Multiring Engineered Heart Tissue Fusion
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Solution Overview
Problem
Current cardiac tissue engineering approaches fail to produce large, functional heart tissue grafts with sufficient contractile strength and vascularization for effective heart tissue augmentation or replacement, as they are limited by nutrient and oxygen diffusion, and lack structural and electrical integration with the host myocardium.
Innovation Solution
The method involves fusing multiple force-generating engineered heart tissue rings to form a multiring construct, which allows for larger tissue constructs that can be tailored for therapeutic use, maintaining accessibility for nutrient exchange and exhibiting enhanced contractile properties through culturing and tensile stress application.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If multiple engineered heart tissue rings are fused to form larger constructs, then the contractile strength and functional support for failing hearts is improved, but the complexity of the tissue construction and culturing process increases
Solution Approach 1:
The invention divides the large tissue construct into multiple smaller engineered heart tissue rings that can be individually cultured and then fused together. Each ring serves as a manageable unit that maintains accessibility for nutrient exchange while contributing to the overall contractile strength when combined with other rings in a multiring construct.
Solution Approach 2:
The invention combines multiple individually cultured engineered heart tissue rings into a fused multiring construct. This merging process allows the individual rings to work together synergistically, providing enhanced contractile strength and functional support for failing hearts while maintaining the advantages of modular construction.
2Quantity of substance
If larger tissue constructs are engineered to provide sufficient support for heart replacement, then the functional capacity is improved, but the nutrient and oxygen diffusion becomes insufficient
Solution Approach 1:
The invention segments the large tissue construct into multiple smaller rings, each with dimensions that allow adequate nutrient and oxygen diffusion. By maintaining the small size of individual rings while creating a larger overall construct through fusion, the invention ensures that no region is too far from the surface for effective diffusion while still providing sufficient total tissue mass for functional heart support.
Solution Approach 2:
The multiring construct can be configured with rings arranged in nested or stacked configurations, where multiple smaller functional units are organized to form a larger structure. This nesting approach allows each small ring to maintain its diffusion efficiency while the collective arrangement provides the necessary scale for heart replacement applications.
3Manufacturing precision
If engineered heart tissue is designed to match the size and contractile features of native heart tissue, then the therapeutic effectiveness is improved, but the metabolic supply becomes insufficient
Solution Approach 1:
The invention creates a multiring construct composed of multiple smaller rings, each with dimensions optimized for adequate metabolic supply through diffusion. By arranging these smaller rings in a fused configuration, the overall construct achieves the size and contractile features necessary for therapeutic effectiveness while each individual ring maintains its metabolic viability.
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 multiring engineered heart tissue constructs demonstrate improved contractile strength and vascularization, enabling effective support for failing hearts and potential use in cardiac tissue augmentation and drug screening assays, with the ability to be derived from human cells for human therapy.
Implementation Method 1
placing into contact at least two force-generating engineered heart tissue rings so that each force-generating engineered heart tissue ring has one or more contact points to an adjacent force-generating engineered heart tissue ring; and culturing the force-generating engineered heart tissue rings under conditions which allow fusion of the at least two force-generating engineered heart tissue rings at the one or more contact points
Data Source
AI summary
The invention is directed to a method for the preparation of a multiring engineered heart tissue construct suitable for use in cardiac tissue augmentation and/or replacement therapy. The invention further refers to multiring EHT constructs which comprise at least two force-generating engineered heart tissue rings fused with each other and a device for preparing the same. Finally, the invention relates to force-generating engineered heart tissue rings derived from human cells and their use in drug screening and target validation assays.