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Superposition of nanostructures on microrough titanium-aluminum-vanadium alloy surfaces results in an altered integrin expression profile in osteoblasts.

ABSTRACT: Recent studies of new surface modifications that superimpose well-defined nanostructures on microrough implants, thereby mimicking the hierarchical complexity of native bone, report synergistically enhanced osteoblast maturation and local factor production at the protein level compared to growth on surfaces that are smooth, nanorough, or microrough. Whether the complex micro/nanorough surfaces enhance the osteogenic response by triggering similar patterns of integrin receptors and their associated signaling pathways as with well-established microrough surfaces, is not well understood. Human osteoblasts (hOBs) were cultured until confluent for gene expression studies on tissue culture polystyrene (TCPS) or on titanium alloy (Ti6Al4V) disks with different surface topographies: smooth, nanorough, microrough, and micro/nanorough surfaces. mRNA expression of osteogenesis-related markers such as osteocalcin (BGLAP) and bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2), BMP4, noggin (NOG) and gremlin 1 (GREM1) were all higher on microrough and micro/nanorough surfaces, with few differences between them, compared to smooth and nanorough groups. Interestingly, expression of integrins ?1 and ?2, which interact primarily with collagens and laminin and have been commonly associated with osteoblast differentiation on microrough Ti and Ti6Al4V, were expressed at lower levels on micro/nanorough surfaces compared to microrough ones. Conversely, the ?v subunit, which binds ligands such as vitronectin, osteopontin, and bone sialoprotein among others, had higher expression on micro/nanorough surfaces concomitantly with regulation of the ?3 mRNA levels on nanomodified surfaces. These results suggest that the maturation of osteoblasts on micro/nanorough surfaces may be occurring through different integrin engagement than those established for microrough-only surfaces.

SUBMITTER: Gittens RA

PROVIDER: S-EPMC4287400 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Superposition of nanostructures on microrough titanium-aluminum-vanadium alloy surfaces results in an altered integrin expression profile in osteoblasts.

Gittens Rolando A RA Olivares-Navarrete Rene R Hyzy Sharon L SL Sandhage Kenneth H KH Schwartz Zvi Z Boyan Barbara D BD

Connective tissue research 20140801

Recent studies of new surface modifications that superimpose well-defined nanostructures on microrough implants, thereby mimicking the hierarchical complexity of native bone, report synergistically enhanced osteoblast maturation and local factor production at the protein level compared to growth on surfaces that are smooth, nanorough, or microrough. Whether the complex micro/nanorough surfaces enhance the osteogenic response by triggering similar patterns of integrin receptors and their associat ...[more]

PMID: 25158204

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Project description:Cellular attachment and response to biomaterials are mediated by integrin receptor binding to extracellular matrix proteins adsorbed onto the material surface. Osteoblasts interact with their substrates via several integrin complexes including fibronectin-binding ?5?1 and collagen-binding ?1?1 and ?2?1. Knockdown of ?2 or ?1 integrin subunits inhibits the production of factors that promote an osteogenic microenvironment, including osteocalcin, osteoprotegerin, and TGF?1. Osteoblasts also secrete several angiogenic growth factors such as VEGF-A (VEGF165), FGF-2, and angiopoietin 1, which are regulated by titanium surface topography and surface energy. Here, we examined whether signaling through integrin receptor complexes regulates production and secretion of angiogenic factors during osteoblast differentiation on microtextured Ti surfaces. To do this, integrin subunits ?1, ?2, ?5, and ?1 were stably silenced in MG63 osteoblast-like cells cultured on grit-blasted/acid-etched hydrophobic Ti (SLA) or on hydrophilic SLA (modSLA). VEGF-A production increased in response to Ti surface topography and energy in integrin ?2, ?5, and ?1 silenced cells but decreased in ?1-silenced cells. FGF-2 decreased on modSLA substrates in both ?1 and ?2-silenced cells but was unchanged in response to silencing of either ?5 or ?1. In integrin ?1, ?2, and ?1-silenced cells, Ang-1 increased on modSLA but ?5-silencing did not affect Ang-1 production during surface mediated differentiation. These results suggest that signaling through specific integrin receptor complexes during osteoblast differentiation on microstructured Ti substrates, regulates the production of angiogenic factors by those cells, and this is differentially regulated by surface hydrophilicity. STATEMENT OF SIGNIFICANCE: Successful implantation of synthetic biomaterials into bone depends on the biological process known as osseointegration. Osseointegration is a highly regulated communication of cells that orchestrates the migration of progenitor cells towards the implant site and promotes the deposition and mineralization of extracellular matrix proteins within the implant microenvironment, to tightly join the implant to native bone. In this process, angiogenesis functions as the initiation site of progenitor cell migration and is necessary for matrix deposition by providing the necessary nutrients for bone formation. In the present study, we show a novel regulation of specific angiogenic growth factors by integrin receptor complexes. This research is important to develop biomaterials that promote and maintain osseointegration through proper vascularization and prevent implant failure in patients lacking sufficient angiogenesis.

