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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    • "21 culture substrates or tissue engineering scaffold materials69707172. As culture substrates/scaffolds are often designed to favor various types of electrostatic interactions that influence protein/solute adsorption and ultimately modulate cell attachment, spreading, and differentiation[32,55,58,66676873,74], it is likely that the observed differences in surface energy between TCP, BM-and AD-ECM play a role in determining stem cell fate when cultured on these substrates. In summary, the present study provides evidence indicating that native ECM (BM-ECM and AD-ECM), produced ex vivo, replicated the tissue-specific microenvironment (niche) of BM-MSCs and AD-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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    • "e l s e v i e r . c o m / l o c a t e / m s e c Surface topographical modifications of implant at micrometer scale, such as those that are induced by acid etching or sand-blasting, have been used effectively to enhance osteoblastic lineage cell differentiation in vitro [12] and osseointegration in vivo [13], and have been clinically [14] compared to smoother surfaces. Currently, the addition of nanostructures onto implant interfaces such as plasma treatment, to better mimic the hierarchical structure of the bone, has also shown promising results in vitro [15] [16] [17] and in vivo [18], validating the biological relevance of nanotopography for bone formation. "
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