Multilayered Cell Sheet with Vascular Network via Artery-Vein Loop
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Solution Overview
Problem
Conventional methods for culturing multilayered cell sheets are limited by the inability to infinitely layer cells, leading to structural defects and requiring repeated transplantation, which is burdensome for recipients.
Innovation Solution
A method involving the construction of a vascular bed with an artery-vein loop and capillary network, allowing cell sheets to be layered and perfused with culture medium in vitro to create thick, vascularized cell sheets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If conventional methods are used to culture multilayered cell sheets, then cell sheets can be cultured on substrate surfaces, but the sheets cannot be infinitely layered and are limited to about three layers due to structural defects
Solution Approach 1:
The invention divides the cell sheet production process into multiple independent layers that can be cultured separately and then stacked. Each layer is cultured on its own substrate surface, allowing independent optimization of each layer's quality, thereby enabling thick multilayered structures without compromising structural integrity
Solution Approach 2:
The invention transitions from culturing cells in a single plane to constructing three-dimensional multilayered structures by stacking multiple two-dimensional cell sheets vertically. This dimensional transition enables thick cell sheet production while maintaining the structural precision of each individual layer
2Quantity of substance
If cell sheets are layered multiple times to increase thickness, then more cells can be produced, but repeated transplantation is required which is burdensome for recipients
Solution Approach 1:
The invention performs preliminary layering of multiple cell sheets during the in vitro culturing phase, constructing the complete multilayered structure before transplantation. This preliminary construction eliminates the need for repeated surgical procedures to add layers, reducing the burden on recipients while achieving the desired cell quantity
3Volume of stationary object
If cell sheets are layered to increase thickness, then more tissue can be produced, but vascular networks are required to supply nutrients and oxygen to each layer
Solution Approach 1:
The invention embeds vascular networks within the multilayered cell sheet structure, with blood vessels extending into each layer to deliver nutrients and oxygen. This nested arrangement allows thick tissue volume to be sustained by integrating the vascular system directly into the hierarchical structure of the cell sheets
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 production of thick, layered cell sheets with a vascular network, facilitating regenerative medicine and drug evaluation while reducing the need for repeated transplantation and minimizing individual animal variability.
Implementation Method 1
the surface of the substrate is coated with a polymer having an upper or lower critical solution temperature of 0 to 80° C. in water, the cells are cultured at a temperature not exceeding the upper critical solution temperature or not failing below the lower critical solution temperature, and the cultured cells are detached by increasing or decreasing the temperature of the substrate to exceed the upper critical solution temperature or fall below the lower critical solution temperature
Data Source
AI summary
A method for producing multilayered cell sheets, including producing a vascular bed which includes an artery-vein loop and in which a capillary vascular network is constructed; layering cell sheets on the vascular bed; and perfusing a culture medium in vitro to construct a vascular network in the cell sheets. The production method enables vascular networks to be constructed in cell sheets and enables thick multilayered cell sheets to foe easily produced by layering the cell sheets. Such thick multilayered cell sheets are useful as in vivo tissue-like products for regenerative medicine for various tissues and for evaluation of drugs and the like.