Using computer-aided tissue engineering system for use in generation of matrices for propagating preferential tissues; tissue engineering and repair regenerative medicine
Inventors
Gonda, Steve R. • VON GUSTEDT-GONDA, LEGAL REPRESENTATIVE IRIS, null • Chang, Robert C. • Starly, Binil • Culbertson, Christopher • Holtorf, Heidi L. • Sun, Wei • Leslie, Julia
Assignees
National Aeronautics and Space Administration NASA
Publication Number
US-8343740-B2
Publication Date
2013-01-01
Expiration Date
2028-03-28
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Abstract
A method for fabricating a micro-organ device comprises providing a microscale support having one or more microfluidic channels and one or more micro-chambers for housing a micro-organ and printing a micro-organ on the microscale support using a cell suspension in a syringe controlled by a computer-aided tissue engineering system, wherein the cell suspension comprises cells suspended in a solution containing a material that functions as a three-dimensional scaffold. The printing is performed with the computer-aided tissue engineering system according to a particular pattern. The micro-organ device comprises at least one micro-chamber each housing a micro-organ; and at least one microfluidic channel connected to the micro-chamber, wherein the micro-organ comprises cells arranged in a configuration that includes microscale spacing between portions of the cells to facilitate diffusion exchange between the cells and a medium supplied from the at least one microfluidic channel.
Core Innovation
Embodiments of the present invention relate to methods for fabricating micro-organ devices by providing a microscale support comprising one or more microfluidic channels and micro-chambers for housing micro-organs, and printing micro-organs on the microscale support using a cell suspension controlled by a computer-aided tissue engineering (CATE) system. The cell suspension comprises cells suspended in a solution that functions as a three-dimensional scaffold, and the printing is performed according to a particular pattern.
The invention addresses the problem that existing in vitro testing systems for pharmaceuticals and biological compounds do not accurately replicate the in vivo physiological conditions, leading to difficulties in predicting human responses. Traditional cell culture methods lack proper cell-cell communication and interactions, and the related art systems, including multi-compartmental and microscale devices, do not always provide reproducible organs or sufficiently mimic in vivo functions.
The micro-organ devices (MODs) fabricated by the disclosed methods comprise three-dimensional tissue analogs formed by bioprinting cells with extracellular matrices and scaffolding directly onto microchips, which include microfluidic channels and micro-chambers. These MODs mimic multiple organ interactions and enable fluid diffusion and exchange between cells and media. The invention enables constructing arrays of micro-organs arranged according to in vivo tissue architecture and fluid conditions to better simulate metabolism, pharmacokinetics, and tissue interactions.
Claims Coverage
The patent contains one independent claim covering the method for fabricating a micro-organ device with specific inventive features.
Fabrication of a microscale support with microfluidic channels and micro-chambers
The method includes providing a microscale support comprising at least one microfluidic channel and at least one micro-chamber designed for housing a micro-organ.
Bonding microscale support to a substrate using titanium tetra(isopropoxide)
The microscale support is bonded to a substrate by covering the contact surfaces of each with titanium tetra(isopropoxide), facilitating assembly of the micro-organ device.
Printing of micro-organs using computer-aided tissue engineering system
Micro-organs are printed onto the microscale support using a cell suspension contained in a syringe controlled by a computer-aided tissue engineering (CATE) system, allowing precise deposition of cells.
Use of a cell suspension with three-dimensional scaffold material
The cell suspension used for printing comprises cells suspended in a solution containing a material that functions as a three-dimensional scaffold, enabling structural support to the printed micro-organ.
Printing performed according to a particular pattern
The printing process is performed with the CATE system according to a particular pattern, enabling the creation of micro-organs with designed spatial configurations for effective diffusion and tissue modeling.
The independent claim recites a method integrating microscale supports with microfluidic features, bonding techniques, and precise bioprinting of cell suspensions containing scaffold materials using computer-aided systems to fabricate reproducible micro-organ devices with defined architectures for improved tissue modeling.
Stated Advantages
Biopatterning and bioprinting of cells, extracellular matrices, and scaffolding directly on microfluidic microchips enable precise spatial control and reproducibility of micro-organ fabrication.
The methods minimize variations in local cell seeding densities and selection pressures favoring aggressive cells, improving consistency in organ models.
Direct bioprinting allows precise and simultaneous coupling of multiple microfluidic channels on one microchip with those on another, facilitating complex multi-organ interactions.
The methods enable control of volumetric and quantitative accuracy suitable for pharmacodynamics, pharmacokinetics, and toxicity studies.
Micro-organ devices mimic in vivo circulation profiles within and between organs and can be automated, have minimal footprints and power requirements, use micro-volumes of fluids, generate minimal waste, and provide high throughput and parallel analyses.
Micro-organ devices require minimal resources for toxicology and pharmacological investigations and have high extrapolation potential to animal or human studies, reducing reliance on animal testing and potentially improving drug candidate selection.
Documented Applications
Experimental pharmaceutical screening for efficacy, absorption, distribution, metabolism, elimination, and toxicity using micro-organ devices that mimic human or animal organs.
Assessment of therapeutic or toxic effects of drugs on target organs or cell types within a micro-organ device environment including liver-dependent metabolic modifications.
Pharmacokinetic and pharmacodynamic studies using micro-organ devices comprising multiple interconnected micro-organs to study organ interactions and metabolite effects.
Use in drug metabolism studies, including enzyme activity assays such as liver cytochrome P450-mediated conversions.
Potential use in space and terrestrial environments as drug screening systems with human cell micro-organs to supplement or reduce animal studies.
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