Article

Engineering the cell-material interface for controlling stem cell adhesion, migration, and differentiation

Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, MC 0412, La Jolla, CA 92093, United States.
Biomaterials (Impact Factor: 8.31). 03/2011; 32(15):3700-11. DOI: 10.1016/j.biomaterials.2011.02.004
Source: PubMed

ABSTRACT The effective utilization of stem cells in regenerative medicine critically relies upon our understanding of the intricate interactions between cells and their extracellular environment. While bulk mechanical and chemical properties of the matrix have been shown to influence various cellular functions, the role of matrix interfacial properties on stem cell behavior is unclear. Here, we report the striking effect of matrix interfacial hydrophobicity on stem cell adhesion, motility, cytoskeletal organization, and differentiation. This is achieved through the development of tunable, synthetic matrices with control over their hydrophobicity without altering the chemical and mechanical properties of the matrix. The observed cellular responses are explained in terms of hydrophobicity-driven conformational changes of the pendant side chains at the interface leading to differential binding of proteins. These results demonstrate that the hydrophobicity of the extracellular matrix could play a considerably larger role in dictating cellular behaviors than previously anticipated. Additionally, these tunable matrices, which introduce a new control feature for regulating various cellular functions offer a platform for studying proliferation and differentiation of stem cells in a controlled manner and would have applications in regenerative medicine.

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    • "Cell interactions with their surrounding extracellular matrix (ECM) play an important role in regulating cellular functions as basic as proliferation [1] [2] and as complex as stem cell differentiation [3e5]. It has become widely appreciated that the properties of this cell-ECM interface, including surface topography [6] [7], hydrophobicity and hydrophilicity [8], and surface chemistry [4] [7] [9], must mimic those of native ECM to appropriately guide cell function. Spatial and temporal patterns of these cues are equally important in regulating function [10]. "
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    Biomaterials 06/2015; 52:140. DOI:10.1016/j.biomaterials.2015.01.034
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    • "PEGDA (M n = 3.4 kDa) and N-acryloyl 6-aminocaproic acid (A6ACA) were synthesized as previously described [17] [33] [34]. "
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    • "However , cell adhesion and migration, crucial to attain successful results for both strategies and mediated by receptor–ligand interactions at the cell–material interface, are features that are not naturally demonstrated by traditional hydrogels. This behavior has been attributed to hydrogel's extreme hydrophilicity, which per se allows water molecules to bind to the polymer backbone [4] [5], as well as to negatively charged polymers [6] [7] that repulse cells, both limiting the adsorption of cell-adhesive proteins prior to cell attachment [8]. A common strategy to overcome the absence of cell adhesion within non-adhesive polymer hydrogels relies on the combination with extracellular matrix (ECM) glycoproteins [9] [10] [11], or the covalent bond of glycoprotein peptide sequences [12] [13] [14] [15], capable of binding to cellular membrane receptors. "
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    ABSTRACT: The resemblance between soft tissue's extracellular matrix (ECM) and hydrogels, characterized by high water content viscoelastic polymeric networks, have been sustaining hydrogel's advances for Tissue Engineering and Regenerative Medicine (TERM) purposes. Current research on hydrogels has been focusing on introducing cell-adhesive peptides to promote cell adhesion and spreading, a critical applicability limitation. Here we report the development of gellan gum (GG) spongy-like hydrogels with ameliorated mechanical performance and flexibility in relation to hydrogels, using a simple and cost-effective method. Most importantly, these materials allow the entrapment of different cell types representing mesenchymal, epidermal and osteoblastic phenotypes that spread within the 3D microstructure. This effect was associated to microstructural rearrangements characterized by pore wall thickening and pore size augmentation, and lower water content than precursor hydrogels. These properties significantly affected protein adsorption once cell adhesion was inhibited in the absence of serum. Spongy-like hydrogels are not adhesive for endothelial cells however this issue was surpassed by a pre-incubation with a cell-adhesive protein, as demonstrated for other substrates but not for traditional hydrogels. The proposed cell-compatible GG-based structures avoid time-consuming and expensive strategies that have been used to include cell-adhesive features to traditional hydrogels. This, associated to their off-the-shelf availability in an intermediary dried state represent unique and highly relevant features for diverse TERM applications.
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