Human mesenchymal stem cell differentiation on self-assembled monolayers presenting different surface chemistries

Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Acta biomaterialia (Impact Factor: 5.68). 08/2009; 6(1):12-20. DOI: 10.1016/j.actbio.2009.07.023
Source: PubMed

ABSTRACT Human mesenchymal stem cells (hMSCs) have tremendous potential as a cell source for regenerative medicine due to their capacity for differentiation into a wide range of connective tissue cell types. Although significant progress has been made in the identification of defined growth factor conditions to induce lineage commitment, the effect of underlying biomaterial properties on functional differentiation is far less understood. Here we conduct a systematic assessment of the role for surface chemistry on cell growth, morphology, gene expression and function during hMSC commitment along osteogenic, chondrogenic and adipogenic lineages. Using self-assembled monolayers of omega-functionalized alkanethiols on gold as model substrates, we demonstrate that biomaterial surface chemistry differentially modulates hMSC differentiation in a lineage-dependent manner. These results highlight the importance of initial biomaterial surface chemistry on long-term functional differentiation of adult stem cells, and suggest that surface properties are a critical parameter that must be considered in the design of biomaterials for stem cell-based regenerative medicine strategies.

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    • "Table 2 summarizes the main findings of the described studies. Phillips and co-authors analyzed [14] SAMs functionalized with four different functional groups, namely methyl (–CH 3 ,), hydroxyl (–OH), carboxyl (–COOH) and amino (–NH 2 ), and were able to demonstrate that the surface chemistry has an effect on the pattern of Fn adsorption, which in turn modulates the osteogenic differentiation of human MSCs (hMSCs). Differences in Fn conformation promoted different integrin–ligand interactions and the consequent activation of different intracellular signaling pathways [85]. "
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    ABSTRACT: Human mesenchymal stem cells (MSC) are currently recognized as a powerful cell source for regenerative medicine, notably for their capacity to differentiate into multiple cell types. The combination of MSC with biomaterials functionalized with instructive cues can be used as a strategy to direct specific lineage commitment, and thus improve the therapeutic efficacy of these cells. In terms of biomaterial design, one common approach is the functionalization of materials with ligands capable of directly binding to cell receptors and trigger specific differentiation signaling pathways. Other strategies focus on the use of moieties that have an indirect effect, acting for example as sequesters of bioactive ligands present in the extracellular milieu that will in turn interact with cells. Compared with complex biomolecules, the use of simple compounds such as chemical-moieties, peptides, and other small molecules can be advantageous by leading to less expensive and easily tunable biomaterial formulations. This review describes different strategies that have been used to promote substrate-mediated guidance of osteogenic differentiation of immature osteoblasts, osteoprogenitors and MSC, through chemically conjugated small moieties, both in 2D and 3D set-ups. In each case, the selected moiety the coupling strategy and the main findings of the study were highlighted. The latest advances and future perspectives in the field are also discussed.
    Acta biomaterialia 08/2013; 9(11). DOI:10.1016/j.actbio.2013.08.004 · 5.68 Impact Factor
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    • "The cellular response to biomaterial surfaces, such as attachment and proliferation, is known to be mediated by the material's surface chemistry. Indeed, surface chemistry is also able to instruct cell function and direct cell differentiation [1] [2] [3] [4] [5] [6] [7] [8] [9] [10]. However, it has proven difficult to predict cell fate outcomes based on the molecular structure of the polymer substrate [11] [12]. "
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    ABSTRACT: The control of cell-material interactions is the key to a broad range of biomedical interactions. Gradient surfaces have recently been established as tools allowing the high-throughput screening and optimization of these interactions. In this paper, we show that plasma polymer gradients can reveal the subtle influence of surface chemistry on embryonic stem cell behavior and probe the mechanisms by which this occurs. Lateral gradients of surface chemistry were generated by plasma polymerization of diethylene glycol dimethyl ether on top of a substrate coated with an acrylic acid plasma polymer using a tilted slide as a mask. Gradient surfaces were characterized by X-ray photoelectron spectroscopy, infrared microscopy mapping and profilometry. By changing the plasma polymerization time, the gradient profile could be easily manipulated. To demonstrate the utility of these surfaces for the screening of cell-material interactions, we studied the response of mouse embryonic stem (ES) cells to these gradients and compared the performance of different plasma polymerization times during gradient fabrication. We observed a strong correlation between surface chemistry and cell attachment, colony size and retention of stem cell markers. Cell adhesion and colony formation showed striking differences on gradients with different plasma polymer deposition times. Deposition time influenced the depth of the plasma film deposited and the relative position of surface functional group density on the substrate, but not the range of plasma-generated species.
    Acta biomaterialia 02/2012; 8(5):1739-48. DOI:10.1016/j.actbio.2012.01.034 · 5.68 Impact Factor
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    ABSTRACT: The application of biomaterials to regenerate tissues requires research of the interface between the synthetic material and the living tissue. Because ­biomaterials represent a synthetic extracellular matrix that controls the cell biology by mechanism of cell adhesion, basic mechanisms of cell adhesion are addressed. The technology of designing instructive materials involves chemical modifications by grafting of chemical groups, adhesion ligands and growth factors. Physical characteristics of the materials are created by modifications of the surfaces structure and stiffness of the material. Because stem cells have emerged as promising cells to address the challenge of tissue regeneration the control of stem cells by the characteristic of materials is discussed. Insights into the mechanism at the biointerface that are involved in the regulation of stem cells by materials will advance the development of innovative biomaterials in regenerative medicine.
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