Departments of Oral and Maxillofacial Surgery, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
State Key Laboratory of Cancer Biology Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Sci Adv. 2022 Jul 15;8(28):eabn1958. doi: 10.1126/sciadv.abn1958. Epub 2022 Jul 13.
Matching material degradation with host remodeling, including endothelialization and muscular remodeling, is important to vascular regeneration. We fabricated 3D PGS-PCL vascular grafts, which presented tunable polymer components, porosity, mechanical strength, and degrading rate. Furthermore, highly porous structures enabled 3D patterning of conjugated heparin-binding peptide, dimeric thymosin β4 (DTβ4), which played key roles in antiplatelets, fibrinogenesis inhibition, and recruiting circulating progenitor cells, thereafter contributed to high patency rate, and unprecedentedly acquired carotid arterial regeneration in rabbit model. Through single-cell RNA sequencing analysis and cell tracing studies, a subset of endothelial progenitor cells, myeloid-derived CD93/CD34 cells, was identified as the main contributor to final endothelium regeneration. To conclude, DTβ4-inspired porous 3DVGs present adjustable physical properties, superior anticoagulating, and re-endothelializing potentials, which leads to the regeneration of small-caliber artery, thus offering a promising tool for vessel replacement in clinical applications.
匹配材料降解与宿主重塑，包括内皮化和肌肉重塑，对于血管再生很重要。我们制备了 3D PGS-PCL 血管移植物，其具有可调的聚合物成分、孔隙率、机械强度和降解率。此外，高度多孔的结构实现了共轭肝素结合肽、二聚体胸腺素 β4（DTβ4）的 3D 图案化，其在抗血小板、纤维蛋白生成抑制和募集循环祖细胞方面发挥关键作用，进而有助于高通畅率，并在兔模型中获得前所未有的颈动脉再生。通过单细胞 RNA 测序分析和细胞示踪研究，确定了一组内皮祖细胞，髓系来源的 CD93/CD34 细胞，是最终内皮再生的主要贡献者。总之，受 DTβ4 启发的多孔 3DVGs 具有可调节的物理特性、优异的抗凝和再内皮化潜力，可促进小口径动脉的再生，因此为临床应用中的血管替代提供了一种有前途的工具。
