scholarly journals Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide

Author(s):  
Sen Yang ◽  
Xueni Zheng ◽  
Meng Qian ◽  
He Wang ◽  
Fei Wang ◽  
...  

Artificial small-diameter vascular grafts (SDVG) fabricated from synthetic biodegradable polymers, such as poly(ε-caprolactone) (PCL), exhibit beneficial mechanical properties but are often faced with issues impacting their long-term graft success. Nitric oxide (NO) is an important physiological gasotransmitter with multiple roles in orchestrating vascular tissue function and regeneration. We fabricated a functional vascular graft by electrospinning of nitrate-functionalized poly(ε-caprolactone) that could release NO in a sustained manner via stepwise biotransformation in vivo. Nitrate-functionalized SDVG (PCL/NO) maintained patency following abdominal arterial replacement in rats. PCL/NO promoted cell infiltration at 3-months post-transplantation. In contrast, unmodified PCL SDVG showed slow cell in-growth and increased incidence of neointima formation. PCL/NO demonstrated improved endothelial cell (EC) alignment and luminal coverage, and more defined vascular smooth muscle cell (VSMC) layer, compared to unmodified PCL SDVG. In addition, release of NO stimulated Sca-1+ vascular progenitor cells (VPCs) to differentiate and contribute to rapid luminal endothelialization. Furthermore, PCL/NO inhibited the differentiation of VPCs into osteopontin-positive cells, thereby preventing vascular calcification. Overall, PCL/NO demonstrated enhanced cell ingrowth, EC monolayer formation and VSMC layer regeneration; whilst inhibiting calcified plaque formation. Our results suggested that PCL/NO could serve as promising candidates for improved and long-term success of SDVG implants.


Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3678
Author(s):  
Vera Chernonosova ◽  
Alexandr Gostev ◽  
Ivan Murashov ◽  
Boris Chelobanov ◽  
Andrey Karpenko ◽  
...  

We examined the physicochemical properties and the biocompatibility and hemocompatibility of electrospun 3D matrices produced using polyurethane Pellethane 2363-80A (Pel-80A) blends Pel-80A with gelatin or/and bivalirudin. Two layers of vascular grafts of 1.8 mm in diameter were manufactured and studied for hemocompatibility ex vivo and functioning in the infrarenal position of Wistar rat abdominal aorta in vivo (n = 18). Expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar diameter were implanted as a control (n = 18). Scaffolds produced from Pel-80A with Gel showed high stiffness with a long proportional limit and limited influence of wetting on mechanical characteristics. The electrospun matrices with gelatin have moderate capacity to support cell adhesion and proliferation (~30–47%), whereas vascular grafts with bivalirudin in the inner layer have good hemocompatibility ex vivo. The introduction of bivalirudin into grafts inhibited platelet adhesion and does not lead to a change hemolysis and D-dimers concentration. Study in vivo indicates the advantages of Pel-80A grafts over ePTFE in terms of graft occlusion, calcification level, and blood velocity after 6 months of implantation. The thickness of neointima in Pel-80A–based grafts stabilizes after three months (41.84 ± 20.21 µm) and does not increase until six months, demonstrating potential for long-term functioning without stenosis and as a suitable candidate for subsequent preclinical studies in large animals.



2020 ◽  
Vol 85 ◽  
pp. 1-6
Author(s):  
Chengjin Wang ◽  
Zhen Li ◽  
Lei Zhang ◽  
Wei Sun ◽  
Jianye Zhou


2011 ◽  
Vol 22 (1-3) ◽  
pp. 195-206 ◽  
Author(s):  
Yasumoto Nakazawa ◽  
Michiko Sato ◽  
Rui Takahashi ◽  
Derya Aytemiz ◽  
Chiyuki Takabayashi ◽  
...  


Biomaterials ◽  
2010 ◽  
Vol 31 (9) ◽  
pp. 2592-2605 ◽  
Author(s):  
Giorgio Soldani ◽  
Paola Losi ◽  
Massimo Bernabei ◽  
Silvia Burchielli ◽  
Dante Chiappino ◽  
...  


2020 ◽  
Vol 43 (10) ◽  
pp. 631-644 ◽  
Author(s):  
Justine Cordelle ◽  
Sara Mantero

Along with an increased incidence of cardiovascular diseases, there is a strong need for small-diameter vascular grafts. Silk has been investigated as a biomaterial to develop such grafts thanks to different processing options. Endothelialization was shown to be extremely important to ensure graft patency and there is ongoing research on the development and behavior of endothelial cells on vascular tissue-engineered scaffolds. This article reviews the endothelialization of silk-based scaffolds processed throughout the years as silk non-woven nets, films, gel spun, electrospun, or woven scaffolds. Encouraging results were reported with these scaffolds both in vitro and in vivo when implanted in small- to middle-sized animals. The use of coatings and heparin or sulfur to enhance, respectively, cell adhesion and scaffold hemocompatibility is further presented. Bioreactors also showed their interest to improve cell adhesion and thus promoting in vitro pre-endothelialization of grafts even though they are still not systematically used. Finally, the importance of the animal models used to study the right mechanism of endothelialization is discussed.



2020 ◽  
Vol 8 (26) ◽  
pp. 5694-5706
Author(s):  
Yizao Wan ◽  
Shanshan Yang ◽  
Mengxia Peng ◽  
Miguel Gama ◽  
Zhiwei Yang ◽  
...  

A novel small-diameter graft consisting of nanofibrous bacterial cellulose and submicrofibrous cellulose acetate was prepared and evaluated in vitro and in vivo.



2019 ◽  
Vol 14 (12) ◽  
pp. 1089-1105 ◽  
Author(s):  
XiangYun Zhang ◽  
Jie Shi ◽  
SiYuan Chen ◽  
YunSheng Dong ◽  
Lin Zhang ◽  
...  

Aim: Host remolding with scaffolds degradation and rapid formation of a complete endothelium, are prospective solutions for improving performance of small diameter vascular grafts. Materials & methods: For this purpose, microfibrous polycaprolactone (PCL)/gelatin scaffolds were prepared by electrospinning and subsequently functionalized with heparin and organoselenium-immobilized polyethyleneimine for nitric oxide generation through layer-by-layer self-assembly. Results: Our results showed that modified PCL/gelatin grafts had strong catalytic nitric oxide generation capacity and facilitated the enhanced attachment of endothelial cells, compared with control scaffold groups. Meanwhile, the modified grafts exhibited good hemocombatility, rapid endothelialization and smooth muscle cell regeneration. Conclusion: Modification of biodegradable scaffolds, proposed in this work, could enhance biological functions of vascular grafts and provides new strategies for the construction of small diameter vascular grafts.



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