Decellularized Extracellular Matrix Scaffolds for Cardiovascular Tissue Engineering: Current Techniques and Challenges

Abstract

Cardiovascular diseases are the leading cause of global mortality. Over the past two decades, researchers have tried to provide novel solutions for end-stage heart failure to address cardiac transplantation hurdles such as donor organ shortage, chronic rejection, and life-long immunosuppression. Cardiac decellularized extracellular matrix (dECM) has been widely explored as a promising approach in tissue-regenerative medicine because of its remarkable similarity to the original tissue. Optimized decellularization protocols combining physical, chemical, and enzymatic agents have been developed to obtain the perfect balance between cell removal, ECM composition, and function maintenance. However, proper assessment of decellularized tissue composition is still needed before clinical translation. Recellularizing the acellular scaffold with organ-specific cells and evaluating the extent of cardiomyocyte repopulation is also challenging. This review aims to discuss the existing literature on decellularized cardiac scaffolds, especially on the advantages and methods of preparation, pointing out areas for improvement. Finally, an overview of the state of research regarding the application of cardiac dECM and future challenges in bioengineering a human heart suitable for transplantation is provided.

From waste to wealth: Repurposing slaughterhouse waste for xenotransplantation

“…In preclinical and clinical investigations, ECM scaffolds are frequently used for reconstructive and regenerative applications (Brown and Badylak, 2014;Aamodt and Grainger, 2016;Nowocin et al, 2016;Xu et al, 2017;Jiang et al, 2021;Anderson et al, 2022;Barbon et al, 2022;Barbulescu et al, 2022;Wang et al, 2022b;Yesantharao and Nguyen, 2022;Zhang et al, 2022;Shakeel and Corridon, 2023a). Naturally occurring ECM-based biopolymers derived from harvested human (Kumar Kuna et al, 2018) and animal (Kumar Kuna et al, 2018) organs and tissues, as well as agarose (Salati et al, 2020), alginate (Ahmad Raus et al, 2021), chitosan (Sultankulov et al, 2019), and cellulose (Silva et al, 2022), can stimulate angiogenesis, growth, and differentiation of repopulating cells.…”

Decellularized periosteum promotes guided bone regeneration via manipulation of macrophage polarization

“…The goal of tissue decellularization is to remove as much immunogenic cellular components as possible while preserving the original ultrastructure and composition of the tissue ECM [14,16,24]. A variety of techniques can be used to decellularize tissue, including physical agents, chemical agents, and enzymes.…”

“…It has been shown that the decellularization process efficiently removes antigenic cellular components while retaining the natural 3D ultrastructure complete with the native ECM composition. Studies have demonstrated the feasibility of preparing decellularized tissue ECM scaffolds and applied them in the repair of multiple types of tissues and organs with varying degrees of success [14][15][16]. Although tissue-derived ECM scaffolds are generally used for the repair of non-homologous anatomic sites, site-specific homologous tissue scaffolds have been shown to be more effective than nonsite-specific tissue scaffolds in remodeling constructive tissue.…”

Biomedical Application of Decellularized Scaffolds

“…Common reagents are acetic acid, peracetic acid, hydrochloric acid, sulfuric acid, and ammonium hydroxide. They effectively destroy cell membranes and internal organelles. − Poornejad et al studied the effects of five decellularized agents (sodium hydroxide, peracetic acid, Triton X-100, sodium lauryl sulfate, and trypsin) on kidney tissue of pigs. The results showed that sodium hydroxide was the most effective cell scavenger, and although it caused the most significant damage to glycosaminoglycan, the cells treated with it had the highest activity and proliferation capacity after recellularizating.…”

“…But the availability of suitable artificial blood vessels is limited. Recently, decellularized blood vessels have been found to have good vascular properties. − …”