AVS 53rd International Symposium
    Biomaterial Interfaces Wednesday Sessions
       Session BI-WeA

Paper BI-WeA3
Tunable Interfacial Hydrogels for Control of Neural Stem Cell Fate

Wednesday, November 15, 2006, 2:40 pm, Room 2014

Session: Bio-Interfacial Modification and Bio-Immobilization II (Honoring Marcus Textor, ETH-Zürich for Substantial Contributions to the Field)
Presenter: K. Saha, University of California, Berkeley
Authors: K. Saha, University of California, Berkeley
E.F. Irwin, University of California, Berkeley
D.V. Schaffer, University of California, Berkeley
K.E. Healy, University of California, Berkeley
Correspondent: Click to Email
Highly-regulated signals in the stem cell microenvironment, such as growth factor presentation and concentration, and matrix mechanical stiffness, have been implicated in modulating stem cell proliferation and maturation. However, tight control of proliferation and lineage commitment signals is rarely achieved during growth outside the body, since the spectrum of biochemical and mechanical signals that govern stem cell self-renewal and maturation are not fully understood. Therefore, stem cell control can potentially be enhanced through the development of material platforms that more precisely orchestrate the presentation of the aforementioned signals to stem cells. Using a biomimetic interpenetrating polymer network (IPN), we define a robust synthetic and fully mechanically and chemically defined platform to regulate stem cell number and differentiation for the culture of adult neural stem cells. The IPN's properties, such as ligand type, ligand surface density, and stiffness (i.e., complex modulus 1-10 kPa), were quantitatively controlled and characterized. In this work, hydrogels modified with two cell-binding ligands, CGGNGEPRGDTYRAY from bone sialoprotein [bsp-RGD(15)] and CSRARKQAASIKVAVSADR from laminin [lam-IKVAV(19)], were assayed for their ability to regulate self-renewal and differentiation of neural stem cells in a dose-dependent manner. Media conditions, supplemented with particular soluble factors, were modulated for either stem cell self-renewal or differentiation. IPNs with bsp-RGD(15) above 5.3 pmol.cm@super-2@ supported both self-renewal and differentiation, whereas hydrogels with lam-IKVAV(19) failed to support stem cell adhesion and did not influence early differentiation. This platform is highly tunable and could potentially be used to translate in vitro control of stem cells to an implantable biomaterial that can be harnessed for tissue regeneration.