Available online at www.sciencedirect.
com Current Opinion in
ScienceDirect
The future of biomedical engineering – Vascular
bioengineering
Alison L. Marsden and George A. Truskey
Current Opinion in Biomedical
Engineering 2018, 5:iii–v
This review comes from a themed issue on
Futures of Biomedical Engineering: Cardio-
vascular Bioengineering
Edited by George A. Truskey
https://doi.org/10.1016/j.cobme.2018.04.002
2468-4511/© 2018 Published by Elsevier Inc.
Alison L. Marsden
Department of Pediatrics and Bioengi-
neering, Stanford University, Palo Alto, CA,
USA
George A. Truskey
Department of Biomedical Engineering,
Duke University, Durham, NC, USA
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Biomedical Engineering
Despite several decades of advances in the detection, treatment, and
management of cardiovascular disease, complications from cardiovascular
disease remain the leading cause of death throughout the world (http://
www.who.int/mediacentre/factsheets/fs310/en/). Proper management of
cholesterol levels, declines in percentage of the population who smoke in
Europe and the United States, and improved methods to treat symptoms
of angina and fibrillation have led to a reduction in sudden cardiac death.
As a result, cardiovascular disease can be treated as a chronic problem to be
managed. Nonetheless, smoking rates are increasing in many other parts of
the world, including China [1], and levels of other risk factors such as type
2 diabetes and obesity, are increasing worldwide (http://www.who.int/
mediacentre/factsheets/fs312/en/). Levels of hypertension still remain
high and the disease pathogenesis is poorly understood so that treatment
address the symptoms without resolving the underlying disease mecha-
nism. Further, rates of heart failure are rising, as survivors of heart attacks
still have significant damage to their hearts. While public health efforts are
needed to improve diet and lifestyle to reduce the role of the key risk
factors, research needs to be directed at understanding the complex
events following cardiovascular events that cause tissue damage and long-
term health problems.
Bioengineering has much to offer in identifying cardiovascular disease
pathology, as well as the detection and treatment of disease. We now have
a general understanding that the forces acting on arteries and the me-
chanical behavior of arteries influences disease onset and development.
Temporal patterns of fluid shear stresses around vessel branches and in
curved vessels are closely associated with the initiation of atherosclerosis,
and mechanicals tresses on arteries affects the shear stress distribution
and the behavior of smooth muscle cells [2]. This results in changes in the
function of vascular endothelium and the local mechanical properties
where lesions develop [3]. Companion articles in the issue on Vascular
Biomechanics review recent advances in methods to characterize forces at
the cellular and tissue level.
While many of the cellular pathways in vascular endothelium are influ-
enced by changes in shear stress have been identified, how these pathways
interact in normal development and under disease conditions is poorly
understood. Abuammah et al. [4] discuss how three critical signaling
pathways are activated by fluid shear stress (Wnt, Notch, and TGF-b).
They highlight the need for continued study of the ways in which in-
teractions among these pathways may influence the response of vascular
endothelium in various flow regimes.
Current Opinion in Biomedical Engineering 2018, 5:iii–v
iv Futures of Biomedical Engineering: Cardiovascular Bioengineering
Another fundamental role of the vascular system is to
integrate the immune response by transporting white
blood cells, cytokines, chemokines in different tissues.
In particular, gradients in cytokines and chemokines
between the blood and the lymphatic system can affect
the inflammatory response. The role of concentration
gradients of these molecules has often been overlooked
by immunologists. Moore et al. [5] describe how
mathematical models of the transport processes and
binding reactions in tissues and lymphatics can be used
to explain experimental results involving chemokines.
Such efforts could affect the development and applica-
tion of therapies.
Bioengineers are playing a critical role in the devel-
opment of new approaches for the identification and
treatment of cardiovascular diseases. Trayanova and
colleagues discuss recent effort to integrate computa-
tional models of cardiac activity with imaging to
improve the diagnosis and treatment of cardiovascular
disease [6]. Computational models can be developed
using patient-specific information and visualization of
simulation results can be used to make decisions about
different clinical procedures or stratify the patient’s
risk.
