Decellularized Cardiac Matrix for Cell Retention
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Solution Overview
Problem
Current treatments for heart failure post-myocardial infarction, such as cellular transplantation, face challenges due to poor cell survival and retention in vivo, as existing matrices like fibrin, collagen, and matrigel fail to adequately mimic the native cardiac extracellular matrix, leading to limited regeneration and tissue repair.
Innovation Solution
A composition comprising decellularized extracellular matrix derived from cardiac or skeletal muscle tissue, which can be formulated into a injectable gel, mimicking the native tissue environment to recruit cells and deliver therapeutic agents, thereby enhancing cell survival and tissue regeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If naturally derived materials such as fibrin, collagen, alginate, matrigel, and gelatin are used for injection into the myocardium, then cell transplantation can be performed, but these materials fail to provide a significant amount of native components of the heart extracellular matrix, resulting in poor cell survival and limited tissue regeneration
Solution Approach 1:
The patent creates a decellularized extracellular matrix scaffold that copies the native cardiac extracellular matrix structure and composition. By removing cells from native heart tissue while preserving the extracellular matrix architecture, the invention provides a biomimetic scaffold that closely replicates the natural environment, thereby improving cell survival and tissue regeneration compared to conventional materials like fibrin or collagen alone
Solution Approach 2:
The decellularized extracellular matrix represents a composite material combining multiple native cardiac matrix components (collagens, elastins, glycosaminoglycans, and other proteins) in their natural ratios and spatial arrangements. This composite structure provides superior biochemical and biomechanical cues for cell attachment, proliferation, and differentiation compared to single-material approaches
2Productivity
If cells are injected into the left ventricle infarct wall to regenerate myocardium, then tissue regeneration is attempted, but injected cell survival is poor due to lack of proper matrix support
Solution Approach 1:
The patent prepares the extracellular matrix scaffold in advance by decellularizing native heart tissue to create a pre-formed, cell-ready matrix structure. This preliminary preparation ensures that when therapeutic cells are introduced, they immediately encounter a supportive matrix environment that promotes survival and integration, rather than being injected as bare cells into a non-supportive milieu
Solution Approach 2:
The decellularized extracellular matrix acts as an intermediary between the injected cells and the host tissue environment. This matrix scaffold mediates cell survival by providing adhesive ligands, structural support, and biochemical signals, while also mediating integration with surrounding native tissue, thereby enhancing the overall effectiveness of cell transplantation therapy
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 use of decellularized extracellular matrix as an in situ scaffold improves cell retention and survival, promoting myocardial and skeletal muscle tissue regeneration, and supporting cardiac function by providing a natural environment for cell growth and differentiation.
Implementation Method 1
The composition comprises naturally occurring chemotaxis, growth and stimulatory factors that recruit cells into the composition
Implementation Method 2
The composition can be formulated to be in liquid form at room temperature, typically 20° C. to 25° C., and in gel form at a temperature greater than room temperature or greater than 35° C.
Data Source
AI summary
Described herein are compositions comprising decellularized cardiac extracellular matrix and therapeutic uses thereof. Methods for treating, repairing or regenerating defective, diseased, damaged or ischemic cells, tissues or organs in a subject, preferably a human, using a decellularized cardiac extracellular matrix of the invention are provided. Methods of preparing cardiomyocyte culture surfaces and culturing cells with absorbed decellularized cardiac extracellular matrix are provided.