Full‐Thickness Heart Repair with an Engineered Multilayered Myocardial Patch in Rat Model

Abstract

Structural cardiac defects, such as Tetralogy of Fallot, often requires surgical placement of a patch to expand the right ventricular outflow tract (RVOT) in an area normally consisting of contractile myocardial tissue. Current cardiac patch materials are biologically inert and will not grow with a pediatric patient, often requiring reoperations. In this study, novel multi-layered scaffolds with a polycaprolactone core, a chitosan-based scaffold, and either gelatin or decellularized porcine heart matrix were implanted into a full thickness rat right ventricle defect for up to 8 weeks. The results show that engineered scaffolds were biodegradable and promoted tissue remodeling. Histological analysis of control fixed pericardium patches showed little to no cellular infiltration, while engineered scaffolds had significant muscular and vascular cell remodeling. Quantitative MRI revealed that left ventricular ejection fractions were stabilized in all patched hearts after 8 weeks, and the right ventricular ejection fraction in hearts with engineered patches was significantly greater than hearts with control pericardium patches. In addition, patches with heart matrix promoted a denser vascular network and a higher M2/M1 inflammatory macrophage ratio when compared to patches containing only gelatin. Collectively, these results show that these multi-layered patches are capable of full thickness defect repair and regeneration.

Decellularized Extracellular Matrix Materials for Cardiac Repair and Regeneration

“…The patch had ideal potential for direct use as a thick patch for myocardial replacement. Pok et al modified the patch by adding a polycaprolactone (PCL) core, and tested the therapeutic potential of the patch in a rat infarction model . Pourfarhangi et al evaluated the optimized ratio of cECM and chitosan for improving CPC function, and determined that higher cECM composition in composite patches improved CPC viability .…”

“…In surgical treatments for Tetralogy of Fallot, patches most often composed of nondegradable, bioinert materials such as nylon or noncardiac specific materials such as SIS are placed across the right ventricular outflow tract (RVOT). Pok et al generated a bioactive, degradable full‐thickness cardiac patch composed cECM/chitosan and PCL layers for use as a RVOT patch and compared the system to patches composed of gelatin/chitosan/PCL and pure bovine pericardium . By week 8, both gelatin and cECM patches showed similar decreases in PCL thickness.…”

Biomimetic Artificial Basilar Membranes for Next‐Generation Cochlear Implants

“…In addition, the ABMs should be able to sense a wider frequency range of 100 Hz to 8 kHz, and be sensitive enough to detect sound with a minimum of ≈40 dB SPL . Packaging for chemical and electrical stability and subsequent verification of long‐term biocompatibility are also essential . In addition to optimizing the ABM itself, research on the whole CI system should be performed for the development of next‐generation devices.…”

Human cardiac extracellular matrix‑chitosan‑gelatin composite scaffold and its endothelialization

“…Previous studies found that ECM can be harvested from tissues such as cartilage, skeletal muscle, tendons, adipose tissue, vessels, lung, liver, intestine (17,21,22) and bovine ureter (23), and may be applied as biological scaffolds with beneficial results. Previous studies in which porcine heart matrix was used for construction of tissue engineered heart patches demonstrated that porcine ECM could support cardiomyocytes, improved heart function and was capable of heart defect repair (24,25). However, ECM is frequently derived from non-cardiac or heart tissue of other species.…”