Tissue engineering strategies to replace damaged or
diseased valves and blood vessels are moving closer to
clinical application. While heart valve replacement with
synthetic valves work well in general, children with
congenital defects need a natural valve that can grow
and adapt as they age, while the elderly need procedures
that require minimal surgical intervention. The current
status of various strategies to engineer a natural valve
replacement is reviewed by Zhu and Grande-Allen [7].
Different strategies may be needed depending on the
location of the valves to be replaced. The authors
identify several challenges to be addressed in devel-
oping an ideal valve replacement. Engineered vascular
grafts can now be fabricated with the requisite me-
chanical strength to enable replacement [8]. Acellular
grafts can be used in vessels with high flow rates, but for
smaller vessels, an endothelial layer is necessary to
prevent thrombosis. Mesenchymal stem cells represent
a potential cell type that could serve as a replacement of
vascular endothelium and the medial cells. These cells
exhibit low immunogenicity ad can be made to express
many of the anti-inflammatory and anti-thrombotic
molecules expressed by endothelial cells [8].
Biomechanics also plays a key role in tissue engineering
and regeneration, particularly in controlling the differ-
entiation of human pluripotent stem cells. Biomechan-
ical cues that determine differentiation into smooth
muscle and endothelial cells are discussed and reviewed
by Chan, Eoh, and Gerecht [9]. Not only are mechanical
factors important in directing cell fate, but they can also
enhance functionality of differentiated cells. These
Current Opinion in Biomedical Engineering 2018, 5:iii–v
processes play a key role in the field of cell therapy and
tissue engineering constructs.
Recently, a number of in vitro model systems have been
developed that replicate various features of cardiovas-
cular system including microvasculature [10,11], the
blood brain-barrier [12], and thrombosis [13]. The cul-
ture system and the presence of other cell types can
affect the properties of the endothelium and can be
used to differentiate the endothelium to different
tissue-specific forms. Fabrication methods enable a wide
variety of possible applications for vascularized endo-
thelialized channels. Alternatively, self-assembly of
capillary network in a model tissue consisting of stromal
cells and extracellular matrix more closely resembles the
in vivo environment and model cancer metastasis [10].
Although the overall flow across these capillary networks
can be controlled, the flow in individual capillaries
cannot. By controlling the cellular composition of the
media and the presence of prothrombotic and procoa-
gulant molecules, various aspects of thrombosis and
inflammation can be studied.
While the importance of monocytes and macrophages in
the innate immune system are well appreciated, recent
work has uncovered previously lesser-known roles of
these key cells in valvular development and disease
[14]. The review of Sridhar et al. highlights the contri-
butions of monocytes and macrophages throughout the
valvulogenic process and use in tissue engineering.
Disease applications and treatments are also a key focus
of bioengineering studies. Thoracic aortic aneurysms,
characterized by a dilated aorta, lead to high risks of
rupture and aortic dissection. The progression and
treatment of these aneurysms are influenced by the bio-
chemo-mechanical environment of the abdominal aorta.
The review of Wagenseil outlines and links the roles of
fluid and solid mechanics, as well as cell phenotype,
chemical signaling, and matrix composition in this
complex disease process. Recently studies using biaxial
deformation, computational fluid dynamics, and me-
chanical transduction are summarized [15].
Finally, mechanical stimuli have important effects on
vascular mechanobiology, both at the tissue and cellular
level. Individual cells are exposed to a variety of stimuli
from pressure, muscle contraction, and fluid shear
forces. Fleissner and Parekh review molecular to cellular
level imaging methods for quantification of local de-
formations and forces leading to changes in cellular
physiology [16]. Traction force microscopy is one of the
most important techniques to characterize forces exer-
ted by cells on their substrates. By taking advantage of
major advances in light microscopy and image analysis,
this technique continues to provide important infor-
mation about the forces cells exert and ways in which
mechanotransduction occurs [17].
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Editorial Overview Marsden and Truskey v
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Current Opinion in Biomedical Engineering 2018, 5:iii–v