Methods of extruding multilayer fibers
Patent Number: WO2016172707
Executive Summary:
General Description:
Tumor progression, invasion, and metastasis are regulated by signaling events between multiple cell types. It is essential to accurately model these interactions in vitro for basic studies and for drug screening; however, current systems fall short of mimicking the complex organization of cells and matrix in vivo. Microfluidic devices provide a means to organize 3D microenvironments such as cysts and tubules, which mimic the basic building blocks of epithelial tissue. It has been a challenge to develop a multilayer medium for maintenance and growth of cultured cells in which intracellular interactions can be observed and measured, particularly in a context that resembles blood vessels and the surrounding tissue: a solid or semi-solid matrix surrounding a vessel through which liquid can flow.
This invention describes a method to produce multi-layer tubules, in which the outer layer is a hydrogel, and the inner layer is a cell growth medium. It demonstrates a versatile approach to multi-domain tissue mimetics by extruding multilayer fibers under controlled flow rates that create folded, hierarchically conformed and/or overlapping fibrous masses representative of natural tissue. Macrophages and breast adenocarcinoma cells were seeded to different concentric layers of the microfiber to create a model of a paracrine loop that regulates metastasis. Effects of clinical drug treatments and observation of a dose-dependent modulation of cellular migration can be performed in this system. This versatile and tunable approach for tissue fabrication represents a means to study a wide range of microenvironments and may provide a clinically-viable solution for personalized assessment of patient response to therapeutics.
Future Directions:
Strengths:
Patent Status:
Publications:
Grolman JM, Zhang D, Smith AM, Moore JS, Kilian KA. Rapid 3D Extrusion of Synthetic Tumor Microenvironments. Adv Mater. 2015 Oct 7;27(37):5512-7. doi:10.1002/adma.201501729. Epub 2015 Aug 18. PubMed PMID: 26283579; PubMed Central PMCID: PMC4745120.
Inventor Bio: Joshua M. Grolman
https://mooneylab.seas.harvard.edu/people/joshua-m-grolma
Executive Summary:
- Invention Type: Device
- Patent Status: Patent pending
- Patent Link: https://patents.google.com/patent/WO2016172707
- Research Institute: University of Illinois
- Disease Focus: Cancer
- Basis of Invention: Microfluidic device designed to create multi-layer tubes of different shapes with a more solid outer layer and a liquid inner layer
- How it works: The microtubes form a matrix in which cells are cultured in the conditions closely resembling the microenvironment existing in vivo
- Lead Challenge Inventor: Joshua M. Grolman
- Inventors: Joshua M. Grolman
- Development Stage: validated in vitro using breast cancer cells and macrophages
- Novelty:
- Extrusion of multi-layered microfibers of defined sizes, shapes and composition
- Modeling the tumor cell interactions with blood vessels and macrophages
- Clinical Applications:
- Drug discovery
- Personalized assessment of therapy efficiency using the patient-derived cells
General Description:
Tumor progression, invasion, and metastasis are regulated by signaling events between multiple cell types. It is essential to accurately model these interactions in vitro for basic studies and for drug screening; however, current systems fall short of mimicking the complex organization of cells and matrix in vivo. Microfluidic devices provide a means to organize 3D microenvironments such as cysts and tubules, which mimic the basic building blocks of epithelial tissue. It has been a challenge to develop a multilayer medium for maintenance and growth of cultured cells in which intracellular interactions can be observed and measured, particularly in a context that resembles blood vessels and the surrounding tissue: a solid or semi-solid matrix surrounding a vessel through which liquid can flow.
This invention describes a method to produce multi-layer tubules, in which the outer layer is a hydrogel, and the inner layer is a cell growth medium. It demonstrates a versatile approach to multi-domain tissue mimetics by extruding multilayer fibers under controlled flow rates that create folded, hierarchically conformed and/or overlapping fibrous masses representative of natural tissue. Macrophages and breast adenocarcinoma cells were seeded to different concentric layers of the microfiber to create a model of a paracrine loop that regulates metastasis. Effects of clinical drug treatments and observation of a dose-dependent modulation of cellular migration can be performed in this system. This versatile and tunable approach for tissue fabrication represents a means to study a wide range of microenvironments and may provide a clinically-viable solution for personalized assessment of patient response to therapeutics.
Future Directions:
- Development of the technology with patient-derived cells
Strengths:
- Clever and relatively simple device to produce 3D structures populated with a variety of cell types
Patent Status:
- Filing date: 2016-04-25
- Publication date: 2016-10-27
Publications:
Grolman JM, Zhang D, Smith AM, Moore JS, Kilian KA. Rapid 3D Extrusion of Synthetic Tumor Microenvironments. Adv Mater. 2015 Oct 7;27(37):5512-7. doi:10.1002/adma.201501729. Epub 2015 Aug 18. PubMed PMID: 26283579; PubMed Central PMCID: PMC4745120.
Inventor Bio: Joshua M. Grolman
https://mooneylab.seas.harvard.edu/people/joshua-m-grolma