Layered Cell Sheets with Controlled Myoblast Orientation
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Solution Overview
Problem
Current methods fail to control the alignment of myoblasts in three-dimensional structures, limiting the design of muscle tissue mimicking the body's organization, and existing cell sheet technologies do not allow for the separation of myoblasts from processed surfaces, hindering the creation of oriented myotube constructs.
Innovation Solution
The development of layered cell sheets with controlled orientations of myoblasts, achieved by culturing myoblasts on a thermoresponsive polymer-coated substrate and detaching them to maintain alignment, allowing for the layering of sheets with identical orientations, including vascular endothelial cells or nerve cells, to create aligned myotube constructs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If myoblasts are cultured on finely processed materials to control alignment, then cell orientation is improved, but separation of myoblasts from the surface becomes impossible
Solution Approach 1:
A thermoresponsive polymer layer is introduced as an intermediary between the substrate and myoblasts. This polymer enables controlled cell alignment through its thermal properties while allowing easy separation by temperature change, resolving the contradiction between alignment control and separation ease
Solution Approach 2:
The patent utilizes temperature as a controllable parameter to change the properties of the thermoresponsive polymer. By changing temperature, the polymer transitions between states that favor cell adhesion/alignment and states that enable easy cell separation, thus resolving the contradiction
2Volume of moving object
If conventional cell sheet layering is used, then tissue thickness is improved, but control of cell orientation in three dimensions is lost
Solution Approach 1:
The patent extends the alignment control from two-dimensional surfaces to three-dimensional layered structures by using thermoresponsive polymers on each layer. This enables maintained orientation control as layers are stacked, resolving the contradiction between tissue thickness and orientation precision
3Reliability
If additional procedures such as suture are used for transplantation, then cell sheet attachment is improved, but the procedure complexity increases
Solution Approach 1:
The thermoresponsive polymer-coated cell sheets possess self-adhesive properties that enable direct attachment to target tissues without requiring additional procedures like sutures. The polymer's thermal properties facilitate both easy harvesting and reliable transplantation, reducing procedure 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
This approach enables the efficient formation of uniformly oriented myotubes, facilitating muscle tissue regeneration with controlled orientations, enabling efficient engraftment and functional recovery of damaged sites in regenerative medicine.
Implementation Method 1
Poly(N-isopropylacrylamide) (PIPAAm) which is a thermoresponsive polymer grafted on a cell culture substrate has enabled confluent cells to be harvested without being damaged as a single cell sheet at a culture temperature allowed to be lower than 32°C which is the lower critical solution temperature (LCST) of PIPAAm
Data Source
Figure 1a~2d
Figure 3a~4b
Figure 5a~6e
AI summary
Provided are layered cell sheets, comprising a plurality of layered cell sheets containing myoblasts, in which each cell sheet comprises cell population containing myoblasts with controlled orientations. Preferably provided are the layered cell sheets comprising a region in which the orientations of the cell population containing the myoblasts in each cell sheet are identical to each other.