In Vivo Response of Acellular Porcine Pericardial for Tissue Engineered Transcatheter Aortic Valves

Abstract

Current heart valve prostheses have limitations that include durability, inability to grow in pediatric patients, and lifelong anticoagulation. Transcatheter aortic valve replacements are minimally invasive procedures, and therefore have emerged as an alternative to traditional valve prostheses. In this experiment, the regenerative capacity of potential tissue engineered transcatheter valve scaffolds (1) acellular porcine pericardium and (2) mesenchymal stem cell-seeded acellular porcine pericardium were compared to native porcine aortic valve cusps in a rat subcutaneous model for up to 8 weeks. Immunohistochemistry, extracellular matrix evaluation, and tissue biomechanics were evaluated on the explanted tissue. Acellular valve scaffolds expressed CD163, CD31, alpha smooth muscle actin, and vimentin at each time point indicating host cell recellularization; however, MSC-seeded tissue showed greater recellularization. Inflammatory cells were observed with CD3 biomarker in native porcine pericardial tissue throughout the study. No inflammation was observed in either acellular or MSC-seeded scaffolds. There was no mechanical advantage observed in MSC-seeded tissue; however after the first week post-explant, there was a decrease in mechanical properties in all groups (p < 0.05). MSC-seeded and acellular porcine pericardium expressed decreased inflammatory response and better host-cell recellularization compared to the native porcine aortic valve cusps.

Acellular pericardium: A naturally hierarchical, osteoconductive, and osteoinductive biomaterial for guided bone regeneration

“…The presence of macrophages and multinuclear giant cells contribute to the biodegradation of biomaterials and to tissue regeneration. Reza et al implanted APP subcutaneously in a mouse dorsum model and found angiogenesis and M2 macrophages recruitment that were closely related to tissue regeneration (Reza Khorramirouz, Noble, Morse, Lerman, & Young, 2019). Rothemal et al applied APP as the barrier membrane in canine ridge preservation, and found that APP facilitated early vascularization and integration with the surrounding tissues (Daniel Rothamel et al, 2012).…”

Development of Tissue Engineered Heart Valves for Percutaneous Transcatheter Delivery in a Fetal Ovine Model

“…In another study, transcatheter TEHVs, derived from porcine pericardium, were implanted in the subcutaneous tissue of rats and demonstrated limited inflammation and a loss of mechanical properties over the first few weeks post-implantation. These valves, however, were not tested in a functional biological position ( 42 ). Development of the large animal model presented in this work will allow for a deeper understanding of these biological mechanisms, as well as the critical design parameters needed to design an ideal TEHV, such as degradation profile and inflammatory status ( 40 ).…”

Pilot study on cardiogenic differentiation capability of rabbit mesenchymal stem cells

“…Up to date, a little is known about the multipotent properties of pericardial MSCs. Most of the reported studies are focused on the hydrogel embedded implantation of a new form of adult cardiac stem cells, as called cardiospheres (CSPs), into the pericardial cavity (16,34) or using the de-cellularized pericardium membrane as a scaffold for MSCs culturing (10,14). The CSPs is a new approach of stem cell therapy for myocardial infarction treatment, using the ability of those cells to differentiate into cardiomyocytes in vivo (34).…”