In Vivo Assessment of Decellularized Porcine Myocardial Slice as an Acellular Cardiac Patch

Abstract

Acellular cardiac patches made of various biomaterials have shown to improve heart function after myocardial infarction (MI). Extracellular matrix scaffold derived from a decellularized tissue has unique advantages to serve as an acellular cardiac patch due to its biomimetic nature. In this study, we examined the therapeutic outcomes of using a decellularized porcine myocardium slice (dPMS) as an acellular patch in a rat acute MI model. dPMSs with two different thicknesses (300 and 600 μm) were patched to the infarcted area of the rat myocardium, and their effects on cardiac function and host interactions were assessed. We found that the implanted dPMS firmly attached to host myocardium after implantation and prevented thinning of the left ventricular (LV) wall after an MI. A large number of host cells were identified to infiltrate into the implanted dPMS, and a significant number of vessel structures was observed in the dPMS and infarcted area. We detected a significantly higher density of M2 macrophages in the groups treated with dPMSs as compared to the MI group. Contraction of the LV wall and cardiac functional parameters (left ventricular ejection fraction and fractional shortening) was significantly improved in the treatment groups (300 and 600 μm dPMS) 4 weeks after surgery. Our results proved the therapeutic benefits of using dPMS as an acellular cardiac patch for the treatment of acute myocardial infarction.

Engineering Human Cardiac Muscle Patch Constructs for Prevention of Post-infarction LV Remodeling

“…Paracrine signaling was further evidenced by a study where exosomes secreted from combination of iPSC-derived CMs, ECs, and SMCs yielded cardioprotective effects similar to that obtained from direct cells injection in a porcine model of MI (195). Further, acellular hCMPs composed of non-viable/irradiated cells (39) or decellularized porcine myocardial tissues (139) have shown therapeutic benefits after transplantation, through the proposed mechanism of mechanical stabilization. Thus, the therapeutic benefits associated with hCMP transplantation could be a combination of any or all of mechanisms including remuscularization, paracrine signaling, and mechanical stabilization (202,207).…”

Biomaterials-based Approaches for Cardiac Regeneration

“…Specifically, materials of natural sources can better recapitulate the extracellular matrix (ECM) microenvironment and facilitate in vivo biochemical signaling. Natural materials used in cardiac patches commonly include decellularized ECM, 25) 26) 27) polysaccharides such as chitosan (CS), 28) 29) 30) and peptides such as collagen, 20) 21) 22) 23) 24) 25) 26) 27) 28) 29) 30) 31) 32) 33) 34) gelatin, 35) 36) 37) fibrin, 38) 39) and silk fibroin (SF). 28) 40) …”

“…Patches without any biomolecules are also able to support cardiac function through mechanical support of the scaffold that facilitates cell migration, angiogenesis, 34) increased cell infiltration, and macrophage accumulation. 27) …”

Therapeutic Acellular Scaffolds for Limiting Left Ventricular Remodelling-Current Status and Future Directions

“…At 4 weeks, in comparison to 300 μm thickness dPMS, 600 μm patch was more effective in preventing thinning of LV wall and fractional shortening (FS). In addition to this, the 300 µm thickness patch degraded significantly as observed after 4 weeks of transplantation thus highlighting that the durability of dPMS can be compromised in long-term applications [ 21 ]. Unlike other patches, the capability of dPMS to attach to host tissues might represent a unique advantage.…”