Direct and indirect effects of microstructured titanium substrates on the induction of mesenchymal stem cell differential towards the osteoblast lineage

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332-0363, USA.
Biomaterials (Impact Factor: 8.56). 04/2010; 31(10):2728-35. DOI: 10.1016/j.biomaterials.2009.12.029
Source: PubMed


Microstructured and high surface energy titanium substrates increase osseointegration in vivo. In vitro, osteoblast differentiation is increased, but effects of the surface directly on multipotent mesenchymal stem cells (MSCs) and consequences for MSCs in the peri-implant environment are not known. We evaluated responses of human MSCs to substrate surface properties and examined the underlying mechanisms involved. MSCs exhibited osteoblast characteristics (alkaline phosphatase, RUNX2, and osteocalcin) when grown on microstructured Ti; this effect was more robust with increased hydrophilicity. Factors produced by osteoblasts grown on microstructured Ti were sufficient to induce co-cultured MSC differentiation to osteoblasts. Silencing studies showed that this was due to signaling via alpha2beta1 integrins in osteoblasts on the substrate surface and paracrine action of secreted Dkk2. Thus, human MSCs are sensitive to substrate properties that induce osteoblastic differentiation; osteoblasts interact with these surface properties via alpha2beta1 and secrete Dkk2, which acts on distal MSCs.

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Available from: Sharon L Hyzy, Oct 01, 2015
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    • "Previous studies in our lab confirm that the combined presence of micro-/submicronscale roughness contributes to increased osteoblast response [10] [11]. By altering only the surface microtopography and without exogenous factors in media, osteoblast differentiation can be increased on titanium surfaces [12]. This may be due in part to the protein–material interaction at the surface, which affects downstream cell response. "
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    ABSTRACT: Additive manufacturing by laser sintering is able to produce high resolution metal constructs for orthopedic and dental implants. In this study, we used a human trabecular bone template to design and manufacture Ti-6Al-4V constructs with varying porosity via laser sintering. Characterization of constructs revealed interconnected porosities ranging from 15–70% with compressive moduli of 2579–3693 MPa. These constructs with macro porosity were further surface-treated to create a desirable multi-scale micro-/nano-roughness, which has been shown to enhance the osseointegration process. Osteoblasts (MG63 cells) exhibited high viability when grown on the constructs. Proliferation (DNA) and alkaline phosphatase specific activity, an early differentiation marker, decreased as porosity increased, while osteocalcin, a late differentiation marker, as well as osteoprotegerin, vascular endothelial growth factor and bone morphogenetic proteins 2 and 4 increased with increasing porosity. Three-dimensional (3D) constructs with the highest porosity and surface modification supported the greatest osteoblast differentiation and local factor production. These results indicate that additively manufactured 3D porous constructs mimicking human trabecular bone and produced with additional surface treatment can be customized for increased osteoblast response. Increased factors for osteoblast maturation and differentiation on high porosity constructs suggest the enhanced performance of these surfaces for increasing osseointegration in vivo.
    Biofabrication 10/2014; 6(4):045007. DOI:10.1088/1758-5082/6/4/045007 · 4.29 Impact Factor
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    • "Since the process of osteointegration occurs at the interface between the implant and bone tissue, the technology of surface modification has been proposed to improve the osteointegration of the implant, such as through sand blasting [11], acid and alkali treatment [12] [13], bioactive coating of bioceramics [14], and electrochemical oxidation [15] [16]. In the past, studies regarding the technology of surface modification were primarily evaluated based on the influence of surface topography of implants on cellular response at the micrometer scale [17] [18] [19]. However, in recent years, much research attention has been given to surface modification in the nanoscale regime [20] [21] [22]. "
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    ABSTRACT: Titanium dioxide (TiO2) nanowire surface structures were fabricated in situ by a thermal oxidation process, and their ability to enhance the osteogenic potential of primary osteoblasts was investigated. Human osteoblasts were isolated from nasal bone and cultured on a TiO2 nanowires coated substrate to assess its in vitro cellular interaction. Bare featureless Ti-6Al-4V substrate was used as a control surface. Initial cell adhesion, cell proliferation, cell differentiation, cell mineralization, and osteogenic related gene expression were examined on the TiO2 nanowire surfaces as compared to the control surfaces after 2 weeks of culturing. Cell adhesion and cell proliferation were assayed by field emission scanning electron microscope (FESEM) and Alamar Blue reduction assay, respectively. The nanowire surfaces promoted better cell adhesion and spreading than the control surface, as well as leading to higher cell proliferation. Our results showed that osteoblasts grown onto the TiO2 nanowire surfaces displayed significantly higher production levels of alkaline phosphatase (ALP), extracellular (ECM) mineralization and genes expression of runt-related transcription factor (Runx2), bone sialoprotein (BSP), ostoepontin (OPN) and osteocalcin (OCN) compared to the control surfaces. This suggests the potential use of such surface modification on Ti-6Al-4V substrates as a promising means to improve the osteointegration of titanium based implants.
    Applied Surface Science 09/2014; 320:161–170. DOI:10.1016/j.apsusc.2014.08.160 · 2.71 Impact Factor
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    • "Micron scale topographies have been shown to influence the lineage-specific differentiation of MSCs [21] [22] [26], and further studies are looking to increase cellular response and control. The recent emergence of the use of nanotopographies to control and enhance the differentiation of MSCs holds great potential in the fields of both orthopaedics and dentistry. "
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    ABSTRACT: Stem cells continue to receive widespread attention due to their potential to revolutionise treatments in the fields of both tissue engineering and regenerative medicine. Adult stem cells, specifically mesenchymal stromal cells (MSCs), play a vital role in the natural events surrounding bone healing and osseointegration through being stimulated to differentiate along their osteogenic lineage and in doing so, they form new cortical and trabecular bone tissue. Understanding how to control, manipulate, and enhance the intrinsic healing events modulated through osteogenic differentiation of MSCs by the use of modified surfaces and biomaterials could potentially advance the fields of both orthopaedics and dentistry. This could be by either using surface modification to generate greater implant stability and more rapid healing following implantation or the stimulation of MSCs ex vivo for reimplantation. This review aims to gather publications targeted at promoting, enhancing, and controlling the osteogenic differentiation of MSCs through biomaterials, nanotopographies, and modified surfaces for use in implant procedures.
    Stem cell International 05/2013; 2013(5557):361637. DOI:10.1155/2013/361637 · 2.81 Impact Factor
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