Extracellular vesicle-matrix interactions

Extracellular vesicles (EVs) are lipid-bound nanoscale mediators of intercellular communication. This Review discusses EVs in the context of the extracellular matrix, highlighting how the understanding of their interactions inspires materials design to control the release, retention and production of EVs for various biological and therapeutic applications. The extracellular matrix (ECM) harbours various signals to control cellular functions and the materiality of tissues. Most efforts to synthetically reconstitute the matrix by biomaterial design have focused on decoupling cell-secreted and polymer-based cues. Cells package molecules into nanoscale lipid-membrane-bound extracellular vesicles (EVs) and secrete them. Thus, EVs inherently interact with the meshwork of the ECM. In this Review, we discuss various aspects of EV-matrix interactions. Cells receive feedback from the ECM and leverage intracellular processes to control the biogenesis of EVs. Once secreted, various biomolecular and biophysical factors determine whether EVs are locally incorporated into the matrix or transported out of the matrix to be taken up by other cells or deposited into tissues at a distal location. These insights can be utilized to develop engineered biomaterials in which EV release, retention and production can be precisely controlled to elicit various biological and therapeutic outcomes.