SBIR-STTR Award

This Small Business Innovation Research Phase II project will develop a commercially-viable device that uses micro-scale acoustic streaming (low frequency sound energy) to deliver mixing to the interior of three-dimensional (3D) scaffolds used for stem cell cultivation applications. The enabling advantage of low frequency sound energy is the ability to generate micro-scale mixing in and around scaffolds that can enhance the movement of liquid, molecules, and oxygen within scaffolds without the need for pumps or a costly and inconvenient perfusion apparatus for each scaffold. Preliminary data shows that cells can successfully grow in the presence of the acoustic energy field. Nutrient supply issues and difficulties in homogenously seeding dense scaffolds are issues that need to be overcome in order to successfully produce high quality, repeatable cell cultures in the complex 3D environments that are the mainstay of modern stem cell and tissue engineering. Many possible solutions to these problems have been examined, including the use of spinner flask, centrifugal, vacuum fixtures, or perfusion for cell seeding. The vision for the approach proposed here is to develop a single bioreactor platform on which multiple scaffolds can be mounted in simple fixtures to deliver similar benefits as those derived from complex perfusion bioreactors but without the significant time and capital investment inherent in such an approach. When used at low intensities, the proposed device should be able to deliver benefits similar to a perfusion bioreactor, but in a much simpler package. When used at higher intensities in the absence of cells, additional applications and benefits of the proposed product will be delivered in the form of much more rapid methods for the hydration, functionalization, and enzymatic degradation of scaffolds. The goal of this research proposal is to build a commercial prototype Acoustic Scaffold Bioreactor device and to extensively characterize and optimize its use for scaffold-based hematopoietic and mesenchymal stem cell culture systems. The commercial applications of the device will be broad within the field of stem cell and tissue engineering, extending to the full range of cells and tissues that have shown to be enhanced by more cumbersome perfusion flow-based systems, as well as to basic operations such as hydrating, functionalizing, and digesting scaffolds.

Public Health Relevance Statement:
This Small Business Innovation Research Phase II project will develop and demonstrate an Acoustic Scaffold Bioreactor (ASB) that employs a novel agitation method in the form of low-frequency sound energy. By greatly enhancing the penetration of liquids, molecules, and cells into the very small pores of natural and artificial scaffolds used for stem cell cultivation applications, the ASB will provide a low-cost, easy-to-use method of enhancing cellular growth and seeding within scaffolds. Better culture performance and cost-savings without the use of complex pumps and tubing will translate to more affordable stem cell-derived therapeutic products and better patient outcomes.

Project Terms:
Acoustics; Adherent Culture; Agitation; base; Biocompatible Materials; Bioreactors; Biotechnology; Capital; Carbon Dioxide; Cell Culture System; Cell Culture Techniques; cell growth; cell injury; Cell Line; cell type; Cells; cellular engineering; commercial application; Complex; cost; Cost Savings; Cultured Cells; Data; design; design and construction; Development; Devices; Dimensions; Environment; Evaluation; exhaustion; flasks; Frequencies; Future; Goals; Growth; Guidelines; Hematopoietic; Hematopoietic stem cells; High temperature of physical object; Humidity; Hydration status; improved; Industrialization; Infusion Pumps; Investments; Laboratories; Liquid substance; Mesenchymal Stem Cells; Methods; Modeling; Modernization; Movement; new technology; novel; novel strategies; Nutrient; operation; Oxygen; Patient-Focused Outcomes; Penetration; Performance; Perfusion; Phase; Process; Productivity; Protocols documentation; prototype; Pump; rapid technique; Regenerative Medicine; Research; Research Proposals; scaffold; scale up; Site; Small Business Innovation Research Grant; sound frequency; Stem cells; Stream; Suspensions; System; Technology; Temperature; Testing; Therapeutic; Time; Tissue Engineering; Tissues; Translating; Ultrasonography; Vacuum; Vision

