Decellularized extracellular matrix scaffolds: Recent trends and emerging strategies in tissue engineering

Abstract

The application of scaffolding materials is believed to hold enormous potential for tissue regeneration. Despite the widespread application and rapid advance of several tissue-engineered scaffolds such as natural and synthetic polymer-based scaffolds, they have limited repair capacity due to the difficulties in overcoming the immunogenicity, simulating in-vivo microenvironment, and performing mechanical or biochemical properties similar to native organs/tissues. Fortunately, the emergence of decellularized extracellular matrix (dECM) scaffolds provides an attractive way to overcome these hurdles, which mimic an optimal non-immune environment with native three-dimensional structures and various bioactive components. The consequent cell-seeded construct based on dECM scaffolds, especially stem cell-recellularized construct, is considered an ideal choice for regenerating functional organs/tissues. Herein, we review recent developments in dECM scaffolds and put forward perspectives accordingly, with particular focus on the concept and fabrication of decellularized scaffolds, as well as the application of decellularized scaffolds and their combinations with stem cells (recellularized scaffolds) in tissue engineering, including skin, bone, nerve, heart, along with lung, liver and kidney.

Bioinks Enriched with ECM Components Obtained by Supercritical Extraction

“…Most of the ECM-extraction protocols reported in the literature yield products that do not accurately depict the source ECM's composition and, importantly, functionality [12,13,39]. By comparing the amount of protein and sGAGs obtained using scCO 2 extraction with the standard protocols, it was clear that our methodologies lead to a significantly higher preservation of these components.…”

“…Overall, the approaches used so far to extract ECM rely on the treatment of tissue with harsh chemicals (mostly strong detergents) or extreme temperature to guarantee the successful removal of cellular contents [10,11]. Yet, many of the ECM components are significantly affected by those conditions, losing critical conformational arrangement or suffering degradation, which hinders the extract's overall level of complexity and biomimicry [12,13]. Therefore, milder extraction protocols to minimise this are still on the quest.…”

Matrix stiffness exacerbates the proinflammatory responses of vascular smooth muscle cell through the DDR1-DNMT1 mechanotransduction axis

“…Furthermore, mechanobiological study in vasculature may shed lights on the design and development of new tissue-engineered vascular scaffolds for achieving appropriate scaffolding mechanics and bioactivity. Indeed, prior attempts have been made to reach some of these objectives including the development of scaffolding materials with ideal mechanical properties and bioacitivities providing mechanical cues to guide cell behaviors during vascular regeneration [ 66 , 67 ]. Thus, we believe that the potential future applications of our study are numerous and promising.…”

Organ-Specific Endothelial Cell Differentiation and Impact of Microenvironmental Cues on Endothelial Heterogeneity

“…With regard to the brain, ECMs have been extracted and their compositions have been compared with the native tissue and Matrigel [180] or between different brain regions [181] using mass spectrometry; however, no endothelial studies have been performed with those yet. Recently, the use of organ-specific decellularized ECM hydrogels [182] and decellularized ECM scaffolds [183] have been reviewed elsewhere.…”