Article

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

ABSTRACT

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.

Download full-text

Full-text

Available from: Sharon L Hyzy
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: For more than 100 years, cells and tissues have been studied in vitro using glass and plastic surfaces. Over the last 10–20 years, a great body of research has shown that cells are acutely sensitive to their local environment (extracellular matrix, ECM) which contains both chemical and physical cues that influence cell behavior. These observations suggest that modern cell culture systems, using tissue culture polystyrene (TCP) surfaces, may fail to reproduce authentic cell behavior in vitro, resulting in “artificial outcomes.” In the current study, we use bone marrow (BM)- and adipose (AD)-derived stromal cells to prepare BM-ECM and AD-ECM, which are decellularized after synthesis by the cells, to mimic the cellular niche for each of these tissues. Each ECM was characterized for its ability to affect BM- and AD-mesenchymal stem cell (MSC) proliferation, as well as proliferation of three cancer cell lines (HeLa, MCF-7, and MDA-MB-231), modulate cell spreading, and direct differentiation relative to standard TCP surfaces. We found that both ECMs promoted the proliferation of MSCs, but that this effect was enhanced when the tissue-origin of the cells matched that of the ECM (i.e. BM-ECM promoted the proliferation of BM-MSCs over AD-MSCs, and vice versa). Moreover, BM- and AD-ECM were shown to preferentially direct MSC differentiation towards either osteogenic or adipogenic lineage, respectively, suggesting that the effects of the ECM were tissue-specific. Further, each ECM influenced cell morphology (i.e. circularity), irrespective of the origin of the MSCs, lending more support to the idea that effects were tissue specific. Interestingly, unlike MSCs, these ECMs did not promote the proliferation of the cancer cells. In an effort to further understand how these three culture substrates influence cell behavior, we evaluated the chemical (protein composition) and physical properties (architecture and mechanical) of the two ECMs. While many structural proteins (e.g. collagen and fibronectin) were found at equivalent levels in both BM- and AD-ECM, the architecture (i.e. fiber orientation; surface roughness) and physical properties (storage modulus, surface energy) of each were unique. These results, demonstrating differences in cell behavior when cultured on the three different substrates (BM- and AD-ECM and TCP) with differences in chemical and physical properties, provide evidence that the two ECMs may recapitulate specific elements of the native stem cell niche for bone marrow and adipose tissues. More broadly, it could be argued that ECMs, elaborated by cells ex vivo, serve as an ideal starting point for developing tissue-specific culture environments. In contrast to TCP, which relies on the “one size fits all” paradigm, native tissue-specific ECM may be a more rational model to approach engineering 3D tissue-specific culture systems to replicate the in vivo niche. We suggest that this approach will provide more meaningful information for basic research studies of cell behavior as well as cell-based therapeutics.
    No preview · Article · Jan 2016 · Matrix biology: journal of the International Society for Matrix Biology
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Statement of significance: Directing stem cell differentiation and morphogenesis via biomaterials represents a novel strategy to promote cell fates and tissue formation. Our study demonstrates the ability of calcium phosphate-based mineral particles to promote osteochondrogenic differentiation of embryonic stem cell aggregates as well as modulate teratoma formation in vivo. This hybrid biomaterial-ESC aggregate approach serves as an enabling platform to evaluate the ability of biomaterials to regulate stem cell fate and regenerate functional skeletal tissues for clinical applications.
    No preview · Article · Oct 2015 · Acta biomaterialia
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: As an FDA-approved implantable material, carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses excellent mechanical properties similar to those of human cortical bone and is a prime candidate to replace conventional metallic implants. The bioinertness and inferior osteogenic properties of CFRPEEK, however, limit its clinical application as orthopedic/dental implants. The present work aimed at developing a novel carbon fiber-reinforced polyetheretherketone-nanohydroxyapatite (PEEK/CF/n-HA) ternary biocomposite with micro/nano-topographical surface for the enhancement of the osteogenesis as a potential bioactive material for bone grafting and bone tissue-engineering applications. The combined modification of oxygen plasma and sand-blasting could improve the hydrophily and generate micro/nano-topographical structures on the surface of the CFRPEEK-based ternary biocomposite. The results clearly showcased that the micro-/nano-topographical PEEK/n-HA/CF ternary biocomposite demonstrated the outstanding ability to promote the proliferation and differentiation of MG-63 cells in vitro as well as to boost the osseointegration between implant and bone in vivo, thereby boding well application to bone tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.
    Full-text · Article · Mar 2015 · Materials Science and Engineering C
Show more