Biomedical Engineering Reference
In-Depth Information
sized fibers.
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ECs attached to the inner nanoscale fibers in a confluent monolayer,
which was confirmed by CD31 staining. SMCs were shown to infiltrate the more
porous outer layer, with
-smooth muscle actin (SMA) present throughout.
Electrospinning nanofibers is a simple and controllable method to produce ECM-
mimicking fibers to fabricate tissue-engineered vascular grafts. Engineers must
continue to adapt electrospinning techniques to overcome the current limitations.
Additionally, progress had been made by combining electrospun fibers with other
micro- and nanofabrication techniques. Researchers should continue to look for
synergistic combinations to produce clinically successful tissue-engineered vascular
grafts.
a
11.6 MICROVASCULAR TISSUE ENGINEERING
11.6.1 Need for Microvascular Networks in Tissue Engineering
Apart from designing macroscale vascular constructs, vascular tissue engineering is
focused on de novo development of microvascular networks. Thin or avascular tissue
engineering products have been successful in the clinic,
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but bulk constructs have
proven challenging because cells seeded within the scaffolds must rely on diffusion
to provide oxygen and nutrients necessary for viability, proliferation, and remodel-
ing. Thus, the thickness of the construct becomes the limiting factor. Studies have
shown that cells cannot survive more than a few hundred micrometers from a
capillary source.
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Creating or developing robust vascular networks within tissue
engineering scaffolds is critical to the continued success of the field. Toward this
goal, microfluidics and microfabrication techniques have been used to gain precise
control of geometry, architecture, and flow within a construct.
11.6.2 Microfluidics
As awareness of the need to vascularize tissue-engineered constructs became
apparent, researchers looked to the field of microfluidics as an attractive system
for controlling size, branching, and flow in a precise manner. The initial contributions
in this field were made by Bornstein and Vacanti. Bifurcated patterns were fabricated
using photolithography in silicon and Pyrex, and ECs and hepatocytes were cultured
in the device (Fig. 11.2a and b).
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The cells were lifted from the surface as a
monolayer and maintained their proliferative capacity and functionality. The lifted
ECs also aligned to form branched networks, reminiscent of native capillary
structures. Further studies were performed using soft lithography to mold poly-
dimethylsiloxane (PDMS) on silicon wafers.
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Although this pioneering work demonstrated the ability to engineer microfluidic
systems and successfully culture cells within them, the materials used did not lend
themselves to tissue engineering applications because of their limited bio-
compatibility and nonbiodegradable nature.
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King et al. used the biodegradable
polymer PLGA to form microfluidic systems.
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However, PLGA is a brittle material
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