Development of Flexible Cell-Loaded Ultrathin Ribbons for Minimally Invasive Delivery of Skeletal Muscle Cells.

Abstract

Cell transplantation therapy provides a potential solution for treating skeletal muscle disorders, but cell survival after transplantation is poor. This limitation could be addressed by grafting donor cells onto biomaterials to protect them against harsh environments and processing, consequently improving cell viability in situ. Thus, we present here the fabrication of poly(lactic-co-glycolic acid) (PLGA) ultrathin ribbons with "canal-like" structures using a microfabrication technique to generate ribbons of aligned murine skeletal myoblasts (C2C12). We found that the ribbons functionalized with a solution of 3,4-dihydroxy-l-phenylalanine (DOPA) and then coated with poly-l-lysine (PLL) and fibronectin (FN) improve cell attachment and support the growth of C2C12. The viability of cells on the ribbons is evaluated following the syringe-handling steps of injection with different needle sizes. C2C12 cells readily adhere to the ribbon surface, proliferate over time, align (over 74%), maintain high viability (over 80%), and differentiate to myotubes longer than 400 μm. DNA content quantification carried out before and after injection and myogenesis evaluation confirm that cell-loaded ribbons can safely retain cells with high functionality after injection and are suitable for minimally invasive cell transplantation.