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.

Statement of significance: More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel.

Keywords: Biomaterial; Decellularization; Extracellular matrix; Hydrogel; Injectable; Naturally derived; Regenerative medicine; Tissue engineering.

Figure 1

Overview of techniques used to characterize and to evaluate the cellular response to ECM hydrogels thus far. ECM hydrogels derived from various species, concentrations and processing methods are categorized only by source tissue.

Figure 2

General approaches to assess cellular response to ECM hydrogels. The response of various cell types in vitro or in vivo can be evaluated