Shi Ruijianghan, Zhan Huilu, Jiang Shan, Lin Kaili, Yuan Changyong
Department of Oral and Craniomaxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200125, China.
Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Adv Sci (Weinh). 2025 Oct;12(39):e11099. doi: 10.1002/advs.202511099. Epub 2025 Sep 8.
Musculoskeletal disorders, including bone fractures, osteoarthritis, and muscle injuries, represent a leading cause of global disability, revealing the urgency for advanced therapeutic solutions. However, current therapies face limitations including donor-site morbidity, immune rejection, and inadequate mimicry of dynamic tissue repair processes. DNA-based hydrogels emerge as transformative platforms for musculoskeletal reconstruction, with their sequence programmability, dynamic adaptability, and biocompatibility to balance structural support and biological functions. These hydrogels are classified into two categories: 1) DNA hydrogels, where DNA serves as the structural backbone; 2) DNA component-loaded hydrogels, integrating functional DNA elements like aptamers and therapeutic genes into non-DNA matrices. Through dynamic crosslinking strategies, primarily Watson-Crick base pairing, DNA networks achieve shear-thinning injectability and self-healing behaviors while providing binding sites for bioactive DNA components. Hybrid systems further enhance functionality by incorporating diverse materials to improve mechanical strength, drug delivery, and cellular guidance. This review systematically examines molecular design principles, classification frameworks, and preclinical applications of DNA-based hydrogels, aiming to bridge gaps between material innovation and clinical translation. Finally, current challenges are highlighted, and future directions to advance these intelligent biomaterials toward next-generation musculoskeletal therapies are proposed.
肌肉骨骼疾病，包括骨折、骨关节炎和肌肉损伤，是全球残疾的主要原因之一，这凸显了先进治疗方案的紧迫性。然而，目前的治疗方法存在局限性，包括供体部位发病、免疫排斥以及对动态组织修复过程的模拟不足。基于DNA的水凝胶作为肌肉骨骼重建的变革性平台出现，其具有序列可编程性、动态适应性和生物相容性，能够平衡结构支撑和生物学功能。这些水凝胶分为两类：1）DNA水凝胶，其中DNA作为结构骨架；2）负载DNA成分的水凝胶，将适体和治疗基因等功能性DNA元件整合到非DNA基质中。通过动态交联策略，主要是沃森-克里克碱基配对，DNA网络实现了剪切变稀的可注射性和自愈行为，同时为生物活性DNA成分提供结合位点。混合系统通过结合多种材料进一步增强功能，以提高机械强度、药物递送和细胞引导能力。本综述系统地研究了基于DNA的水凝胶的分子设计原则、分类框架和临床前应用，旨在弥合材料创新与临床转化之间的差距。最后，强调了当前面临的挑战，并提出了将这些智能生物材料推进到下一代肌肉骨骼治疗的未来方向。
