Temperature-Responsive Cell Sheet for Middle Ear Mucosa Regeneration
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Solution Overview
Problem
In middle ear surgeries, especially for cholesteatoma, preserving and regenerating mucosa on exposed bone surfaces is challenging, leading to re-adhesion of the eardrum and delayed mucosa conversion to epithelium, which affects gas exchange and cilia function, making it difficult to maintain the pneumatic space in the middle ear cavity.
Innovation Solution
A middle ear mucosa-like cell sheet is created by culturing nasal epithelium cells on a temperature-responsive polymer substrate, allowing the cells to be detached without protease treatment and engrafted onto the bone surface, inhibiting granulation tissue and fibroblast hyperplasia, and maintaining cilia function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nasal mucosa or oral mucosa transplantation is performed to regenerate mucosa on exposed bone surface, then mucosa regeneration is achieved, but suturing in the narrow middle ear cavity is difficult and the exposed bone surface is not appropriate as a scaffold
Solution Approach 1:
The patent creates a cell sheet that replicates the structure and function of native middle ear mucosa using nasal epithelium cells cultured on a temperature-responsive substrate. This cell sheet can be transplanted to regenerate mucosa on exposed bone surfaces without requiring traditional suturing techniques, as the cell sheet itself forms a functional barrier and scaffold.
Solution Approach 2:
The patent extracts and cultures nasal epithelium cells separately from the nasal mucosa tissue, then regenerates them into a cell sheet format. This allows the mucosal function to be separated from the original tissue source and applied to the middle ear cavity where it is needed, avoiding the complexity of suturing traditional mucosal flaps.
2Ease of manufacture
If protease treatment is used to detach cultured cells, then cell detachment is achieved, but cell damage occurs
Solution Approach 1:
The patent utilizes temperature-responsive polymers that change their physical properties in response to temperature changes. By adjusting the temperature parameter, the polymer substrate can be detached from the cell culture substrate without requiring protease treatment, thereby avoiding cell damage while achieving complete cell detachment.
3Productivity
If mucosa is not regenerated on exposed bone surface after surgery, then surgical procedure is simple, but re-adhesion of eardrum and reconstitutive cholesteatoma occur
Solution Approach 1:
The patent prepares nasal epithelium cells in advance and cultives them into a cell sheet format before the surgical procedure. This preliminary preparation allows the cell sheet to be ready for immediate transplantation during surgery, promoting rapid mucosa regeneration on exposed bone surfaces and preventing re-adhesion and reconstitutive cholesteatoma formation.
4Reliability
If mucosa conversion to epithelium is delayed after surgery, then gas exchange function and cilia function are lost, but obtaining mucosa from healthy tissue raises ethical problems
Solution Approach 1:
The patent creates a cell sheet that copies the functional characteristics of middle ear mucosa using nasal epithelium cells. These cells are cultured and maintained in vitro, preserving their gas exchange and cilia functions, then transplanted to regenerate the mucosa in the middle ear cavity, thereby avoiding the need to harvest from healthy tissue while maintaining functional integrity.
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
The cell sheet effectively substitutes lost mucosa, preventing re-adhesion and reconstitutive cholesteatoma, promoting ventilatory function and gas exchange, and can be used for treating middle ear conditions and other mucosal losses without ethical concerns related to healthy tissue procurement.
Implementation Method 1
a cell culture substrate coated with a polymer whose hydration force changes within a temperature range of 0 to 80°C
Data Source
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AI summary
The purpose of the present invention is to obtain an alternative to a substitute of the mucosa in the middle ear which is engrafted on the surface of the bone in the middle ear, hyperplasia of the granulation tissue and the bone and the development of the fibroblast cells in the middle ear are suppressed, and to obtain a middle ear mucosa-like cell sheet retaining cilia in the surface layer, comprising culturing nasal epithelium cells on a cell culture substrate coated with a polymer whose hydration force changes within a temperature range of 0 to 80°C, wherein the cells are cultured within a temperature range where the hydration force of the polymer is weak, and then changing the temperature to a temperature at which the hydration force is strong to recover the cultured cell sheet.