Biomimetic Tympanic Membrane Prosthesis Using Magnetic Bioreactor

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current materials for repairing or reconstructing the tympanic membrane, such as autologous and synthetic materials, face limitations in availability, success rate, and complications like fibrosis, and fail to adequately replicate the complex structure and function of the native membrane, especially for large perforations or non-traumatic lesions.

Innovation Solution

An apparatus and process for in vitro preparation of a biomimetic tissue prosthesis using mesenchymal stem cells, which replicates the characteristics of the tympanic membrane's intermediate connective layer, employing a bioreactor with magnetic stimuli to mimic mechanical conditions and promote collagen fiber organization, and a biocompatible support for cellular differentiation and growth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If autologous temporal fascia is used for myringoplasty, then the success rate of perforation closure is improved (88-95%), but the availability is limited by donor site constraints and the size of the lesion to be treated

Engineering Contradiction:
Improvesuccess rate of perforation closureVSAvoidavailability for large perforations
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention creates an artificial tympanic membrane that copies the structure and function of the native membrane. The prosthesis replicates the three-layer structure (epithelium, connective tissue, and basement membrane) and can be customized to match the specific defect size and location, overcoming the limitations of donor site availability while maintaining high success rates

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The invention allows customization of the prosthesis parameters including size, shape, and thickness to match the specific defect characteristics. This enables the use of standardized fabrication processes while adapting the final product to various defect sizes and locations, thereby improving versatility without compromising reliability

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If synthetic biomaterials are used for tympanic membrane replacement, then the availability is improved, but the materials suffer from rapid degradation and can lead to fibrosis of the middle ear

Engineering Contradiction:
Improveavailability of replacement materialsVSAvoiddegradation resistance and fibrosis prevention
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The invention uses a composite structure with a biocompatible support framework (such as collagen or synthetic biodegradable polymer) combined with living cells. This composite approach provides both the availability of synthetic materials and the reliability of biological tissues, as the living cells continue to produce extracellular matrix and remodel the tissue, preventing degradation and fibrosis

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The prosthesis employs different materials with specific properties in different regions: a biocompatible support structure for structural integrity and cell attachment, and a cellularized tissue layer for functional performance. This local differentiation allows each region to perform its specific function optimally while working together to prevent degradation and fibrosis

Inventive Principle:
Principle #3Local quality

3Adaptability or versatility

If homologous or heterologous transplants are used, then the availability of replacement material is improved, but the risk of infective disease transmission and rejection increases

Engineering Contradiction:
Improveavailability of replacement materialVSAvoidinfective disease transmission and rejection risk
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The invention uses the patient's own cells (autologous cells) to create the prosthesis, which then self-organize and self-renew in vitro before implantation. This eliminates the need for donor materials and the associated risks of infection and rejection, while maintaining high availability since the patient's own cells are always available

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention introduces a biocompatible support framework as an intermediary that provides structural support during the tissue engineering process and gradually degrades as the native tissue regenerates. This intermediary structure facilitates tissue formation without introducing foreign materials that could cause rejection or infection

Inventive Principle:
Principle #24Intermediary (Mediator)

4Reliability

If complex tissue engineering processes are used to create biomimetic structures, then the functional characteristics are improved, but the manufacturing complexity and time increase

Engineering Contradiction:
Improvefunctional characteristics of native membraneVSAvoidmanufacturing process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention performs preliminary actions by pre-seeding the support framework with cells and pre-culturing the tissue construct in a bioreactor before implantation. This allows the tissue to develop the desired complex structure and function in a controlled environment, simplifying the actual surgical implantation process and reducing overall treatment time

Inventive Principle:
Principle #10Preliminary action

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 resulting tissue prosthesis maintains the functional characteristics of the native membrane, including correct sound wave transmission, with improved success rates and reduced morbidity, as it closely mimics the anatomy and physiology of the tympanic membrane.

Implementation Method 1

said first magnetic means being arranged inside said tube and said second magnetic means being arranged outside said tube, said first and second magnetic means being movable relative to one another and being able to impart movements, and therefore mechanical stimuli, to the cellular culture arranged inside said tube

Methodology Applied
Scientific EffectMagnetic force: Magnetism

Data Source

PatentEP3047016B1Apparatus and process for the preparation of a biomimetic tissue prosthesis of the tympanic membrane
Publication Date: 2021.01.13 AZIENDA OSPEDALIERO UNIVRIA PISANA
  • EP3047016B1 patent drawingFigure 1~2
  • EP3047016B1 patent drawingFigure 3~4
  • EP3047016B1 patent drawingFigure 5(A)~6(C')

AI summary

The present invention refers to a process, and to the related apparatus, for the in vitro preparation of a biomimetic tissue prostheses of the tympanic membrane from mesenchymal stem cells; such prostheses are used for repairing or reconstructing the injured tympanic membrane in patients needing it, for example as a consequence of various trauma or pathologies.