Bioorthogonally cross-linked hydrogel network with precisely controlled disintegration time over a broad range

UMMS Affiliation

Department of Orthopedics and Physical Rehabilitation

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology


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.

DOI of Published Version



J Am Chem Soc. 2014 Mar 19;136(11):4105-8. doi: 10.1021/ja4130862. Epub 2014 Mar 5. Link to article on publisher's site

Journal/Book/Conference Title

Journal of the American Chemical Society

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Link to Article in PubMed

PubMed ID