Decellularization Strategies for Regenerating Cardiac and Skeletal Muscle Tissues

Abstract

Cardiovascular disease is the leading cause of death worldwide and is associated with approximately 17.9 million deaths each year. Musculoskeletal conditions affect more than 1.71 billion people globally and are the leading cause of disability. These two areas represent a massive global health burden that is perpetuated by a lack of functionally restorative treatment options. The fields of regenerative medicine and tissue engineering offer great promise for the development of therapies to repair damaged or diseased tissues. Decellularized tissues and extracellular matrices are cornerstones of regenerative biomaterials and have been used clinically for decades and many have received FDA approval. In this review, we first discuss and compare methods used to produce decellularized tissues and ECMs from cardiac and skeletal muscle. We take a focused look at how different biophysical properties such as spatial topography, extracellular matrix composition, and mechanical characteristics influence cell behavior and function in the context of regenerative medicine. Lastly, we describe emerging research and forecast the future high impact applications of decellularized cardiac and skeletal muscle that will drive novel and effective regenerative therapies.

Application of Acellular Dermal Matrix in Gynaecology—A Current Review

“…The immune response is mainly directed against the proteins and lipids of cell membranes; thus, cell extraction from tissue is a promising method to avoid the creation of a post-transplant immune response in the body of the recipient [ 4 , 12 , 13 , 14 , 15 , 16 ]. The removal of cellular components should minimize the immunologically induced inflammatory process, which may weaken the biodegradation process of the transplanted bioprosthesis [ 15 ].…”

“…The procedure of removing cells from allogeneic human dermis results in a cell-free, non-immunogenic matrix composed of extracellular matrix (ECM) elements that can be re-inhabited by autologous cells. Such cell-free dermal matrices (ADMs) can also stimulate natural regenerative and reconstructive mechanisms [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

“…Based on the results of numerous studies, it has also been shown that cell-free ECM scaffolds are able to propagate and support the growth and differentiation of many types of cells in vitro and induce constructive tissue remodelling processes after in vivo transplantation [ 7 , 8 , 9 , 10 , 11 ]. Thus, the use of three-dimensional ECM scaffolds obtained from tissues or whole organs that have undergone cell removal procedures is an increasingly used strategy of regenerative medicine and tissue engineering [ 4 , 5 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

The extracellular matrix differentially directs myoblast motility in distinct forms of muscular dystrophy

“…Generation of acellular myoscaffolds using chemical decellularization. For more than a decade, decellularized scaffolds have been generated from heart and muscle and studied for their ability to support cellular regeneration (reviewed in (Tan et al, 2022)). Recently Stearns-Reider et al published an "on-slide" decellularization method using 30µm tissue sections exposed to 1% SDS for 40 mins to generate dECM myoscaffolds (Stearns-Reider et al, 2022).…”

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

“…This enzyme is used in many decellularization protocols targeting the C-side bonds in lysine and arginine amino acids but disrupting the tissue microstructure when applied for too long. Trypsin is mainly used with detergents or enzymatic chelating agents (e.g., ethylenediaminetetraacetic acid—EDTA) [ 93 , 95 , 96 ]. A study published in 2013 by Merna et al demonstrated that decellularization of whole porcine hearts using trypsin significantly decreased DNA while severely reducing the structure and mechanical integrity of the ECM [ 79 ].…”