DNA Supramolecular Hydrogel Alters Exosomal microRNA Atlas and Paracrine Secretory Profile of MSCs to Promote Bone Remodeling and Ameliorate Osteoradionecrosis of the Jaw
Abstract
ABSTRACT Osteoradionecrosis of the jaw (ORNJ) is a severe complication of head and neck radiotherapy, characterized by a hostile tissue microenvironment that hinders healing. To address the limitations of mesenchymal stem cell (MSC) therapy, such as rapid dispersion and clearance, we developed an injectable, shear‐thinning DNA supramolecular hydrogel (DNASH) as a 3D scaffold. The DNASH matrix significantly prolonged the local retention of MSCs and their exosomes for over 3 weeks. Crucially, the scaffold actively reprogrammed the MSC secretome by modulating the FAK‑Integrin and Hippo‑YAP mechanotransduction pathways. This directed a shift toward a pro‐regenerative exosomal miRNA profile, notably enriching miR‑146a‑5p and reducing miR‑125b‑5p. In a murine ORNJ model, this MSC‐laden hydrogel orchestrated a coupled bone‐remodeling process, effectively clearing necrotic bone while stimulating robust osteogenesis. The treatment restored mandibular architecture, reduced systemic inflammation, and improved tissue homeostasis, presenting a clinically promising strategy for ORNJ repair.
Article Details
Authors (14)
Yue Li
Xue Li
Miaomiao Qiu
Zhaowei Zhang
Lianqiang Dong
CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry Chinese Academy of Sciences Beijing P. R. China
Zhengyang Wei
Beijing Institute of Radiation Medicine Beijing P. R. China
Lingwei Meng
Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology NMPA Key Laboratory For Dental Materials Beijing P. R. China
Yuanjing Zheng
Beijing Institute of Radiation Medicine Beijing P. R. China
Yang Wang
Yuanlin Liu
Beijing Institute of Radiation Medicine Beijing P. R. China
Dongsheng Liu
Department of Chemistry
Shaoxia Pan
Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology NMPA Key Laboratory For Dental Materials Beijing P. R. China
Yi Zhang
Yuanchen Dong
CAS Key Laboratory of Colloid Interface and Chemical Thermodynamics, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry