Multilayer Engineered Heart Muscle With Oxygen Diffusion Channels
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Solution Overview
Problem
Existing engineered heart muscle designs struggle to achieve adequate thickness and oxygen/nutrient supply for cells, limiting their effectiveness in supporting heart function.
Innovation Solution
A method involving repetitive and sequential layering of a cell-containing hydrogel with perforated poles to create a multilayer engineered heart muscle (MEHM), ensuring minimal diffusion distance and nutrient/oxygen supply through channels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If the engineered heart muscle is made thicker to support human heart function, then the mechanical strength and support capability are improved, but the oxygen and nutrient supply to cells deteriorates due to increased diffusion distance
Solution Approach 1:
The engineered heart muscle is divided into multiple thin layers stacked together, with each layer containing poles that create channels for nutrient and oxygen distribution. This segmentation allows the tissue to achieve greater overall thickness while maintaining short diffusion distances within each layer, resolving the contradiction between mechanical strength and nutrient supply.
Solution Approach 2:
The invention transitions from a single-layer thick tissue to a multilayer structure, adding the dimension of layering. By distributing the thickness across multiple layers with internal channels, the design achieves both sufficient mechanical strength and adequate nutrient diffusion pathways.
2Device complexity
If a single thick layer of engineered heart muscle is created, then the structural simplicity is maintained, but the oxygen and nutrient supply to the core cells deteriorates
Solution Approach 1:
The single thick layer is segmented into multiple thinner layers stacked together. Each layer contains poles that create channels, ensuring that no cell is more than a short diffusion distance from a nutrient or oxygen source, thereby preventing core cell hypoxia while maintaining structural organization.
Solution Approach 2:
The engineered heart muscle incorporates poles throughout the tissue structure that create porous channels for nutrient and oxygen distribution. This porous architecture ensures adequate supply to all cells regardless of their position in the multilayer structure.
3Adaptability or versatility
If the engineered heart muscle is made thicker to match human heart wall thickness, then the applicability for implantation is improved, but the manufacturing complexity increases due to diffusion constraints
Solution Approach 1:
The manufacturing process is simplified by segmenting the thick tissue into multiple thin layers that can be independently formed and then stacked. Each layer is easier to manufacture with proper nutrient diffusion, and the stacking process creates the final thick implant structure, making the overall manufacturing more manageable despite the increased number of steps.
Solution Approach 2:
The invention uses layering in the third dimension to achieve the required implant thickness. By stacking multiple thin layers with embedded poles, the process achieves human-heart-appropriate thickness while maintaining manufacturability through standardized layer formation and assembly 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 MEHM maintains sufficient oxygen and nutrient supply to cells, enabling the production of a thick, contractile heart muscle suitable for implantation, mimicking natural heart function.
Implementation Method 1
a reconstitution mixture comprising (a) collagen, (b) a cellular mixture of cardiac myocytes and non-myocytes and (c) a suitable reconstitution medium, whereby said reconstitution mixture undergoes gelation in the mould
Implementation Method 2
the engineered heart muscle is penetrated by a mechanical support, wherein poles extend through the engineered tissue in order to support auxotonic contractions and introduce channels for oxygen and nutrient supply throughout the engineered tissue
Implementation Method 3
Mechanical loading is an absolute requirement for the engineering of heart muscle with advanced maturation
Data Source
AI summary
A method for manufacturing a multilayer engineered heart muscle that includes (i) providing a liquid reconstitution mixture in a mould and (ii) culturing the mixture. The method includes a sequential addition of one or more further liquid reconstitution mixtures to obtain a multilayer engineered heart muscle. The muscle ideally has the form of a patch, a pouch, or a cylinder. Furthermore, a multilayer engineered heart muscle having collagen, cardiac myocytes and non-myocytes originating from at least 2 layers is disclosed. The multilayer engineered heart muscle forms the basis for several in vitro and in vivo applications such as the production of a multilayer engineered heart muscle for use in a patient, for example for use in heart repair.