FUNCTIONALIZING DNA-BASED HYDROGELS WITH DNA ORIGAMI FOR THE DEVELOPMENT OF “SMART” SCAFFOLDS FOR TISSUE ENGINEERING

Hydrogel-based biomaterials have emerged as a promising tool for various biomedical applications due to their biocompatibility, high water content, compositional versatility, and three-dimensional porous structure that mimic the structure of their native counterparts. Their applications span from wound healing and tissue engineering to drug delivery systems, largely due to their tunable physical and chemical properties. DNA-based hydrogels are a novel class of synthetic hydrogels that offer additional advantages such as self-assembling/healing capabilities, finely tunable mechanical properties, and precise conjugation of biomolecules. These novel hydrogels have the potential to replace traditional hydrogels used in regenerative medicine. However, current DNA-based hydrogels often sacrifice structural and mechanical integrity for controlled biomolecule release, which is suboptimal in wound healing applications where maintaining mechanical stability is essential for supporting tissue regeneration. This research aims to address this limitation by developing a novel type of DNA hydrogel functionalized with DNA origami via a stimulus-responsive linker, designed to enhance multiplexed delivery of biomolecules while preserving structural integrity to support cellular adhesion and tissue repair. The hydrogel will function as a “smart” scaffold, selectively releasing DNA origami (that can be loaded with bioactive molecules such as growth factors, anti-inflammatory or anti-microbial agents, etc.) in response to specific environmental cues as in native tissues. The primary focus is on a photocleavable release mechanism that allows precise cleavage control via UV light activation. Additionally, an alternative release mechanism utilizing matrix metalloproteinases (MMP)-sensitive linkers is explored, enabling enzyme-triggered drug deployment in response to the biochemical signals of tissue remodeling. By designing such a platform technology, this self-responsive system could be integrated into wound dressings or implantable devices, where a therapeutic effect can be triggered by a particular facet of the wound microenvironment (enzymes, pH, bacteria, etc.) while preserving the DNA hydrogel’s structure and function.