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In tissue engineering, hMSCs are implanted within a scaffold to provide enhanced capacity for tissue repair. The present study evaluates how mechanical properties of that scaffold can alter the phenotype and genotype of the cells, with the aim of augmenting hMSC differentiation along the myogenic, neurogenic or chondrogenic linages. The hMSCs were grown three\u2010dimensionally (3D) in a hydrogel comprised of poly(ethylene glycol) (PEG)\u2010conjugated to fibrinogen. The hydrogel's shear storage modulus (<jats:italic>G<\/jats:italic>\u2032), which was controlled by increasing the amount of PEG\u2010diacrylate cross\u2010linker in the matrix, was varied in the range of 100\u20132000\u2009Pascal (Pa). The differentiation into each lineage was initiated by a defined culture medium, and the hMSCs grown in the different modulus hydrogels were characterized using gene and protein expression. Materials having lower storage moduli (<jats:italic>G<\/jats:italic>\u2032\u2009=\u2009100\u2009Pa) exhibited more hMSCs differentiating to neurogenic lineages. Myogenesis was favored in materials having intermediate modulus values (<jats:italic>G<\/jats:italic>\u2032\u2009=\u2009500\u2009Pa), whereas chondrogenesis was favored in materials with a higher modulus (<jats:italic>G<\/jats:italic>\u2032\u2009=\u20091000\u2009Pa). Enhancing the differentiation pathway of hMSCs in 3D hydrogel scaffolds using simple modifications to mechanical properties represents an important achievement toward the effective application of these cells in tissue engineering.<\/jats:p>","DOI":"10.1002\/jbm.a.37545","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T09:44:45Z","timestamp":1681724685000},"page":"1441-1458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Modulus\u2010dependent effects on neurogenic, myogenic, and chondrogenic differentiation of human mesenchymal stem cells in three\u2010dimensional hydrogel cultures"],"prefix":"10.1002","volume":"111","author":[{"given":"Revital","family":"Goldshmid","sequence":"first","affiliation":[{"name":"The Faculty of Biomedical Engineering Technion\u2010Israel Institute of Technology  Haifa Israel"},{"name":"The Interdisciplinary Program for Biotechnology 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