Abstract
When a tissue or an organ is considered, the attention inevitably falls on the complex and delicate mechanisms regulating the correct interaction of billions of cells that populate it. However, the most critical component for the functionality of specific tissue or organ is not the cell, but the cell-secreted three-dimensional structure known as the extracellular matrix (ECM). Without the presence of an adequate ECM, there would be no optimal support and stimuli for the cellular component to replicate, communicate and interact properly, thus compromising cell dynamics and behaviour and contributing to the loss of tissue-specific cellular phenotype and functions. The limitations of the current bioprosthetic implantable medical devices have led researchers to explore tissue engineering constructs, predominantly using animal tissues as a potentially unlimited source of materials. The high homology of the protein sequences that compose the mammalian ECM, can be exploited to convert a soft animal tissue into a human autologous functional and long-lasting prosthesis ensuring the viability of the cells and maintaining the proper biomechanical function. Decellularization has been shown to be a highly promising technique to generate tissue-specific ECM-derived products for multiple applications, although it might comprise very complex processes that involve the simultaneous use of chemical, biochemical, physical and enzymatic protocols. Several different approaches have been reported in the literature for the treatment of bone, cartilage, adipose, dermal, neural and cardiovascular tissues, as well as skeletal muscle, tendons and gastrointestinal tract matrices. However, most of these reports refer to experimental data. This paper reviews the most common and latest decellularization approaches that have been adopted in cardiovascular tissue engineering. The efficacy of cells removal was specifically reviewed and discussed, together with the parameters that could be used as quality control markers for the evaluation of the effectiveness of decellularization and tissue biocompatibility. The purpose was to provide a panel of parameters that can be shared and taken into consideration by the scientific community to achieve more efficient, comparable, and reliable experimental research results and a faster technology transfer to the market.
Highlights
In biological tissue, the main component in terms of volume is not related to the cells, but rather to the cell-secreted three-dimensional extracellular matrix (ECM; Table 1)
A number of different animal-tissue-derived ECMs have been used to produce bioprosthetic substitutes for various applications such as for bone, cartilage, muscle, tendon, vascular graft, heart valve, nerve, dermal and gastrointestinal tract tissue repair or replacement (Badylak et al, 2009; Brown and Badylack, 2014; Folli et al, 2018). Many of these biological medical devices have been subjected to treatments that allow preservation of their functionality, but not the viability of their cellular content
Non-viable tissue is not capable of ECM regeneration and remodelling, limiting their lifespan and imposing the need for frequent replacement, forcing patients to multiple surgical interventions. To overcome this limitation and develop viable and functional engineered animal-derived ECMs, native tissues have been subjected to controlled removal of their cellular content, generating a decellularized three-dimensional scaffold (Crapo et al, 2011)
Summary
Representing the structural proteins that are the most abundant in the ECM. The molecular feature of collagen is the glycine–X–Y triplet repeat, where X frequently represents proline and Y represents hydroxyproline. Type III Fibrillar collagen, primarily found in the ECM of elastic tissues such as lung and blood vessels. Elastin endows the ECM with elastic recoil and is abundant in tissues that require frequent expansion and contraction. GAGs are unbranched carbohydrates that consist of repeating disaccharide subunits that vary in number, these saccharide elements can undergo modification by epimerization and sulfation resulting in a vast diversity of GAG chains. Heparan sulfate Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues It occurs as a proteoglycan (PG) in which two or three HS chains are attached near to the cell surface or ECM proteins. They are present in the cornea, cartilage, bones, and horns of animals
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