Tang Like, Wang Yuchen, Mao Shihua, Yu Zhou, Chen Yitong, Xu Xiaoqiao, Cai Wenjin, Lai Kaichen, Yang Guoli, Huang Tingben
Stomatology Hospital, School of Stomatology, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Zhejiang University School of Medicine, Cancer Center of Zhejiang University, Hangzhou, 310000, China.
The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
J Nanobiotechnology. 2025 May 14;23(1):348. doi: 10.1186/s12951-025-03431-w.
Heterotopic Ossification (HO), refers to pathological extra skeletal bone formation, and there are currently no reliable methods except surgery to reverse these unexpected calcified tissues. Apoptotic vesicles (ApoEVs) are membrane-bound vesicles released by apoptotic cells, which are involved in metabolism regulation and intercellular communication. Due to its superior trauma-healing ability, the hard palate mucosa is expected to become an essential resource for tissue engineering. This work presents a minimally invasive nanotherapy based on an engineered apoEV. Briefly, apoEVs were extracted from hard palate mucosa and engineered with bone-targeting peptide SDSSD to treat HO. This engineered apoEV not only can achieve directed localization of heterotopic bones but also has the compelling dual function of promoting osteoclastic differentiation while inhibiting osteogenic differentiation. The underlying mechanism involves the activation of Hippo and Notch pathways, as well as the regulation of pyrimidine metabolism. We envision that this engineered apoEV may be a feasible and effective strategy for reversing HO.
异位骨化（HO）是指骨骼外的病理性骨形成，目前除了手术外，没有可靠的方法来逆转这些意外形成的钙化组织。凋亡小泡（ApoEVs）是凋亡细胞释放的膜结合小泡，参与代谢调节和细胞间通讯。由于其卓越的创伤愈合能力，硬腭黏膜有望成为组织工程的重要资源。这项工作提出了一种基于工程化ApoEV的微创纳米疗法。简而言之，从硬腭黏膜中提取ApoEV，并使用骨靶向肽SDSSD对其进行工程改造以治疗HO。这种工程化的ApoEV不仅可以实现异位骨的定向定位，还具有促进破骨细胞分化同时抑制成骨细胞分化的双重功能。其潜在机制涉及Hippo和Notch信号通路的激活以及嘧啶代谢的调节。我们设想这种工程化的ApoEV可能是逆转HO的一种可行且有效的策略。
