Prototype Graft Designed To Replace Damaged Heart Vessels Shows Promise In Cell Study

Researchers used a circular knitting machine to make a prototype of a replacement for a coronary artery. Image courtesy of Fan Zhang.

Knitted vascular graft prototype shows promise in preclinical findings.

劳拉·奥利亚茨(Laura Oleniacz)

n概念验证研究,总部位于北卡罗来纳州北卡罗来纳州立大学(NC州立大学)研究人员报告了有希望的临床前发现,用于替代受损或阻塞的冠状动脉的血管移植物的原型心。

The findings, which were made in partnership with researchers from Case Western Reserve University, are part of an effort to develop a man-made graft that could replace a damaged or blocked coronary artery when a patient’s own vessels are not available as viable replacements after a heart attack. Ultimately, the graft is designed as a scaffold to aid in regeneration of the patient’s own blood vessels. And while their work is still in early stages, the researchers said their design will help to move the field forward.

我n the journal材料科学与工程:C研究人员报告说,他们通过用人造纱线编织胶原蛋白材料制作了原型的血管移植物。他们发现,与单独使用胶原蛋白材料的模型相比,他们的设计表现出了提高的强度,并且与人类冠状动脉相比的柔韧性。同样,在对人内皮细胞的研究中,他们看到了细胞在移植物上的生长和粘附增加,这表明它可以有助于冠状动脉衬里的再生。

该研究的高级作者马丁·金(Martin King)说:“我们认为这是研究冠状动脉替代移植物的新方向。”“使用胶原蛋白非常新。我们不仅依赖一种材料,而且还将材料混合在一起,并表明这两条纱线可以提供机械强度和我们正在寻找的生物学反应。”

Currently, researchers said the “gold standard” is to use a patient’s own blood vessel, such as a vein from the leg or the mammary artery, to replace the coronary artery, but some patients do not have viable blood vessels that can be harvested and used.

这项研究的第一作者兼研究生张张说:“有必要为这种患者找到另一种解决方案。”“这就是为什么我们寻求使用组织工程的血管移植物的原因。”

研究人员说,设计可以替代冠状动脉的合成血管移植物存在许多挑战。由于动脉凝结和狭窄的问题,一些模型失败了。同时,其他模型无法用跳动的心伸展和放松。

“The coronary artery is only about three to four millimeters in diameter so it’s a very fine artery, and it’s very easy for it to get blocked,” King said. “The question is: Do we have materials that will serve as a conduit without provoking this clotting on the arterial wall? That is one of the challenges. The other is that the heart is continually expanding and contracting, so we need a structure that can stretch and relax with every heartbeat.”

混合纱是使用胶原蛋白和由聚乳酸组成的人造纤维制成的。图片由北卡罗来纳州立大学研究生Jiyang Chen提供。

To develop their design, the NC State investigators collaborated with researchers at Case Western Reserve who have designed a biological yarn made of collagen. They combined that collagen yarn with a man-made fiber made of polylactic acid (PLA), which is biocompatible. When the fiber degrades, it forms lactic acid, researchers said, which is easily tolerated because the muscles in our bodies continuously generate lactic acid.

研究人员说,他们的模型旨在形成一个临时脚手架,可以再生与患者自己的血管相似的细胞衬里。

金说:“我们没有设计一种原型,它是'最终产品',我们正在放入将患者治愈并使用这种结构来治愈和发挥冠状动脉的成分。”“纤维最终会降解并吸收到体内。”

研究人员发现,通过针织胶原fibers together with the man-made PLA yarn, human endothelial cells stuck to the scaffold 10 times as much as to the man-made yarn alone. The experiment also showed three times greater cell growth after adhesion.

此外,他们发现它具有出色的爆发强度和合规性,这些特性将使移植物与每个心跳扩张并收缩 - 类似于健康的冠状动脉。

“We were able to mimic the compliance of the coronary artery,” Zhang said. “This is the most important finding. In addition, with the addition of the collagen yarn component, we were able to promote endothelial cells to grow faster within this structure. That is very important for recovery of the endothelium.”

Their work is still at a preclinical stage and has yet to be tested in a living animal. They still have work to improve their prototype to overcome additional design challenges, including how to reduce the porous nature of the hybrid graft.

但是,该小组认为他们的发现表明,可以将生物和人造材料结合在人造冠状动脉移植物的设计中。他们正在采用解决方案以防止血液泄漏。

“With this combination of materials, we have been able to balance the mechanical performance with the biological response,” King said. “We were also able to manufacture the prototype graft using high speed textile production machinery, which will facilitate future manufacturing scale-up and translation to a commercial graft and the clinic.”

The paper, “A hybrid vascular graft harnessing the superior mechanical properties of synthetic fibers and the biological performance of collagen filaments,” was published online in材料科学与工程,C部分。该论文由Tushar Bambharoliya,Yu Xie,Laijun Liu,Hakan Celik,Lu Wang和Ozan Akkus共同撰写。东华大学(Donghua University)由中国教育部和AATCC基金会学生研究支持拨款提供的1,1,1项目B07024赠款提供了支持。


编者注:Laura Oleniacz是NC State News Services的公共传播专家。


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