Extracellular matrix hydrogels from decellularized tissues: Structure and function

Abstract

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed.

Kidney decellularized extracellular matrix hydrogels: Rheological characterization and human glomerular endothelial cell response to encapsulation

“…Once the digest is neutralized, thus inactivating the enzyme, and brought to physiological temperature and salt concentration, the collagen and other matrix peptides self-assemble in an entropy-driven process 51,52 . The resulting kidney dECM hydrogels possess a loosely organized fibrous organization with an interconnected pore structure as visualized under SEM (Figure 3A-D) that is comparable to collagen I hydrogels and various dECM hydrogels characterized by other groups 30 .…”

“…Biochemical characterization of decellularized kidney tissues presented in this work was performed, demonstrating retention of key ECM proteins such as collagen I, collagen IV, laminin, and sulfated GAGs. However, decellularized ECM hydrogels are complex and may contain any combination of proteins, cryptic peptides and bioactive motifs, sequestered growth factors, cytokines, chemokines, and even matrix-bound nanovesicles 30 . Any of these additional bioactive components may present negative or undesired signaling cues to specific cell types.…”

“Tissue Papers” from Organ‐Specific Decellularized Extracellular Matrices

“…[3,39] These additional solubilization steps are not only time consuming and tissue/organ specific, but are biased toward retaining certain dECM components over others, resulting in the final dECM biomaterials being further removed in both composition and structure from the native tissue/organ extracellular matrices from which they are derived. [40] The process we present here is entirely physical in nature, does not require acid, basic, or enzymatic digestion of the dECM prior to use, and thus is primarily independent of tissue and organ type, composition, and source, while simultaneously retaining much of the composition and structure of the native dECM.…”

Scarring vs. functional healing: Matrix-based strategies to regulate tissue repair

“…Hydrogels have been formed and characterized from a range of decellularized tissues including adipose, gastrointestinal, heart, lung, and skin among others. A recent review nicely summarizes the structural and functional characteristics of such gels [162]. Tissue derived hydrogels have mechanical properties that are tunable by varying the concentration of matrix, providing some application-specific control of material properties.…”