines a perfectly crosslinked, highly swollen homogenous polymer network with the strategic positioning of discrete labile linkages to ensure a degradation behavior closely approximating first-order cleavage kinetics, thereby readily predicted by theoretic modeling. Specifically, high-fidelity, catalyst-free, strain-promoted azide−alkyne cycloaddition (SPAAC) reaction between symmetric hydrophilic macromers is employed to enable robust crosslinking in water, phosphate buffered saline and cell culture medium to afford tough hydrogels capable of withstanding >90% compressive strain. The strategic placement and the facile control over the ratio of labile ester linkages near the SPAAC crosslinking site within the superhydrophilic network enables broad tuning of the hydrogel disintegration rates precisely matching with the theoretical predictions. This platform may be used for advanced biological applications such as drug or stem cell-encapsulating scaffolds for guided tissue regeneration where a combination of adequate mechanical properties, cytocompatible microenvironment and predictive tuning of scaffold disintegration rate (drug release) is desired.
