(317d) Surface Engineering of Auxetic Scaffolds for Neural and Vascular Differentiation from Human Stem Cells

The complexity and dynamic microenvironments of the extracellular matrix (ECM) can change the interactions with stem cells which can regulate stem cell fate decisions. Stem cells can sense the biophysical and biochemical properties of their microenvironment (such as biomechanical properties andgrowth factors) and transduce the extracellular signaling to the intracellular nuclei to induce gene transcription. Negative Poisson’s Ratio (NPR) (i.e., auxetic) materials have attracted high attention in biomedical applications due to their unique biophysical properties. Poisson’s ratio describes the degree of a material that contracts (or expands) transversally when axially strained, and most materials have Poison’s ratio of 0.3-0.5. The NPR materials also have high porosity, intendent resistance, and shear resistance, which are attractive properties in neurovascular tissue engineering. Human induced pluripotent stem cells (hiPSCs) have the ability to differentiate into all types of cells. The potential applications of hiPSCs include the investigation of neural and vascular tissue degeneration to treat blood-brain barrier dysfunction. In this study, six different polyurethane auxetic foams with different modulus (700-2700 Pa) and Poisson’s ratio (-0.3 to -0.5) were fabricated and characterized to study the hiPSC lineage-specific differentiations. The biocompatibility of the foams was regulated by modifying the surfaces with chitosan and heparin. Chitosan modified foams were shown to promote cell viability. Then, the vascular and neural differentiation of hiPSCs on different foams with distinct elastic modulus and Poisson’s ratio were investigated. Heparin modification can prompte endothelial and neural differentiation. In the foam with modulus of 365 ± 50 Pa and Poisson’s ratio of –0.196, the neural specific markers were mostly expressed when cultured with the chitosan-modified scaffolds. In addition, endothelial cell-specific markers CD31 and ZO-1 were mostly expressed in the foam with modulus of 1400 Pa and Poisson’s ratio of -0.297. This study has significance in understanding biophysical regulation of human pluripotent stem cell fate decisions and in establishing 3-D neurovascular tissue models for drug screening and neurological disease modeling.