Biodegradable DNA-enabled poly(ethylene glycol) hydrogels prepared by copper-free click chemistry

Abstract

Significant research has focused on investigating the potential of hydrogels in various applications and, in particular, in medicine. Specifically, hydrogels that are biodegradable lend promise to many therapeutic and biosensing applications. Endonucleases are critical for mechanisms of DNA repair. However, they are also known to be overexpressed in cancer and to be present in wounds with bacterial contamination. In this work, we set out to demonstrate the preparation of DNA-enabled hydrogels that could be degraded by nucleases. Specifically, hydrogels were prepared through the reaction of dibenzocyclooctyne-functionalized multi-arm poly(ethylene glycol) with azide-functionalized single-stranded DNA in aqueous solutions via copper-free click chemistry. Through the use of this method, biodegradable hydrogels were formed at room temperature in buffered saline solutions that mimic physiological conditions, avoiding possible harmful effects associated with other polymerization techniques that can be detrimental to cells or other bioactive molecules. The degradation of these DNA-cross-linked hydrogels upon exposure to the model endonucleases Benzonase^® and DNase I was studied. In addition, the ability of the hydrogels to act as depots for encapsulation and nuclease-controlled release of a model protein was demonstrated. This model has the potential to be tailored and expanded upon for use in a variety of applications where mild hydrogel preparation techniques and controlled material degradation are necessary including in drug delivery and wound healing systems.

Keywords:

• Biodegradation
• click chemistry
• hydrogel
• DNA
• nuclease-mediated degradation
• stimuli-responsive biomaterials
• protein release

Disclosure statement

No potential conflict of interest was reported by the authors.

Acknowledgements

This work was supported in part by the National Science Foundation Partnership in Research and Education in Materials (PREM) (DMR-1205670), the Research Corporation for Science Advancement, the Texas Emerging Technology Fund, The Welch Foundation (AI-0045), and the Texas State University Thesis Research Support Fellowship (to KB).