Enzyme-controlled, nutritive hydrogel for mesenchymal stromal cell survival and paracrine functions.

Culture-adapted human mesenchymal stromal cells (hMSCs) are appealing candidates for regenerative medicine applications. However, these cells implanted in lesions as single cells or tissue constructs encounter an ischemic microenvironment responsible for their massive death post-transplantation, a major roadblock to successful clinical therapies. We hereby propose a paradigm shift for enhancing hMSC survival by designing, developing, and testing an enzyme-controlled, nutritive hydrogel with an inbuilt glucose delivery system for the first time. This hydrogel, composed of fibrin, starch (a polymer of glucose), and amyloglucosidase (AMG, an enzyme that hydrolyze glucose from starch), provides physiological glucose levels to fuel hMSCs via glycolysis. hMSCs loaded in these hydrogels and exposed to near anoxia (0.1% pO2) in vitro exhibited improved cell viability and angioinductive functions for up to 14 days. Most importantly, these nutritive hydrogels promoted hMSC viability and paracrine functions when implanted ectopically. Our findings suggest that local glucose delivery via the proposed nutritive hydrogel can be an efficient approach to improve hMSC-based therapeutic efficacy.

High throughput micropatterning of interspersed cell arrays using capillary assembly.

A novel technology is reported to immobilize different types of particles or cells on a surface at predefined positions with a micrometric precision. The process uses capillary assembly on arrays of crescent-shaped structures with different orientations. Sequential assemblies in different substrate orientations with different types of particles allow for the creation of imbricated and multiplexed arrays. In this work up to four different types of particles were deterministically localized on a surface. Using this process, antibody coated microparticles were assembled on substrates and used as capture patterns for the creation of complex cell networks. This new technology may have numerous applications in biology, e.g. for fast cell imaging, cell-cell interactions studies, or construction of cell arrays.