Physical stimuli-responsive DNA hydrogels: design, fabrication strategies, and biomedical applications

Physical stimuli-responsive DNA hydrogels hold immense potential for tissue engineering due to their inherent biocompatibility, tunable properties, and capacity to replicate the mechanical environment of natural tissue, making physical stimuli-responsive DNA hydrogels a promising candidate for tissue engineering. These hydrogels can be tailored to respond to specific physical triggers such as temperature, light, magnetic fields, ultrasound, mechanical force, and electrical stimuli, allowing precise control over their behavior. By mimicking the extracellular matrix (ECM), DNA hydrogels provide structural support, biomechanical cues, and cell signaling essential for tissue regeneration. This article explores various physical stimuli and their incorporation into DNA hydrogels, including DNA self-assembly and hybrid DNA hydrogel methods. The aim is to demonstrate how DNA hydrogels, in conjunction with other biomolecules and the ECM environment, generate dynamic scaffolds that respond to physical stimuli to facilitate tissue regeneration. We investigate the most recent developments in cancer therapies, including injectable DNA hydrogel for bone regeneration, personalized scaffolds, and dynamic culture models for drug discovery. The study concludes by delineating the remaining obstacles and potential future orientations in the optimization of DNA hydrogel design for the regeneration and reconstruction of tissue. It also addresses strategies for surmounting current challenges and incorporating more sophisticated technologies, thereby facilitating the clinical translation of these innovative hydrogels.