Cryomedical technologies as a key to effective decellularization in the creation of scaffolds for vascular transplantation

Abstract

Background. Cardiovascular diseases (CVDs) rank among the top three causes of death worldwide. In Europe, 3.9 million deaths annually are attributed to CVDs, with 1.8 million occurring among citizens of European Union (EU) countries. The total cost of treating patients with CVDs in EU countries amounts to €210 billion per year. Currently, the primary treatment strategy for patients with advanced stages of CVD remains bypass surgery. A significant increase in demand for vascular grafts over the past decade, particularly small-caliber vessels for cardiovascular bypass procedures, combined with a shortage of donor vessels and the limitations of artificial prostheses, makes the tissue engineering of vascular grafts a high-demand field. Purpose – to characterize modern approaches to creating decellularized vascular scaffolds based on data from open sources. Materials and Methods. The selection of publications was conducted using databases such as PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection, and others, focusing on contemporary methods for creating decellularized scaffolds. The first stage involved searching for literature sources using Keywords: decellularization, extracellular matrix, scaffold. In the second stage, article abstracts were reviewed, and publications not meeting the study criteria were excluded. The third stage involved examining the full texts of selected articles for compliance with inclusion criteria and research relevance. Inclusion criteria for publications subjected to content analysis included: 1) coverage of current information on the creation of decellularized scaffolds; 2) alignment of studies with key principles of evidence-based medicine; 3) open access to the full-text article. Results. The first attempt to create a blood vessel substitute using tissue engineering methods was made by Weinberg C.B. & Bell E. in 1986. Biological scaffolds, composed of extracellular matrix (ECM), are commonly used for various reconstructive surgical procedures and are increasingly employed in regenerative medicine strategies for tissue and organ replacement. ECM is a complex network of macromolecules that provides an appropriate local microenvironment for cell survival and activity in vivo, influencing cell shape, metabolism, function, migration, proliferation, and differentiation. A scaffold, in turn, can be defined as a three-dimensional platform necessary for actions ranging from cell-biomaterial interaction and cell adhesion to controlled biodegradation rates that correspond to tissue regeneration. Decellularization is a method for removing cellular components from organs or tissues to create an acellular scaffold composed of tissue ECM capable of providing a biomimetic microenvironment. The physicochemical signals and biological efficacy of ECM scaffolds can be maintained after decellularization, thus providing a substrate for mechanical support and a biological 3D carrier for subsequent recellularization. The complexity and duration of decellularization protocols are generally proportional to the degree of geometric and biological preservation desired for the tissue after processing. Conclusions. The rising incidence of CVDs and the need for surgical intervention have underscored the necessity, among other things, of creating artificial small-caliber vascular grafts – substitutes for blood vessels, especially those under 6 mm in diameter. Various sources, including human and animal cadavers, have been identified as sources of native vessels for decellularization. The creation of a cellular pattern is a new trend that is actively pursued, directly offering spatial control over angiogenesis, closely mimicking the natural environment. Cryopreservation is one of the most common procedures for graft storage. The freezing-thawing process effectively lyses cells in tissues and organs and is one of the most promising approaches to decellularization in the development of vascular scaffolds.

Keywords

• decellularization vascular scaffold freezing-thawing extracellular matrix tissue-engineered vascular graft mesenchymal stem cells cytolysis