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Hydrogels possess low modulus, and they are suitable as substrates for neuronal differentiation of stem cells. Alternatively, polymers with low modulus might be appropriate for this purpose. Within the category of the neuronal tissue structures, selleck products glial differentiation of stem cells might be gained on stiffer scaffolds, and neural differentiation can be achieved on softer scaffolds. By fine tuning the stiffness of the matrix, there is a great possibility to control the differentiation of stem cells into appropriate nerve cells. Cardio-vascular Lineage commitment of MSCs towards specific vascular cells (MSCs to ECs or MSCs to SMCs) on electrospun scaffolds could be manipulated by controlling the substrate modulus, from 2 to 15 kPa. Around 95% of MSCs seeded on soft scaffolds (3 kPa) showed Flk-1 endothelial markers within 24 h, while only 20% of MSCs seeded on the rigid scaffolds (> 8 kPa) showed Flk-1 marker. In contrast, about 80% of MSCs seeded on rigid scaffolds (> 8 kPa) showed smooth muscle ��-actin marker within 24 h, while fewer than 10% of MSCs seeded on soft scaffold (S6 Kinase effect of scaffold elasticity and growth factors has been studied for the differentiation of MSCs. In one such study, MSCs were seeded on soft nanofibrousmatrices with or without VEGF, and in Petri dishes with or without VEGF, where these researchers found that MSCs in soft matrices Lapatinib clinical trial with VEGF showed significant increase in the expression of endothelia markers (vWF, eNOS, Flt-1, and Flk-1), with faster up-regulation of the endothelial markers. The results indicate that it is critical to control both mechanical factors and biochemical factors to regulate vascular endothelial regeneration of MSCs[116]. MSCs gained very low rate of cardiogenic differentiation after transplantation to infarcted heart, partly because stiffer scar tissue lack the capacity to support cardiogenic differentiation. Thermosensitive and injectable hydrogels with different moduli (16, 45 and 65 kPa) were achieved by controlling the concentration of the hydrogel solution. After 14 d, more than 76% MSCs differentiated into cardiac cells in gels with 45 and 65 kPa, while MSCs in the 65 kPa gel had the highest differentiation efficiency[117]. But the effect of stiffness towards the differentiation of stem cells might be time-dependent. Human embryonic stem cells are sensitive to substrate stiffness during early mesodermal specification, but not late fate choices during cardiac differentiation, when they are seeded on polyacrylamide hydrogels. An intermediate stiffness was most beneficial for cardiomyogenic differentiation than soft or stiff substrates[118].