Applications of DNA Hydrogels in Osteoporotic Bone Defects.

DNA hydrogels are an emerging class of biomaterials with programmability, biodegradability, biocompatibility, and dynamic responsiveness, enabling precise regulation of osteoblast and mesenchymal stem cell (MSC) proliferation and differentiation, activation of key signaling pathways, and promotion of angiogenesis and bone matrix mineralization. In contrast, conventional bone repair materials exhibit limitations including poor mechanical strength, uncontrollable degradation, and inadequate matching with native bone properties, restricting their application in osteoporotic defect repair. Current osteoporotic defect therapies, mainly anti-resorptive and anabolic agents, remain insufficient for many patients. Here, we propose pure and hybrid DNA hydrogels as novel therapeutic platforms to restore the dynamic balance between bone resorption and formation, thereby enhancing osteogenesis and facilitating bone regeneration and remodeling under osteoporotic conditions. Although challenges such as high production cost and long-term safety persist, integration with advanced technologies (e.g., 3D printing and gene editing) may provide theoretical support for further investigation of personalized and intelligent therapeutic strategies at the pre-clinical research stage, offering new insights into osteoporotic bone defects and bone tissue regeneration.