Joris van Dongen

310 Chapter 13 comprises the non-cellular component of the tissue, occupies the space between cells and functions as a scaffold to give structural support to cells. ECM is composed of extracellular macromolecules secreted by professional connective tissue cells such as fibroblasts. The two main classes of macromolecules in ECM are 1) strongly negatively charged polysaccharides such as glycosaminoglycans (GAGs) and proteoglycans (PGs) that embed the 2) proteinaceous fraction of ECMsuch as collagens. Collagen is themost abundant protein; and comprises about 30% of the tissue mass (percentage various within different tissues types) and there are 28 different types of collagens. PGs can either stimulate or inhibit angiogenesis in a context-dependent manner. By virtue of their charge, PGs and GAGs are very hydrophilic molecules that regulate tissue volume by water retention which makes ECM in fact a natural hydrogel. 17 Moreover, ECM serves as a slow release reservoir of growth factors that regulate behaviour of proximal cells. This ranges from suppression of apoptosis by joint action ECM molecules and growth factors to proliferation, differenation and migration. Growth factor binding the GAGs in the ECM depends on the presence of the so-called aminoterminal heparin- binding domain but also plain electrostatic or Van der Waals interactions may keep soluble factors bound to ECM. A manner to implement the extracellular matrix as a treatment or bioengineering tool is to produce ECM hydrogels. Various human or porcine tissues qualify to produce organ-specific ECM hydrogels including heart 18,19 , lung 20 , pancreas 21 , skin 22 , and adipose tissue. 23 We surmise that these ECM hydrogels may act to retains growth factors with the benefit that these are released with distinct kinetics over time. The released growth factors are able to induce angiogenesis by stimulation of endothelial cells to form new blood vessels which in turn stimulates tissue regeneration resulting in wound healing. 24 Wound healing is especially impaired in diabetic patients because of decreased peripheral blood flow leading to diabetic ulcers formation. Diabetes affects ASCs and SVF, therefore, clinical use of an ECM-derived hydrogel from healthy donors is more suitable for patients suffering from diabetes mellitus. ECM hydrogels may also be applicable for 3D culturing, 3D bioprinting and in vivo tissue regeneration. 25 These can be in a donor-independent fashion and over a species barrier while SVF which can be used only as an allogeneic transplant otherwise immunological rejection would occur. More preliminary studies are needed before ECM hydrogel can enter clinical trials. The decellularization of adipose tissue precedes the generation of ECM hydrogels, the latter is done by mild digestion under low pH with pepsin. In particular, decellularization involves multiple steps with harsh chemicals such as detergents that are incompatible with survival of cells. Therefore,