Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China.
ACS Appl Mater Interfaces. 2022 Aug 3;14(30):34427-34442. doi: 10.1021/acsami.2c08491. Epub 2022 Jul 22.
Fracture nonunion can result in considerable physical harm and limitation of quality of life in patients, exerting an extensive economic burden to the society. Nonunion largely results from unresolved inflammation and impaired osteogenesis. Despite advancements in surgical techniques, the indispensable treatment for nonunion is robust anti-inflammation therapy and the promotion of osteogenic differentiation. Herein, we report that plasma exosomes derived from infected fracture nonunion patients (Non-Exos) delayed fracture repair in mice by inhibiting the osteogenic differentiation of bone marrow stromal cells in vivo and in vitro. Unique molecular identifier microRNA-sequencing (UID miRNA-seq) suggested that microRNA-708-5p (miR-708-5p) was overexpressed in Non-Exos. Mechanistically, miR-708-5p targeted structure-specific recognition protein 1, thereby suppressing the Wnt/β-catenin signaling pathway, which, in turn, impaired osteogenic differentiation. AntagomicroRNA-708-5p (antagomiR-708-5p) could partly reverse the above process. A bacteria-sensitive natural polymer hyaluronic-acid-based hydrogel (HA hydrogel) loaded with antagomiR-708-5p exhibited promising effects in an in vivo study through antibacterial and pro-osteogenic differentiation functions in infected fractures. Overall, the effectiveness and reliability of an injectable bacteria-sensitive hydrogel with sustained release of agents represent a promising approach for infected fractures.
骨折不愈合会给患者带来相当大的身体伤害和生活质量受限，并给社会带来广泛的经济负担。不愈合主要是由于炎症未得到解决和成骨受损所致。尽管手术技术有所进步，但不愈合的必要治疗方法是强有力的抗炎治疗和促进成骨分化。在这里，我们报告称，来自感染性骨折不愈合患者的血浆外泌体（Non-Exos）通过体内和体外抑制骨髓基质细胞的成骨分化，延迟了小鼠的骨折修复。独特分子标识符 microRNA 测序（UID miRNA-seq）表明，Non-Exos 中 miR-708-5p（miR-708-5p）表达过度。在机制上，miR-708-5p 靶向结构特异性识别蛋白 1，从而抑制 Wnt/β-catenin 信号通路，进而损害成骨分化。抗 microRNA-708-5p（antagomiR-708-5p）可部分逆转上述过程。负载 antagomiR-708-5p 的细菌敏感天然聚合物透明质酸水凝胶（HA 水凝胶）在体内研究中通过抗菌和促进成骨分化功能，在感染性骨折中表现出良好的效果。总体而言，具有持续释放药物的可注射细菌敏感水凝胶的有效性和可靠性代表了一种有前途的感染性骨折治疗方法。