This Small Business Innovation Research Phase II project will develop a commercially-viable device that uses micro-scale acoustic streaming (low frequency sound energy) to deliver mixing to the interior of three-dimensional (3D) scaffolds used for stem cell cultivation applications. The enabling advantage of low frequency sound energy is the ability to generate micro-scale mixing in and around scaffolds that can enhance the movement of liquid, molecules, and oxygen within scaffolds without the need for pumps or a costly and inconvenient perfusion apparatus for each scaffold. Preliminary data shows that cells can successfully grow in the presence of the acoustic energy field. Nutrient supply issues and difficulties in homogenously seeding dense scaffolds are issues that need to be overcome in order to successfully produce high quality, repeatable cell cultures in the complex 3D environments that are the mainstay of modern stem cell and tissue engineering. Many possible solutions to these problems have been examined, including the use of spinner flask, centrifugal, vacuum fixtures, or perfusion for cell seeding. The vision for the approach proposed here is to develop a single bioreactor platform on which multiple scaffolds can be mounted in simple fixtures to deliver similar benefits as those derived from complex perfusion bioreactors but without the significant time and capital investment inherent in such an approach. When used at low intensities, the proposed device should be able to deliver benefits similar to a perfusion bioreactor, but in a much simpler package. When used at higher intensities in the absence of cells, additional applications and benefits of the proposed product will be delivered in the form of much more rapid methods for the hydration, functionalization, and enzymatic degradation of scaffolds. The goal of this research proposal is to build a commercial prototype Acoustic Scaffold Bioreactor device and to extensively characterize and optimize its use for scaffold-based hematopoietic and mesenchymal stem cell culture systems. The commercial applications of the device will be broad within the field of stem cell and tissue engineering, extending to the full range of cells and tissues that have shown to be enhanced by more cumbersome perfusion flow-based systems, as well as to basic operations such as hydrating, functionalizing, and digesting scaffolds.

Public Health Relevance Statement:
This Small Business Innovation Research Phase II project will develop and demonstrate an Acoustic Scaffold Bioreactor (ASB) that employs a novel agitation method in the form of low-frequency sound energy. By greatly enhancing the penetration of liquids, molecules, and cells into the very small pores of natural and artificial scaffolds used for stem cell cultivation applications, the ASB will provide a low-cost, easy-to-use method of enhancing cellular growth and seeding within scaffolds. Better culture performance and cost-savings without the use of complex pumps and tubing will translate to more affordable stem cell-derived therapeutic products and better patient outcomes.

NIH Spending Category:
Bioengineering; Biotechnology; Regenerative Medicine; Stem Cell Research; Stem Cell Research - Nonembryonic - Human

Project Terms:
3-Dimensional; Acoustics; Adherent Culture; Agitation; base; Biocompatible Materials; Bioreactors; Biotechnology; Capital; Carbon Dioxide; Cell Culture System; Cell Culture Techniques; cell growth; cell injury; Cell Line; cell type; Cells; cellular engineering; commercial application; Complex; cost; Cost Savings; Cultured Cells; Data; design; design and construction; Development; Devices; Dimensions; Environment; Evaluation; exhaustion; flasks; Frequencies; Future; Goals; Growth; Guidelines; Hematopoietic; Hematopoietic stem cells; High temperature of physical object; Humidity; Hydration status; improved; Industrialization; Infusion Pumps; Investments; Laboratories; Liquid substance; Mesenchymal Stem Cells; Methods; Modeling; Modernization; Movement; new technology; novel; novel strategies; Nutrient; operation; Oxygen; Patient-Focused Outcomes; Penetration; Performance; Perfusion; Phase; Process; Productivity; Protocols documentation; prototype; Pump; rapid technique; Regenerative Medicine; Research; Research Proposals; scaffold; scale up; Site; Small Business Innovation Research Grant; sound frequency; Stem cells; Stream; Suspensions; System; Technology; Temperature; Testing; Therapeutic; Time; Tissue Engineering; Tissues; Translating; Ultrasonography; Vacuum; Vision