Biomaterials for Cellular Reprogramming and Origami-Based Tissue Engineering

Lineage conversion from one somatic cell type to another is an attractive approach for deriving specific therapeutic cell generation. We report the development of a direct conversion methodology in which cells are transdifferentiated through a plastic intermediate state induced by exposure to non-integrative minicircle DNA (MCDNA)-based reprogramming factors, followed by differentiation into myoblasts. In order to increase the MCDNA delivery efficiency, reprogramming factors were delivered into the chondrocytes via electroporation followed by poly (β-amino esters) (PBAE) transfection. We used this approach to convert human chondrocytes to myoblast, and with treatment of SB-431542, an inhibitor of the activin receptor-like kinase receptors, to enhance myogenic commitment. Differentiated cells exhibited expression of myogenic markers such as MyoD and Myog. This methodology for direct lineage conversion from chondrocytes to myoblast represents a novel non-viral Method to convert hard-to-transfect cells to other lineage. Furthermore, we present a novel method for assembling biofunctionalized paper into a 3-dimensionally (3D) structured complex scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) (PSMa) layer via initiated chemical vapor deposition (iCVD) followed by the immobilization of poly-L-lysine (PLL) and deposition of Ca²⁺. This procedure ensures the formation of alginate hydrogel on the paper due to Ca²⁺ diffusion. Finally, we show that the paper-based scaffold can be folded freely into 3D tissue-like structures by simple origami-based method.