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.

Functionalized DNA Hydrogels Produced by Polymerase‐Catalyzed Incorporation of Non‐Natural Nucleotides as a Surface Coating for Cell Culture Applications

“…Further analysis by scanning electron microscopy shows that the casting process of the DNA hydrogel using a flat foil‐cover yields a DNA material with a flat surface and minor wrinkles (Figure B I). Analysis of gel cross‐sections (Figure B II) revealed honeycombed structures which form the bulk of the material and show similar morphologies of other hydrogels …”

Achieving Controlled Biomolecule–Biomaterial Conjugation

“… 230 , 234 , 236 , 237 This cytocompatibility of SPAAC reactions is particularly attractive, as is the lack of ROS generation, enabling the efficient functionalization and cross-linking of hydrogels with complementary DNA strands. 238 …”

Functional Hydrogels and Their Application in Drug Delivery, Biosensors, and Tissue Engineering

“…In addition to the five biomedical hydrogels cited above, research has led to the development of a number of other novel hydrogels, including DNAenabled hydrogels, and magnetic hyaluronate hydrogels [98,99]. DNA-enabled hydrogels have been synthesized through the reaction of dibenzocyclooctyne-functionalized multiarm poly(ethylene glycol) with azide-functionalized single-stranded DNA in aqueous solutions by copper-free click chemistry (Figure 4) [98]. Besides, the hydrogel contained with the adipose-derived stem cells has been reported that can augment diabetic wound healing [100].…”