The Current State of Extracellular Matrix Therapy for Ischemic Heart Disease

Figure 1. Components of ECM: Illustration summarizing the principal ECM components derived from myocardial ECM. Within the healthy myocardial ECM, components such as collagen, hyaluronan, and proteoglycans are present at varying levels. Following myocardial infarction (MI), components like fibrin, fibronectin, and periostin become prominent in the remodeling and repair processes. Additionally, during the early stages of fetal cardiac development, components such as agrin and nephronectin are observed in the ECM, playing key roles in the processes of proliferation and differentiation.

Figure 2. ECM in Ischemic Heart Disease (IHD): Schematic summarizing several primary ECMs with potential for treatment of IHD. The direct intracardiac administration of individual ECM components, such as collagen, glycoproteins, and proteoglycans, can facilitate the repair of myocardial tissue). Another approach involves the extraction and decellularization of the ECM from the tissues to leverage its entirety, encompassing all components and their intricate interactions with both each other and cellular elements in myocardium, thereby promoting optimal tissue repair. The bioengineering method involves generation of ECM through modifiable techniques which can be employed to achieve standardized and individualized treatments for IHD.

Figure 3. Application of ECM therapy and desired outcomes following therapy: Schematic highlighting two examples of applying ECM-based therapy. (Upper panel) Any form of ECM discussed can be loaded into an injection and applied directly into the infarcted myocardium. (Lower panel) ECM can be cut out into thin patches or loaded onto patches for delivery and applied directly over the infarcted surface of the heart. Following the application of ECM, several desirable outcomes including increased coronary angiogenesis leading to reduction in pathological remodeling, infarct size, and recovery of post-MI cardiac function are highlighted in the schematic.

Figure 4. Tissue-derived dECM: illustration depicting the fundamental decellularization process employed in obtaining tissue-derived ECM from various sources. The chosen tissue undergoes subdivision into small pieces, subsequently immersed in a detergent solution. This process serves to eliminate all cellular components while preserving the structural integrity and constituents inherent in the ECM.

Figure 5. Different Methods for Bioengineering of ECM: Diagram illustrating two examples of bioengineering techniques for the generation of 3D bioengineered ECM. In the first approach, molds of various shapes can be seeded with cells, leading to the formation of scaffold-less microtissues (upper panel). These microtissues generate ECM with a modifiable architecture, utilizing forces derived from the cells themselves. Alternatively, another method involves seeding cells into pre-existing scaffolds to generate ECM based on the physical properties of the scaffold (lower panel).