Peptides-tethered vascular grafts enable blood vessel regeneration via endogenous cell recruitment and neovascularization
Peptides-tethered vascular grafts enable blood vessel regeneration via endogenous cell recruitment and neovascularization
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DOI：
10.1016/j.compositesb.2023.110504
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
Yifan Wu;Lili Song;Muhammad Shafiq;H. Ijima;S. Kim;Ran Wei;Deling Kong;X. Mo;Kai Wang
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文献类型：
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作者：
Yifan Wu;Lili Song;Muhammad Shafiq;H. Ijima;S. Kim;Ran Wei;Deling Kong;X. Mo;Kai Wang
心血管损伤在世界范围内造成巨大的发病率和死亡率。动脉重建通常通过使用天然移植物或合成移植物来进行，这两种移植物都受到几种并发症的限制。合成的生物可降解聚合物提供了一个有前途的平台，也可以通过募集宿主细胞来修饰以促进原位组织再生。血管内皮生长因子（VEGF）促进血管移植物的内皮化和新生血管形成，然而，过量的VEGF可能诱导肿瘤样血管形成，这需要替代策略。本研究的目的是利用VEGF结合肽（BP）促进血管新生和内皮化，同时利用基质细胞衍生因子1 α（SDF-1α）肽促进内源性干/祖细胞动员和补充BP介导的血管重塑。将BP和SDF-1α肽分别与低分子量聚（ε-己内酯）（LPCL）共价偶联，得到LPCL-BP和LPCL-SDF-1α。化学分析表明，LPCL成功地被多肽修饰，并且在体外与高分子量PCL（HPCL）共混时也显示出良好的细胞相容性。通过将LPCL-BP、LPCL-SDF-1α或双肽聚合物缀合物与HPCL混合制成生物活性血管移植物。通过大鼠腹主动脉移植模型进行的血管移植物体内试验显示，与HPCL移植物相比，双肽修饰的移植物在植入后4周表现出更好的上级通畅性和组织再生，包括干细胞募集、快速内皮化和功能性SMC层形成。总而言之，这些结果可能对通过协调宿主反应和内源性细胞募集实现人工血管的原位再生产生影响。
Cardiovascular injuries cause huge morbidity and mortality worldwide. Arterial reconstructions are generally performed either by using native grafts or synthetic grafts, both of which are limited by several complications. Synthetic biodegradable polymers offer a promising platform, which may also be modified to fosterin situtissue regeneration through the recruitment of host cells. Vascular endothelial growth factor (VEGF) promotes endothelialization and neovascularization in vascular grafts, however, an overdose of VEGF may induce tumor-like vasculature, which requires alternative strategies. The objective of this study was to exploit prominin-1-derived VEGF-binding peptide (BP) to improve neovascularization and endothelialization, while stromal cell-derived factor 1-alpha (SDF-1α) peptide to encourage endogenous stem/progenitor cells mobilization and complement BP-mediated vascular remodeling. The BP and SDF-1α peptides were covalently conjugated with low molecular weight poly (ε-caprolactone) (LPCL) to afford LPCL-BP and LPCL-SDF-1α, respectively. Chemical analysis revealed successful modification of LPCL with peptides, which also displayed good cytocompatibilityin vitroonce blended along with high molecular weight PCL (HPCL). The bioactived vascular grafts were fabricated by blending LPCL-BP, LPCL-SDF-1α or dual peptide-polymer conjugates with HPCL. Thein vivotests of vascular grafts through rat abdominal aorta implantation model revealed that, compared with HPCL grafts, the dual peptides modified grafts exhibited superior patency and tissue regeneration at 4-week post-implantation, including stem cell recruitment, rapid endothelialization and functional SMC layer formation. Taken together, these results may have implications for thein situregeneration of artificial blood vessels through the orchestration of host's responses and endogenous cell recruitment.