No abstract

8Epithelial organoids are now an important tool in fields ranging from regenerative medicine to 9 drug discovery. Organoid culture requires Matrigel, a complex, tumor-derived, extracellular 10 matrix. An alternative completely synthetic matrix could improve culture reproducibility, clarify 11 mechanistic phenomena, and enable applications involving human implantation. Here, we 12 designed synthetic matrices with tunable biomolecular and biophysical properties that allowed us 13 to identify critical gel parameters in organoid formation. Inspired by known epithelial integrin 14 expression in the proliferative niche of the human intestine, we identified an a2b1 integrin-binding 15 peptide as a critical component of the synthetic matrix that supports human duodenal colon and 16 endometrial organoid propagation. We show that organoids emerge from single cells, retain their 17 proliferative capacity, are functionally responsive to basolateral stimulation and have correct 18 apicobasal polarity upon induction of differentiation. The local biophysical presentation of the 19 cues, rather than bulk mechanical properties, appears to be the dominant parameter governing 20 epithelial cell proliferation and organoid formation in the synthetic matrix. 21 . 22

Nanoemulsions containing hydrophobic drugs have a great potential in the pharmaceutical industries to improve the bioavailability of the drug. However, currently there is no cost-effective way of producing nanoemulsions in large scale. The need of subjecting emulsions to an extreme pressure of 50 MPa demands a large excess of energy for the manufacturing process, while low-energy method requires large amount of solvents. Here, nanoemulsions containing a well-characterized hydrophobic drug, carboxyamidotriazole (CAI), are produced in both batch and continuous modes to demonstrate the scalability of nanoemulsion production using Covaris' Adaptive Focused Acoustics™ (AFA) technology. To move from batch scale to continuous flow, the acoustic and thermal energy inputs can be manipulated to adjust particle size, while the composition and temperature of starting materials can be altered to achieve complete dissolution of hydrophobic drugs, thus providing 100% encapsulation efficiency. Furthermore, using two AFA systems in series can drastically enhance the production flow rates, making AFA a competitive means for producing nanoemulsions in the pharmaceutical industry.