Decellularized Matrices As Cell-Instructive Scaffolds to Guide Tissue-Specific Regeneration

Abstract

Decellularized scaffolds are promising clinically translational biomaterials that can be applied to direct cell responses and promote tissue regeneration. Bioscaffolds derived from the extracellular matrix (ECM) of decellularized tissues can naturally mimic the complex extracellular microenvironment through the retention of compositional, biomechanical, and structural properties specific to the native ECM. Increasingly, studies have investigated the use of ECM-derived scaffolds as instructive substrates to recapitulate properties of the stem cell niche and guide cell proliferation, paracrine factor production, and differentiation in a tissuespecific manner. Here, we review the application of decellularized tissue scaffolds as instructive matrices for stem or progenitor cells, with a focus on the mechanisms through which ECMderived scaffolds can mediate cell behavior to promote tissue-specific regeneration. We conclude that although additional preclinical studies are required, ECM-derived scaffolds are a promising platform to guide cell behavior and may have widespread clinical applications in the field of regenerative medicine.

Culture on Tissue‐Specific Coatings Derived from α‐Amylase‐Digested Decellularized Adipose Tissue Enhances the Proliferation and Adipogenic Differentiation of Human Adipose‐Derived Stromal Cells

“…A secondary goal was to develop a deeper understanding of the potential benefits of applying adipose‐derived ECM as a tissue‐specific substrate for ASC expansion and adipogenic differentiation. Many studies assessing ECM‐derived biomaterials lack appropriate tissue‐type controls that are structurally and biomechanically similar, to be able to interpret whether there are tissue‐specific compositional effects on the cells . Hence, commercially sourced bovine tendon collagen served as a tissue‐type control based on our previous studies characterizing the protein composition of this specific source, as well as our previous success in applying α‐amylase‐digested COL to generate compositionally distinct porous foams relative to DAT…”

“…Many studies assessing ECM-derived biomaterials lack appropriate tissue-type controls that are structurally and biomechanically similar, to be able to interpret whether there are tissuespecific compositional effects on the cells. [41] Hence, commercially sourced bovine tendon collagen served as a tissue-type control based on our previous studies characterizing the protein composition of this specific source, [42] as well as our previous success in applying -amylase-digested COL to generate compositionally distinct porous foams relative to DAT. [32] As expected, digestion with -amylase better preserved the fibrillar structure of the ECM sources and retained a range of higher molecular weight proteins.…”

Tissue-Specific Decellularization Methods: Rationale and Strategies to Achieve Regenerative Compounds

“…The applications of decellularized materials and matrices in regenerative medicine context are multiple, including clinically used implantable materials, and continue to expand. For example, whole decellularized pieces are mainly used as scaffolds for transplantation purposes; dECM processed to form sheets and/or patches is useful in soft tissue and cardiac repair; Powder of demineralized bone matrix can be resuspended and be used to fill and heal bone defects; dECM-derived hydrogels are useful as injectable materials with regenerative properties; Hydrogels can be processed too, to generate inks and bioinks useful in 3D printing and electrospun-based strategies; dECM-derived scaffolds can be used as cell carriers for in vitro modeling or in vivo regenerative purposes [2,[13][14][15][16][17][18][19].…”

<p>Engineering of Aerogel-Based Biomaterials for Biomedical Applications</p>

“…[2][3][4] The use of native ECM is of special interest for cell culture and tissue engineering applications, due to the presence of intrinsic regulatory structure and bioactive factors. 5 Up to now, many efforts have been made to develop the ECM-like biomaterials through mimicking the biological structures and chemical properties of natural ECM.…”