Creating artificial microvessel networks that structurally and functionally mimic the native microvasculature is critical for the fabrication and survival of a wide range of bioengineered tissues, and will also provide realistic cost-effective i vitro models for drug discovery, product testing and toxicology screening. We have recently developed an innovative, non-invasive ultrasound-based method to spatially pattern cells within 3D hydrogels, and have demonstrated the feasibility of translating ultrasound technologies to microvascular tissue engineering. We have shown that acoustic radiation forces associated with ultrasound standing wave fields (USWF) can rapidly organize cells into distinct multicellular planar bands within 3D collagen gels. USWF-induced patterning of endothelial cells rapidly initiates the assembly of complex, branching vessel networks throughout the volume of the hydrogel. Importantly, the rate of formation as well as the morphology of resultant microvascular networks can be controlled by design of the acoustic field. The goal of this project is to advance the use of USWF technologies as a versatile, non-invasive method to vascularize hydrogels in vitro, with the ultimate goal of translating this technique to in situ vascularization. To do so, w will (1) identify USWF exposure parameters that stimulate microvessel assembly and control microvessel structure, (2) identify critical biological parameters that influence the structure and function of USWF-fabricated microvascular networks, and optimize their usage for in vitro and in situ fabrication, and (3) assess the in vivo performance of USWF hydrogel constructs fabricated in vitro and in situ. Non-invasive ultrasound-based technologies that can rapidly organize cells into distinct geometric patterns, either in vitro or in situ, will be broadly applicable across cel and tissue types, and thus, are expected to have a wide impact on advancing tissue engineering and regenerative medicine.

Public Health Relevance

Tissue engineering is a potentially revolutionary approach for replacing or regenerating damaged organs and tissues. Creating large, complex tissues is currently limited by an inability to adequately vascularize engineered tissues to maintain cell viability. Here, we develop a non-invasive, ultrasound-based technology to spatially organize cells within three-dimensional hydrogels to produce functional microvascular networks, in vitro and in situ.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
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Hunziker, Rosemarie
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University of Rochester
Schools of Dentistry
United States
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Farrar, Christopher S; Hocking, Denise C (2018) Assembly of fibronectin fibrils selectively attenuates platelet-derived growth factor-induced intracellular calcium release in fibroblasts. J Biol Chem 293:18655-18666
Comeau, Eric S; Hocking, Denise C; Dalecki, Diane (2017) Ultrasound patterning technologies for studying vascular morphogenesis in 3D. J Cell Sci 130:232-242
Dalecki, Diane; Mercado, Karla P; Hocking, Denise C (2016) Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials. Ann Biomed Eng 44:636-48
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Mercado, Karla P; Helguera, María; Hocking, Denise C et al. (2015) Noninvasive Quantitative Imaging of Collagen Microstructure in Three-Dimensional Hydrogels Using High-Frequency Ultrasound. Tissue Eng Part C Methods 21:671-82