Wang Zihao, Zhou Mengxue, Li Mengyu, Li Jinyu, Zhang Shengmin, Wang Jianglin
Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China.
NMPA Research Base of Regulatory Science for Medical Devices, Institute of Regulatory Science for Medical Devices, Huazhong University of Science and Technology, Wuhan, 430074, China.
Bioact Mater. 2024 Jul 17;41:127-136. doi: 10.1016/j.bioactmat.2024.07.006. eCollection 2024 Nov.
Current gold standard for the replacement of small-diameter blood vessel (ID < 4 mm) is still to utilize the autologous vessels of patients due to the limitations of small-diameter vascular grafts (SDVG) on weak endothelialization, intimal hyperplasia and low patency. Herein, we create the SDVG with the tailored endothelialization by applying the engineered endothelial cell vesicles to camouflaging vascular grafts for the enhancement of vascular remodeling. The engineered endothelial cell vesicles were modified with azide groups (ECVs-N) through metabolic glycoengineering to precisely link the vascular graft made of PCL-DBCO via click chemistry, and thus fabricating ECVG (ECVs-N modified SDVG), which assists inhibition of platelet adhesion and activation, promotion of ECs adhesion and enhancement of anti-inflammation. Furthermore, single-cell transcriptome analysis revealed that the proportion of ECs in the cell composition of ECVG surpassed that of PCL, and the tailored endothelialization enabled to convert endothelial cells (ECs) into some specific ECs clusters. One of the specific cluster, Endo_C5 cluster, was only detected in ECVG. Consequently, our study integrates the engineered membrane vesicles of ECVs-N from native ECs for tailored endothelialization on SDVG by circumventing the limitations of living cells, and paves a new way to construct the alternative endothelialization in vessel remodeling following injury.
由于小口径血管移植物（SDVG）在内皮化薄弱、内膜增生和通畅率低方面存在局限性，目前用于替换小口径血管（内径<4mm）的金标准仍是利用患者自身血管。在此，我们通过应用工程化内皮细胞囊泡伪装血管移植物以增强血管重塑，从而创建具有定制内皮化的SDVG。通过代谢糖工程用叠氮基团（ECVs-N）修饰工程化内皮细胞囊泡，通过点击化学精确连接由PCL-DBCO制成的血管移植物，从而制造出ECVG（ECVs-N修饰的SDVG），其有助于抑制血小板粘附和激活、促进内皮细胞粘附并增强抗炎作用。此外，单细胞转录组分析显示，ECVG细胞组成中内皮细胞的比例超过了PCL，定制的内皮化能够将内皮细胞（ECs）转化为一些特定的ECs簇。其中一个特定簇，即Endo_C5簇，仅在ECVG中检测到。因此，我们的研究通过规避活细胞的局限性，整合了来自天然内皮细胞的工程化膜囊泡ECVs-N用于SDVG的定制内皮化，并为损伤后血管重塑中构建替代性内皮化开辟了一条新途径。
