Fabricating Blood Vessels with Ultrasound

Diane Dalecki, Ph.D.
Eric S. Comeau, M.S.
Denise C. Hocking, Ph.D.
Rochester Center for Biomedical Ultrasound
University of Rochester
Rochester, NY 14627

Popular version of paper 3aBA5, “Applications of acoustic radiation force for microvascular tissue engineering”
Presented Wednesday morning May 20, 9:25 AM, in room Kings 2
169th ASA Meeting, Pittsburgh

Tissue engineering is the field of science dedicated to fabricating artificial tissues and organs that can be made available for patients in need of organ transplantation or tissue reconstructive surgery. Tissue engineers have successfully fabricated relatively thin tissues, such as skin substitutes, that can receive nutrients and oxygen by simple diffusion. However, recreating larger and/or more complex tissues and organs will require developing methods to fabricate functional microvascular networks to bring nutrients to all areas of the tissue for survival.

In the laboratories of Diane Dalecki, Ph.D. and Denise C. Hocking, Ph.D., research is underway to develop new ultrasound technologies to control and enhance the fabrication of artificial tissues1. Ultrasound fields are sound fields at frequencies higher than humans can hear (i.e., > 20 kHz). Dalecki and Hocking have developed a technology that uses a particular type of ultrasound field, called an ultrasound standing wave field, as a tool to non-invasively engineer complex spatial patterns of cells2 and fabricate microvessel networks3,4 within artificial tissue constructs.

When a solution of collagen and cells is exposed to an ultrasound standing wave field, the forces associated with the field lead to the alignment of the cells into planar bands (Figure 1). The distance between the bands of cells is controlled by the ultrasound frequency, and the density of cells within each band is controlled by the intensity of the sound field. The collagen polymerizes into a solid gel during the ultrasound exposure, thereby maintaining the spatial organization of the cells after the ultrasound is turned off. More complex patterning can be achieved by use of more than one ultrasound transducer.

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Figure 1. Acoustic-patterning of microparticles (dark bands) using an ultrasound standing wave field. Distance between planar bands is 750 µm. Scale bar = 100 μm

An exciting application of this technology involves the fabrication of microvascular networks within artificial tissue constructs. Specifically, acoustic-patterning of endothelial cells into planar bands within collagen hydrogels leads to the rapid development of microvessel networks throughout the entire volume of the hydrogel. Interestingly, the structure of the resultant microvessel network can be controlled by choice of the ultrasound exposure parameters. As shown in Figure 2, ultrasound standing wave fields can be employed to fabricate microvessel networks with different physiologically relevant morphologies, including capillary-like networks (left panel), aligned non-branching vessels (center panel) or aligned vessels with hierarchically branching microvessels. Ultrasound fields provide an ideal technology for microvascular engineering; the technology is rapid, noninvasive, can be broadly applied to many types of cells and hydrogels, and can be adapted to commercial fabrication processes.

To learn more about this research, please view this informative video (https://www.youtube.com/watch?v=ZL-cx21SGn4).

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Figure 2. Ultrasound-fabricated microvessel networks within collagen hydrogels. The ultrasound pressure amplitude used for initial patterning determines the final microvessel morphology, which can resemble torturous capillary-like networks (left panel), aligned non-branching vessels (center panel) or aligned vessels with hierarchically branching microvessels. Scale bars = 100 μm.

References:

[1] Dalecki D, Hocking DC. Ultrasound technologies for biomaterials fabrication and imaging. Annals of Biomedical Engineering 43:747-761; 2015.

[2] Garvin KA, Hocking DC, Dalecki D. Controlling the spatial organization of cells and extracellular matrix proteins in engineered tissues using ultrasound standing wave fields. Ultrasound Med. Biol. 36:1919-1932; 2010.

[3] Garvin KA, Dalecki D, Hocking DC. Vascularization of three-dimensional collagen hydrogels using ultrasound standing wave fields. Ultrasound Med. Biol. 37:1853-1864; 2011.

[4] Garvin KA, Dalecki D, Youssefhussien M, Helguera M, Hocking DC. Spatial patterning of endothelial cells and vascular network formation using ultrasound standing wave fields. J. Acoust. Soc. Am. 134:1483-1490; 2013.

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