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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    • "Alternatively, the morphogenic microenvironment of stem cells can also be engineered via the intrinsic physical properties of biomaterials [11]. The surface chemistry, topography, and stiffness of biomaterials can provide dynamic multiparametric control to instruct emergent cellular behaviors and modulate chondrogenic and osteogenic differentiation [12] [13] [14] [15]. "

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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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    • "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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