Abstract
Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.
Highlights
Fate and function of stem cells are controlled by adhesive interactions with the extracellular matrix mediated by adhesion receptors, like integrins [1]
Cartilage or other tissues of the mesenchyme after injury or disease a suitable scaffold incorporated at the site of injury in vivo could provide components of a stem cell niche that promote the activity of mesenchymal stem cells (MSC) which can be transplanted together with a scaffold or recruited from bone marrow
First we have been interested whether homogeneously immobilized fibronectin differentially regulate mechanisms of cell adhesion and the organization of cytoskeletal structures compared to a glass surface as control
Summary
Fate and function of stem cells are controlled by adhesive interactions with the extracellular matrix mediated by adhesion receptors, like integrins [1]. The design of a material that serves as a substrate for cells and determines survival, proliferation, differentiation, and migration is a great challenge for application in regenerative medicine. Beside of the type of extracellular matrix or components of matrix proteins, designing defined topographies as adhesive substrate to control cell shape has demonstrated the commitment of MSC to develop to an adipocyte or osteoblast [2]. Nanofeatures of surface topographies, differing in ordered or disordered patterns controlled the differentiation of MSC to osteoblasts or facilitated self-renewal [3,4,5]. The controlled guidance of stem cell migration by a material surface would have significant implications for regenerative medicine. Stimulation of migration can disperse the stem cells, which have been transplanted into the body to the surrounding tissue for regeneration. Materials could be used to stimulate the recruitment of stem cells, which already exist in the body to the desired anatomic site
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