Ji Xiuru, Zhou Jingwei, Zhou Zengding, Liu Zeyang, Yan Li, Li Yuhan, Guo Haiyan, Su Weijie, Wang Han, Ni Dalong
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Rd, Shanghai, 200025, PR China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Rd, Shanghai, 200011, PR China.
Bioact Mater. 2024 Aug 29;42:112-123. doi: 10.1016/j.bioactmat.2024.08.024. eCollection 2024 Dec.
Skin-nerve interaction plays an important role in promoting wound healing. However, in diabetic ulcers (DUs), the diabetic periphery neuropathy and excessive levels of reactive oxygen species (ROS) block skin-nerve interaction and further impede the DUs healing. Herein, we developed a nanoscale metal-organic framework loaded with nerve growth factor (NGF/Ce-UiO-66, denoted NGF/CU) for the treatment of DUs. The Ce-UiO-66 (CU) was applied as an antioxidant to scavenge ROS and reduce the inflammatory response while the NGF aided in the recovery of cutaneous nerves to further promote DUs healing. Both and experiments revealed the effective ability of NGF/CU for DUs healing. Subsequent RNA sequencing analysis revealed the mechanism that NGF/CU can improve wound healing by inhibiting the NF-κB signaling pathway and recovering the neuroendocrine system of the skin. This strategy of nerve regulation will provide more ideas for the treatment of DUs and other organ injuries.
皮肤-神经相互作用在促进伤口愈合中起着重要作用。然而，在糖尿病溃疡（DU）中，糖尿病周围神经病变和活性氧（ROS）水平过高会阻碍皮肤-神经相互作用，进一步妨碍糖尿病溃疡的愈合。在此，我们开发了一种负载神经生长因子的纳米级金属有机框架（NGF/Ce-UiO-66，简称NGF/CU）用于治疗糖尿病溃疡。Ce-UiO-66（CU）作为抗氧化剂来清除ROS并减轻炎症反应，而NGF有助于皮肤神经的恢复以进一步促进糖尿病溃疡的愈合。体内和体外实验均揭示了NGF/CU促进糖尿病溃疡愈合的有效能力。随后的RNA测序分析揭示了NGF/CU可通过抑制NF-κB信号通路和恢复皮肤神经内分泌系统来改善伤口愈合的机制。这种神经调节策略将为糖尿病溃疡和其他器官损伤的治疗提供更多思路。
