Bioengineering DNA-based hydrogels for regenerative medicine: A review of programmable design, chemical synthesis and therapeutic potential.

DNA hydrogels have emerged as a transformative class of intelligent biomaterials for regenerative medicine, leveraging the unique programmability, precise molecular recognition, and excellent biocompatibility. Although substantial progress has been made in the development of DNA hydrogels for biomedical applications, a comprehensive understanding about how construction strategies govern physicochemical properties, biological functions, and regenerative medicine remains fragmented. This review systematically examines the molecular design principles, construction strategies, and advanced functionalities of DNA hydrogels, with a focus on their translation into tissue engineering and clinical applications. Physicochemical and biological properties are discussed to underpin their performance. The diverse biomedical applications are further highlighted, particularly for their regenerative potential in repairing bone, cartilage, cardiovascular, skin, and neural tissues. Additionally, they play a crucial role in tumor therapy and the regeneration of tumor-resected tissues. This review may provide a rational framework to guide the development of DNA hydrogels toward precisely regenerative medicine and personalized therapies.