Extracellular matrix - derived hydrogels for Tissue Engineering

Tissue engineering (TE) is an interdisciplinary field that creates biological alternatives to restore or enhance the function of damaged tissues or organs. One critical aspect in creating such alternatives for perfused tissues is their vascularization since cell necrosis is a common outcome if the diffusion of oxygen and nutrients is not assured. Incorporating angiogenic chemical cues in these models may be a potential solution for this problematic. In this line, adipose tissue-derived stromal vascular fraction (SVF) is a heterogeneous cell fraction that was shown to undergo spontaneous vasculogenesis in vitro due to enabling growth factor secretion and extracellular matrix (ECM) composition. The ECM is an organized network composed of several macromolecules and comprises the non-cellular component of living tissues. This network functions as a 3D matrix with a unique chemical composition that supports cellular activities and responses required for tissue homeostasis. When developing TE constructs, it is crucial to mimic as much as possible native ECM in order to better approximate the cellular environment to the native tissue dynamics. Hydrogels are well-established tools that can be used as ECM surrogates to provide mechanical support and biological cues and direct cell behavior. Therefore, the aim of this work was to achieve an angiogenic/vasculogenic hydrogel derived from SVF-derived ECM. We were able to isolate ECM from cell sheets made of SVF-derived adipose stem cells (ASCs) and develop an ECM-like hydrogel. ASCs cell sheets were decellularized by a combination of freeze-thaw cycles and a nuclease treatment. The samples were freeze-dried and digested with an acidic pepsin solution, and a hydrogel was formed after pH neutralization and temperature increase. Through circular dichroism (CD), we were able to detect the triple helix structure of proteins, confirming protein structural stability after the extraction protocol. Additional studies are ongoing to better characterize the obtained hydrogel and assess its angiogenic/vasculogenic potential. If successful, this strategy of obtaining angiogenic/vasculogenic ECM-like hydrogels has the potential to be used in a broad range of different applications in TE and biomedical research.