The invention use ultrasound to non-invasively and site-specifically control collagen fiber microstructure within three-dimensional (3D) engineered tissues.

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 Brief Description: The invention use ultrasound to non-invasively and site-specifically control collagen fiber microstructure within three-dimensional (3D) engineered tissues.   Applications: The invention can be developed for generating engineered tissues with spatial variations in mechanical strength, which could be useful for fabricating striated tissues, such as tendon and ligament; producing an artificial skin product with enhanced mechanical strength; and producing layered tissues, such as articular cartilage. Also, this technology can be applied for developing engineered tissues with spatial differences in cell functions, such as cell migration, adhesion, and/or proliferation, which could be useful for fabricating an implant for directed nerve regeneration; producing directed cell migration into central cores of engineered tissues; controlling cell adhesion in a site-specific manner within engineered tissues; controlling stem cell differentiation within engineered tissues; as well as engineering tissues with complex cell spatial organization, such as liver and pancreas This invention has the potential to recreate inhomogeneities naturally present with ECM of native tissues and thus, could advance the fabrication of functional artificial tissues and organs in vitro.     Advantages: The ability to non-invasively control collagen microstructure within 3-D engineered tissue provides the opportunity to produce artificial tissues for numerous novel applications. The technology can be used with standard cell culture supplies and incorporated into bioreactor designs. Implementation of the invention in a commercial setting will not require drastic changes to common operating practices with cell and tissue engineering laboratories.  

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