Executive Summary : | Exo-MECHANOLOGY is a project aimed at improving the yield of Extracellular Vehicles (EVs) from milliliters to a liter, facilitating their translation from laboratory projects to clinical precision therapeutics. EVs are tiny membranous vesicles released by almost all cell types and play a significant role in cell-to-cell communication, epigenetic regulation, and transportation of proteins and genetic materials. They act as clinically valuable tools for diagnosis, prognosis, and targeted treatment when engineered to deliver therapeutic cocktails. The proposal aims to manipulate the ECM mechanobiology of human adipose stem cells (hASCs) using Indian nonmulberry silk protein-based biomaterials to gain insight into how ECM mechanical stiffness governs the yield and composition of hASCs-derived EVs. By measuring Young's modulus and 3D surface stress of silk biomaterials, the interstitial force experienced by hASCs will be quantified, which will be related to the secretion of EVs by means of yield, composition, and duration of secretion. The study will also evaluate the proliferation and metastasis of osteosarcoma cells after treating with EVs as a proof-of-concept. Combining material science, cell biology, and biophysical techniques will reveal the currently unknown mechano-transduction mechanism of EV formation, leading to novel strategies in precision medicine by employing patients' own ASC-derived engineered EVs. |