Decellularization in Tissue Engineering and Regenerative Medicine: Evaluation, Modification, and Application Methods

Abstract

Reproduction of different tissues using scaffolds and materials is a major element in regenerative medicine. The regeneration of whole organs with decellularized extracellular matrix (dECM) has remained a goal despite the use of these materials for different purposes. Recently, decellularization techniques have been widely used in producing scaffolds that are appropriate for regenerating damaged organs and may be able to overcome the shortage of donor organs. Decellularized ECM offers several advantages over synthetic compounds, including the preserved natural microenvironment features. Different decellularization methods have been developed, each of which is appropriate for removing cells from specific tissues under certain conditions. A variety of methods have been advanced for evaluating the decellularization process in terms of cell removal efficiency, tissue ultrastructure preservation, toxicity, biocompatibility, biodegradability, and mechanical resistance in order to enhance the efficacy of decellularization methods. Modification techniques improve the characteristics of decellularized scaffolds, making them available for the regeneration of damaged tissues. Moreover, modification of scaffolds makes them appropriate options for drug delivery, disease modeling, and improving stem cells growth and proliferation. However, considering different challenges in the way of decellularization methods and application of decellularized scaffolds, this field is constantly developing and progressively moving forward. This review has outlined recent decellularization and sterilization strategies, evaluation tests for efficient decellularization, materials processing, application, and challenges and future outlooks of decellularization in regenerative medicine and tissue engineering.

WITHDRAWN: Decellularized lung extracellular matrix scaffold promotes human embryonic stem cell differentiation towards alveolar progenitors

“…Pluripotent stem cell (PSC)-derived cells are potentially in uenced by ECM and exogenous signals such as paracrine-acting growth factors, and instructive memory in native ECM is able to developmentally determine cell fate and promote tissue-speci c differentiation [6]. In this regard, decellularized ECM has been generated from various organs, used as scaffold and recellularized with various cells to study cell-ECM interactions for organ engineering [6][7][8][9]. Therefore, decellularized lung scaffolds have been repopulated with primary cells or cells in predifferentiation states derived from PSCs to demonstrate the e cient generation of mature airway structures in-vitro [10,11].…”

Growth anisotropy of the extracellular matrix drives mechanics in a developing organ

“…This was achieved by exposing disc explants to the detergent Triton X-100 (referred to as ‘decellularization’ in the following, see methods) which results in the degradation of the lipid bilayer and a loss of cells and thus hydrostatic pressure on the surrounding ECM (Fig.5A+B). Chemical decellularization was used in various regenerative (Chen et al, 2016; Garcia-Puig et al, 2019; Sonpho et al, 2021) and biomedical approaches (Neishabouri et al, 2022) and decellularization by Triton X-100 retains ECM microstructure (Fernández-Pérez and Ahearne, 2019). The decellularization of 118hAEL discs results in a degradation and shrinking of the epithelial layers, well visible in cross-section views (Fig.5B top versus bottom ).…”

“…5A+B). Chemical decellularization was used in various regenerative (Chen et al, 2016;Garcia-Puig et al, 2019;Sonpho et al, 2021) and biomedical approaches (Neishabouri et al, 2022) and decellularization by Triton X-100 retains ECM microstructure (Fernández-Pérez and Ahearne, 2019). The decellularization of 118hAEL discs results in a degradation and shrinking of the epithelial layers, well visible in cross-section views (Fig.…”

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

“…This technique involves immersion of the organ in a decellularization solution, followed by shaking on a stir plate to facilitate the rupture, detachment, and removal of cellular components [ 112 ]. Protocols using this physical decellularization method have been described for numerous tissues, including cardiovascular tissue [ 18 , 113 , 114 ].…”