Vascular Grafts with Tailored Stiffness and a Ligand Environment via Multiarmed Polymer Sheath for Expeditious Regeneration.

Vascular Grafts with Tailored Stiffness and a Ligand Environment via Multiarmed Polymer Sheath for Expeditious Regeneration.
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DOI:
10.1021/acsabm.0c01114
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发表时间:
2021-01-18
影响因子:
4.7
通讯作者:
Tan W
Tan W
中科院分区:
其他
文献类型:
--
作者:
Iglesias-Echevarria M;Johnson R;Rafuse M;Ding Y;Tan W

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旁路移植术是治疗血管疾病的主流外科手术。理想的旁路材料,尚未开发,需要机械性能,可用性,临床可行的制造物流,和生物活性与精确的物理化学线索定义,以指导动脉再生的细胞活动。这种需求促使我们制造血管移植物,其由同轴的纳米结构纤维组成,所述纤维表现出聚己内酯(PCL)芯和可光点击的4臂硫醇化聚乙二醇-己二烯(PEG-NB)鞘。接枝物的强度和生物活性分别受PCL浓度和PEG-NB的硫醇-烯结合肽(RGD、转化生长因子β-1或TGF-β1)的调节。结构、物理和机械表征表明,纤维移植物模仿天然细胞外基质的关键特征,包括用于结构稳定性的交联纤维网络、模拟动脉的粘弹性、水合性质和用于细胞浸润的高孔隙率。同时,这些移植物显示出超过或达到手术标准的强度和韧性。此外,具有较高PCL浓度(3%对1.8%)的移植物显示较厚的纤维、较低的孔隙率和孔径,以及增加的弹性模量和储能模量。通过间充质干细胞(MSC)在移植物上的行为和体内动脉再生来确定移植物的生物活性。结果表明,细胞的粘附和增殖能力随着RGD浓度的增加而增加(25 vs 5 mM)。在植入1周后,与PCL移植物相反,所有具有或不具有MSC预接种的肽功能化PCL/PEG-NB移植物显示出迅速的内皮衬里、丰富的血管细胞浸润和基质产生。与RGD移植物相比,RGD/TGF-β1移植物在体外促进MSC分化为平滑肌细胞,在体内形成更厚的平滑肌细胞层。总的来说,多功能多孔血管移植物具有优异的上级性能和可调性,可用于未来的平移。
The bypass graft is the mainstream of surgical intervention to treat vascular diseases. Ideal bypass materials, yet to be developed, require mechanical properties, availability, clinically feasible manufacturing logistics, and bioactivities with precise physicochemical cues defined to guide cell activities for arterial regeneration. Such needs instigated our fabrication of vascular grafts, which consist of coaxial, nanostructured fibers exhibiting a polycaprolactone (PCL) core and a photoclickable, 4-arm thiolated polyethylene glycol-norbornene (PEG-NB) sheath. The graft strength and bioactivity were modulated by the PCL concentration and the peptides (RGD, transforming growth factor β-1 or TGF-β1) conjugated to thiol–ene of PEG-NB, respectively. Structural, physical, and mechanical characterizations demonstrated that the fibrous grafts mimicked the key features of the native extracellular matrix, including a crosslinked fiber network for structural stability, viscoelasticity emulating arteries, hydration property, and high porosity for cell infiltration. Meanwhile, these grafts displayed strength and toughness exceeding or meeting surgical criteria. Furthermore, the grafts with higher PCL concentration (3 vs 1.8%) showed thicker fibers, lower porosity and pore size, and increased elastic and storage moduli. Graft bioactivity was determined by the mesenchymal stem cell (MSC) behaviors on the grafts and arterial regeneration in vivo using interposition grafting. Results showed that the cell adhesion and proliferation increased with the RGD density (25 vs 5 mM). After 1 week implantation, all peptide-functionalized PCL/PEG-NB grafts with or without MSC preseeding, as opposed to PCL grafts, showed expeditious endothelial lining, abundant vascular cell infiltration, and matrix production. Compared to RGD grafts, RGD/TGF-β1 grafts enhanced MSC differentiation into smooth muscle cells in vitro and developed thicker smooth muscle cell layers in vivo. Overall, the versatile porous vascular grafts offer superior properties and tunability for future translation.
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