Funnel-Guide Microtissue Stacking for High-Density Tissue Constructs
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Solution Overview
Problem
Current tissue engineering methods face challenges in creating large, thick tissue constructs with high cell densities due to limitations in oxygen, nutrient, and waste diffusion, and existing bio-printers struggle to produce complex structures with sufficient cell density and throughput.
Innovation Solution
A funnel-guide device and method for assembling adherent cells, allowing for non-contact manipulation and positioning of multi-cellular microtissues layer-by-layer, using a funnel-guide device with a free fall chamber, funnel chamber, and stacking chamber to form macrotissues, enabling precise placement and perfusion of cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If bio-printers are used to fabricate tissue structures, then structures can be printed layer-by-layer, but the cell density is insufficient and throughput is slow
Solution Approach 1:
The invention segments the tissue fabrication process into two distinct stages: (1) pre-assembly of high-density cell aggregates (microtissues) using agitation-based methods, and (2) layer-by-layer stacking of these pre-formed aggregates using the funnel-guide device. This segmentation allows each stage to be optimized independently, achieving both high cell density in the aggregates and precise structural control in the final assembly.
Solution Approach 2:
The invention performs preliminary action by pre-forming high-density cell aggregates (microtissues) before the final assembly step. These pre-assembled microtissues contain high cell densities (10^8-10^9 cells/mL) that are achieved through agitation-based aggregation methods, which would be impossible to achieve through direct bio-printing. The pre-formed aggregates are then stacked using the funnel-guide device to create the final tissue structure.
2Volume of moving object
If tissue thickness is increased to match natural organs, then more cells can be contained, but diffusion of oxygen and nutrients becomes insufficient
Solution Approach 1:
The invention segments thick tissue constructs into stacks of thinner microtissue layers, each with sufficient diffusion characteristics for cell viability. By stacking multiple high-density cell aggregates in a layer-by-layer manner, the invention creates thick overall structures while maintaining thin individual layers that allow adequate diffusion of oxygen and nutrients to all cells.
3Manufacturing precision
If pick-and-place instruments are used to assemble cell aggregates, then precise positioning is achieved, but the instruments damage tissues and cannot operate in aqueous environment
Solution Approach 1:
The invention replaces contact-based mechanical pick-and-place instruments with a non-contact funnel-guide system that uses gravity and fluid dynamics to position microtissues. The funnel-guide device creates a controlled aqueous environment where microtissues self-assemble and stack through gravitational settling and fluid flow, eliminating mechanical contact that would damage the delicate cell aggregates.
Solution Approach 2:
The invention uses hydraulic principles by operating the entire assembly process in an aqueous environment (cell culture medium). The funnel-guide device utilizes fluid flow and gravitational settling in this aqueous medium to achieve precise positioning of microtissues without mechanical contact, replacing traditional pneumatic or mechanical pick-and-place systems that would damage the tissues.
4Reliability
If simple structures are printed with bio-printers, then fabrication is successful, but complex organ-like structures cannot be achieved
Solution Approach 1:
The invention segments complex organ-like structures into stacks of simpler microtissue layers. Each individual microtissue layer is relatively simple in structure and can be reliably fabricated with high success rates. The complexity arises from the precise stacking and arrangement of these simple layers into three-dimensional structures that mimic natural organs, achieving both reliability in individual layer fabrication and versatility in overall structural complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables the construction of large, three-dimensional tissue assemblies with high cell density, overcoming diffusion limitations and achieving complex structures that mimic natural tissues, with potential applications in tissue engineering and drug testing.
Implementation Method 1
a funnel-guide device with a free fall chamber, funnel chamber, and stacking chamber to form macrotissues
Implementation Method 2
enabling precise placement and perfusion of cells
Data Source
AI summary
The invention provides a device and a method for the assembly of an aggregation of adherent cells, particularly a three-dimensional assembly of adherent cells.