Review

Bioengineered human blood vessels

See allHide authors and affiliations

Science  09 Oct 2020:
Vol. 370, Issue 6513, eaaw8682
DOI: 10.1126/science.aaw8682

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Evolution of bioengineered blood vessels

Biotechnology approaches to repair and replace arteries have been under development for more than a century. Early synthetic approaches used rubber-based replacements, which then evolved into the use of polymer fabrics and, more recently, into biological approaches that permit the growth of blood vessels in the laboratory. Niklason and Lawson review the scientific and technological advances that allow the regeneration of a patient's own blood vessels. The authors discuss how blood vessel cells, when combined with suitable substrates for tissue growth under conditions that mimic human physiology, can produce functional bioengineered arteries. These biological approaches pave the way to advancing how vascular disease is managed and treated in the future.

Science, this issue p. eaaw8682

Structured Abstract

BACKGROUND

Vascular replacement and repair for the treatment of atherosclerotic disease, infection, and traumatic injury are some of the most commonly performed surgical procedures in the Western world. In the United States alone, hundreds of thousands of coronary and peripheral arteries are repaired, replaced, or bypassed every year. But despite the enormity of the clinical need for engineered arterial replacements, the equally enormous simultaneous challenges of immune acceptance, requisite tissue mechanics, low thrombogenicity, and immediate availability have made the broad clinical application of engineered arteries quite difficult to achieve. In this regard, recent years have seen the fusion of cell biology, physiology, and engineering to now allow for the creation of human tissues that can truly function in the setting of vascular repair and replacement.

ADVANCES

For a biological engineered artery to function successfully without requiring immunosuppression, the following objectives should be met: (i) The engineered artery should have an extracellular matrix of sufficient quality to provide suitable tensile, suture retention, and rupture strength properties. A focus on production of suitable amounts of high-quality cross-linked vascular collagens type I and III is probably necessary for any biological engineered artery to be successful. (ii) To minimize risks of inflammation, foreign-body response, and immune recognition, the vascular tissue matrix should be of human origin and without substantial synthetic material additives or artificial covalent cross-linking. (iii) If the engineered artery is cellular, even if the cells are nonviable, those cells should be autologous to prevent immune recognition, degradation, and aneurysm formation in the implanted vessels. (iv) Once implanted, the engineered arteries should have the potential to be remodeled, repopulated, and rejuvenated by the host. (v) For small-caliber or low-flow arterial bypass applications, it is likely that a suitable nonthrombogenic luminal surface is required. This surface may be either cellular or biochemical, but it should prevent blood coagulation contact activation, platelet adhesion and activation, and thrombosis in the arterial system.

OUTLOOK

Guided by the design criteria above, engineered blood vessels have been developed by several groups that have progressed to clinical trials. Recent clinical studies have demonstrated the feasibility of using human tissue–engineered blood vessels in the settings of vascular trauma, peripheral arterial disease, and vascular access for hemodialysis. Engineered arteries reaching the clinical domain have been composed of autologous cells or allogeneic cells, or have been engineered from allogeneic cells or tissues and then decellularized. Vascular functionality in patients has been demonstrated in both low-pressure environments (pediatric cardiac surgery) and high-pressure environments (peripheral arterial surgery in adults).

Autologous cell approaches have shown some promise, particularly in clinical settings of venous reconstruction and low pressure and in pediatric populations. However, scaling production of engineered arteries to tens of thousands of vessels per year, as would be needed to treat arterial atherosclerosis at large scale, presents enormous logistical challenges if autologous cell sources are used. Hence, it is likely that future successes of engineered arteries will employ allogeneic human cells or cell banks to generate tissues at clinically relevant scales, and suitable strategies will be required to prevent adaptive immunity and rejection of these vessels. Furthermore, next-generation techniques such as three-dimensional bioprinting of both cells and matrix may one day allow vessel production at accelerated speeds, possibly producing usable tissues in hours or days, rather than weeks or months. Microvascular and cardiac tissue engineering are also making important strides, pointing toward a future that could enable revascularization of solid organs. The evolution of scientific thinking and approaches that have brought us to this point is summarized in this review.

An engineered human artery cultured from human vascular cells and implanted into a patient.

Immunostaining for smooth muscle (red), progenitor cells (green), and cell nuclei (blue) shows extensive cellular repopulation of the engineered vessel. Engineered cells were implanted into the patient for 4 years. The layer of red-staining cells at the bottom of the image shows the repopulated engineered vessel wall. Blue staining at the top shows the nuclei of skin cells.

Abstract

Since the advent of the vascular anastomosis by Alexis Carrel in the early 20th century, the repair and replacement of blood vessels have been key to treating acute injuries, as well as chronic atherosclerotic disease. Arteries serve diverse mechanical and biological functions, such as conducting blood to tissues, interacting with the coagulation system, and modulating resistance to blood flow. Early approaches for arterial replacement used artificial materials, which were supplanted by polymer fabrics in recent decades. With recent advances in the engineering of connective tissues, including arteries, we are on the cusp of seeing engineered human arteries become mainstays of surgical therapy for vascular disease. Progress in our understanding of physiology, cell biology, and biomanufacturing over the past several decades has made these advances possible.

View Full Text

Stay Connected to Science