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      Human mesenchymal stem cell morphology, migration, and differentiation on micro and nano-textured titanium

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          Abstract

          Orthopedic implants rely on facilitating a robust interaction between the implant material surface and the surrounding bone tissue. Ideally, the interface will encourage osseointegration with the host bone, resulting in strong fixation and implant stability. However, implant failure can occur due to the lack of integration with bone tissue or bacterial infection. The chosen material and surface topography of orthopedic implants are key factors that influence the early events following implantation and may ultimately define the success of a device. Early attachment, rapid migration and improved differentiation of stem cells to osteoblasts are necessary to populate the surface of biomedical implants, potentially preventing biofilm formation and implant-associated infection. This article explores these early stem cell specific events by seeding human mesenchymal stem cells (MSCs) on four clinically relevant materials: polyether ether ketone (PEEK), Ti6Al4V (smooth Ti), macro-micro rough Ti6Al4V (Endoskeleton®), and macro-micro-nano rough Ti6Al4V (nanoLOCK®). The results demonstrate the incorporation of a hierarchical macro-micro-nano roughness on titanium produces a stellate morphology typical of mature osteoblasts/osteocytes, rapid and random migration, and improved osteogenic differentiation in seeded MSCs. Literature suggests rapid coverage of a surface by stem cells coupled with stimulation of bone differentiation minimizes the opportunity for biofilm formation while increasing the rate of device integration with the surrounding bone tissue.

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          Highlights

          • We examined effects of hierarchical macro-micro-nano, MMN®, Ti6Al4V on migration, morphology and osteo differentiation.

          • MMN®Ti6Al4V increased the migratory velocity of human mesenchymal stem cells, hMSCs.

          • MMN®Ti6Al4V shifted hMSC morphology from a spindle to a stellate morphology typical of osteoblasts and osteocytes.

          • MMN®Ti6Al4V accelerated osteo differentiation in hMSCs as assessed by alkaline phosphatase and osterix.

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          Most cited references37

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          Local force and geometry sensing regulate cell functions.

          The shapes of eukaryotic cells and ultimately the organisms that they form are defined by cycles of mechanosensing, mechanotransduction and mechanoresponse. Local sensing of force or geometry is transduced into biochemical signals that result in cell responses even for complex mechanical parameters such as substrate rigidity and cell-level form. These responses regulate cell growth, differentiation, shape changes and cell death. Recent tissue scaffolds that have been engineered at the micro- and nanoscale level now enable better dissection of the mechanosensing, transduction and response mechanisms.
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            Geometric cues for directing the differentiation of mesenchymal stem cells.

            Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature-and with each occupying the same area-display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.
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              The interaction of cells and bacteria with surfaces structured at the nanometre scale.

              The current development of nanobiotechnologies requires a better understanding of cell-surface interactions on the nanometre scale. Recently, advances in nanoscale patterning and detection have allowed the fabrication of appropriate substrates and the study of cell-substrate interactions. In this review we discuss the methods currently available for nanoscale patterning and their merits, as well as techniques for controlling the surface chemistry of materials at the nanoscale without changing the nanotopography and the possibility of truly characterizing the surface chemistry at the nanoscale. We then discuss the current knowledge of how a cell can interact with a substrate at the nanoscale and the effect of size, morphology, organization and separation of nanofeatures on cell response. Moreover, cell-substrate interactions are mediated by the presence of proteins adsorbed from biological fluids on the substrate. Many questions remain on the effect of nanotopography on protein adsorption. We review papers related to this point. As all these parameters have an influence on cell response, it is important to develop specific studies to point out their relative influence, as well as the biological mechanisms underlying cell responses to nanotopography. This will be the basis for future research in this field. An important topic in tissue engineering is the effect of nanoscale topography on bacteria, since cells have to compete with bacteria in many environments. The limited current knowledge of this topic is also discussed in the light of using topography to encourage cell adhesion while limiting bacterial adhesion. We also discuss current and prospective applications of cell-surface interactions on the nanoscale. Finally, based on questions raised previously that remain to be solved in the field, we propose future directions of research in materials science to help elucidate the relative influence of the physical and chemical aspects of nanotopography on bacteria and cell response with the aim of contributing to the development of nanobiotechnologies. 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                19 September 2019
                December 2019
                19 September 2019
                : 4
                : 249-255
                Affiliations
                [a ]Department of Biomedical Engineering, The Pennsylvania State University, 122 CBEB Building, University Park, PA, 16802, USA
                [b ]Titan Spine, Inc., Mequon Research Center, 6140 W. Executive Drive, Suite A, Mequon, WI, 53092, USA
                Author notes
                []Corresponding author. justinbrown@ 123456psu.edu
                Article
                S2452-199X(19)30044-1
                10.1016/j.bioactmat.2019.08.001
                6812408
                31667441
                04636619-d1c0-4328-85ab-8cd92f995363
                .

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 29 March 2019
                : 24 July 2019
                : 26 August 2019
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