Decellularized extracellular matrix scaffolds: Recent trends and emerging strategies in tissue engineering

Decellularized matrices in regenerative medicine.

Twenty years after the initial description of a tissue engineered construct, 3-dimensional human cardiac tissues of different kinds are now generated routinely in many laboratories. Advances in stem cell biology and engineering allow for the generation of constructs that come close to recapitulating the complex structure of heart muscle and might, therefore, be amenable to industrial (eg, drug screening) and clinical (eg, cardiac repair) applications. Whether the more physiological structure of 3-dimensional constructs provides a relevant advantage over standard 2-dimensional cell culture has yet to be shown in head-to-head-comparisons. The present article gives an overview on current strategies of cardiac tissue engineering with a focus on different hydrogel methods and discusses perspectives and challenges for necessary steps toward the real-life application of cardiac tissue engineering for disease modeling, drug development, and cardiac repair.

Engineering Cardiac Muscle Tissue: A Maturating Field of Research.

Decellularized extracellular matrix (dECM) is a promising biomaterial for repairing cardiovascular tissue, as dECM most effectively captures the complex array of proteins, glycosaminoglycans, proteoglycans, and many other matrix components that are found in native tissue, providing ideal cues for regeneration and repair of damaged myocardium. dECM can be used in a variety of forms, such as solid scaffolds that maintain native matrix structure, or as soluble materials that can form injectable hydrogels for tissue repair. dECM has found recent success in many regeneration and repair therapies, such as for musculoskeletal, neural, and liver tissues. This review focuses on dECM in the context of cardiovascular applications, with variations in tissue and species sourcing, and specifically discusses advances in solid and soluble dECM development, in vitro studies, in vivo implementation, and clinical translation.

Decellularized Extracellular Matrix Materials for Cardiac Repair and Regeneration

Inverted orientation improves decellularization of whole porcine hearts

The ultimate solution for patients with end-stage heart failure is organ transplant. But donor hearts are limited, immunosuppression is required, and ultimately rejection can occur. Creating a functional, autologous bio-artificial heart could solve these challenges. Biofabrication of a heart comprised of scaffold and cells is one option. A natural scaffold with tissue-specific composition as well as micro- and macro-architecture can be obtained by decellularizing hearts from humans or large animals such as pigs. Decellularization involves washing out cellular debris while preserving 3D extracellular matrix and vasculature and allowing "cellularization" at a later timepoint. Capitalizing on our novel finding that perfusion decellularization of complex organs is possible, we developed a more "physiological" method to decellularize non-transplantable human hearts by placing them inside a pressurized pouch, in an inverted orientation, under controlled pressure. The purpose of using a pressurized pouch is to create pressure gradients across the aortic valve to keep it closed and improve myocardial perfusion. Simultaneous assessment of flow dynamics and cellular debris removal during decellularization allowed us to monitor both fluid inflow and debris outflow, thereby generating a scaffold that can be used either for simple cardiac repair (e.g. as a patch or valve scaffold) or as a whole-organ scaffold.

Decellularization of Whole Human Heart Inside a Pressurized Pouch in an Inverted Orientation

In practice, atrial fibrillation (AF) is typically managed by controlling ventricular rate given similar long-term outcomes and a more tolerable drug profile when compared to rhythm control. However, despite treatment via rate control, patients remain at increased risk for cardiovascular complications. This systematic review provides a summary of literature evaluating the effectiveness of early rhythm control (ERC, initiated within 2 years of diagnosis) in AF in reducing cardiovascular complications. A systematic review utilizing the MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews was performed to identify literature evaluating effectiveness of rhythm control strategies and cardiovascular complication reduction rates in ERC. A total of three literature articles meeting the inclusion and exclusion criteria were included for evaluating the benefit of ERC. One of these examined was a trial that directly compared antiarrhythmic drug (AAD) versus catheter ablation (CA) therapy in maintenance of sinus rhythm (SR). This systematic review shows that ERC is associated with a reduction of cardiovascular events in AF patients compared to other treatment strategies.

https://cardiologyres.org/index.php/Cardiologyres/article/download/1399/1335

Cardiovascular Outcomes With an Early Rhythm Control Strategy in Atrial Fibrillation: A Systematic Review

Recurrent right ventricular pseudoaneurysm following recent repair in a patient with tof

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Papers

Inverted orientation improves decellularization of whole porcine hearts

Decellularization of Whole Human Heart Inside a Pressurized Pouch in an Inverted Orientation

Cardiovascular Outcomes With an Early Rhythm Control Strategy in Atrial Fibrillation: A Systematic Review

Recurrent right ventricular pseudoaneurysm following recent repair in a patient with tof