title: The effects of interactive mechanical and biochemical niche signaling on osteogenic differentiation of adipose-derived stem cells using combinatorial hydrogels.
abstract: Stem cells reside in a multi-factorial environment containing biochemical and mechanical signals. Changing biochemical signals in most scaffolds often leads to simultaneous changes in mechanical properties, which makes it difficult to elucidate the complex interplay between niche cues. Combinatorial studies on cell-material interactions have emerged as a tool to facilitate analyses of stem cell responses to various niche cues, but most studies to date have been performed on two-dimensional environments. Here we developed three-dimensional combinatorial hydrogels with independent control of biochemical and mechanical properties to facilitate analysis of interactive biochemical and mechanical signaling on adipose-derived stem cell osteogenesis in three dimensions. Our results suggest that scaffold biochemical and mechanical signals synergize only at specific combinations to promote bone differentiation. Leading compositions were identified to have intermediate stiffness (∼55kPa) and low concentration of fibronectin (10μg ml(-1)), which led to an increase in osteocalcin gene expression of over 130-fold. Our results suggest that scaffolds with independently tunable niche cues could provide a powerful tool for conducting mechanistic studies to decipher how complex niche cues regulate stem cell fate in three dimensions, and facilitate rapid identification of optimal niche cues that promote desirable cellular processes or tissue regeneration.
authors.affiliation: Program of Material Science and Engineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Nii
authors.forename: Janice H
authors.initials: JH
authors.lastname: Lai
authors.forename: Michael
authors.initials: M
authors.lastname: Keeney
authors.forename: Li-Hsin
authors.initials: LH
authors.lastname: Han
authors.forename: Anthony
authors.initials: A
authors.lastname: Behn
authors.forename: Galym
authors.initials: G
authors.lastname: Imanbayev
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000880:Anthraquinones / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D019245:Compressive Strength / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D055595:Mechanical Phenomena / Q000187:drug effects*; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013194:Staining and Labeling; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000880:Anthraquinones; D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II; D006576:Heterocyclic Compounds, 4 or More Rings; D020100:Hydrogels; D015675:Osteocalcin; C472645:blebbistatin; C010078:alizarin; D024501:Nonmuscle Myosin Type IIB; D002118:Calcium