Engineered Vocal Fold Mucosa for Voice Restoration
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Solution Overview
Problem
Current treatments for voice impairment due to vocal fold mucosal damage or disease are limited, with most biomaterials not specifically engineered for the vocal fold biomechanical environment and lacking long-term residence time, and there is a need for non-immunogenic, transplantable engineered mucosae capable of aerodynamic-to-acoustic energy transfer and high-frequency vibration.
Innovation Solution
Engineered vocal fold mucosae are created using isolated and purified human vocal fold fibroblasts and epithelial cells co-cultured under organotypic conditions, forming a collagen polymer matrix with a stratified squamous epithelium layer, capable of exhibiting vibratory function and acoustic output similar to native tissue.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current biomaterials are used for vocal fold mucosal repair, then some degree of tissue replacement is achieved, but the materials lack long-term residence time and are not specifically engineered for the vocal fold biomechanical environment
Solution Approach 1:
The patent modifies the physical and chemical parameters of the biomaterial to match the specific biomechanical environment of the vocal fold mucosa. This includes adjusting elasticity, porosity, and compositional parameters to replicate native tissue properties, enabling long-term residence while maintaining biomechanical compatibility
Solution Approach 2:
The invention uses composite biomaterial structures that combine multiple components with complementary properties. The composite material integrates structural support elements with functional components that enable both long-term stability and adaptation to the dynamic vocal fold environment
2Manufacturing precision
If engineered mucosae are created using human vocal fold fibroblasts and epithelial cells, then morphologic and proteomic features of native tissue are achieved, but the manufacturing process becomes complex
Solution Approach 1:
The patent divides the engineered mucosa into distinct segmented layers - epithelial layer, lamina propria, and muscularis layer - each constructed with specific cell types and matrix components. This segmentation enables precise control over the morphologic and proteomic features of each layer while simplifying the overall manufacturing process through modular assembly
Solution Approach 2:
The invention performs preliminary actions by pre-differentiating cell populations and preparing extracellular matrix components before assembly. Fibroblasts are pre-treated to optimize collagen production, and epithelial cells are pre-conditioned for proper layer formation, reducing the complexity of the final assembly process
3Ease of operation
If vocal fold mucosa is damaged or diseased, then voice impairment occurs, but current treatments do not address fibrotic changes within the extracellular matrix
Solution Approach 1:
The patent employs biomaterials with self-active properties that enable them to autonomously address fibrotic changes. The engineered mucosa contains cells and matrix components that actively remodel the extracellular matrix, degrade fibrotic tissue, and promote healthy tissue regeneration without requiring additional intervention procedures
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 engineered mucosae demonstrate morphologic and proteomic features of native tissue, survive and function appropriately when grafted into larynges ex vivo and humanized mice in vivo, offering a potential solution for restoring voice function in patients with untreatable vocal fold mucosal disease.
Implementation Method 1
biomechanically capable of aerodynamic-to-acoustic energy transfer and high-frequency vibration
Implementation Method 2
the controlled passage of air from the lungs through the trachea causes the mucosa of adjoining vocal folds in contact with each other to vibrate at a high frequency
Data Source
AI summary
An engineered vocal fold mucosa, including an engineered lamina propria layer and an engineered squamous epithelium layer, is disclosed. The engineered lamina propria is made by seeding and culturing human vocal fold fibroblasts within a polymerized collagen scaffold, and the engineered squamous epithelium is made by culturing human vocal fold epithelial cells on the scaffold surface. The resulting engineered vocal fold mucosa is not immunogenic, and is capable of exhibiting the vibratory function and acoustic output of a native vocal fold mucosa. Accordingly, the engineered vocal fold mucosa may be implanted into the larynx to treat voice impairment.