Project description:Titanium, Aluminum and Vanadium (Ti 6Al 4V) alloy are frequently used as surgical implant but regarding their compatibility in living systems is limited. Ti 6Al 4V was prepared from high purity constituents and Ti 6Al 4V alloy powder (25 mg/ml solvent/Kg body weight) was gavaged to albino mice for 8 days. A saline treated control group was maintained in parallel. A series of behavioral (rota rod, light and dark box, open field and novel object) test performance, complete blood count, selected serum (HDL cholesterol, LDL cholesterol, creatinine, cholesterol and triglycerides) parameters, antioxidant metabolites from vital organs (superoxide dismutase, catalase and lipid peroxidation) from vital organs and body weight were determined in both treatments. It was observed that rota rod test performance in male (P = 0.05) and novel object recognition capability in female mice (P = 0.04) were significantly reduced as compared to their respective control groups. Body weight, complete blood count and studied serum parameters remained unaffected when compared between two treatments of both genders. Concentration of superoxide dismutase in liver (P = 0.008), heart (P = 0.01) and lungs (P = 0.05) was significantly elevated while catalase concentration in liver (P = 0.001) was significantly decreased in female albino mice that were exposed to 25 mg/ml solvent/kg body weight of Ti 6 A l 4 V alloy powder. In case of male albino mice, superoxide dismutase concentration in lungs was reduced (P = 0.05) in mice exposed to Ti 6 A l 4 V alloy powder. In conclusion, our results indicated that short term exposure to 25 mg/ml solvent/Kg body weight of Ti-6Al-4V alloy powder supplementation had adversely affected selected aspects of behavior of albino mice in a gender specific manner. Analysis of antioxidant parameters in vital organs has demonstrated that the applied dose of Ti-6Al-4V alloy powder can disturb the H₂O₂ associated metabolic pathways in albino mice, especially in female mice. As this alloy is part of surgical implants, so we recommend that their effects in living systems must be extensively explored under variable dose and exposure time conditions to know more about their biocompatibility.

Project description:BACKGROUND:Osseointegration is dependent on the implant surface, surrounding bone quality, and the systemic host environment, which can differ in male and female patients. Titanium (Ti) implants with microstructured surfaces exhibit greater pullout strength when compared to smooth-surfaced implants and exhibit enhanced osteogenic cellular responses in vitro. Previous studies showed that 1?,25-dihydroxyvitamin D3 [1?,25(OH)2D3] has a greater effect on rat osteoblast differentiation on microstructured Ti compared to smooth Ti surfaces and tissue culture polystyrene (TCPS). The stimulatory effect of 17?-estradiol (E2) on differentiation is observed in female osteoblasts on micro-rough Ti, but it is not known if male osteoblasts behave similarly in response to E2 and microtopography. This study assessed whether human male and female osteoblasts exhibit sex-specific differences in response to E2 and 1?,25(OH)2D3 when cultured on microstructured Ti surfaces. METHODS:Osteoblasts from three male and three female human donors were cultured on Ti discs with varying surface profiles: a smooth pretreatment (PT), a coarse grit-blasted/acid-etched (SLA), and an SLA surface having undergone modification in a nitrogen environment and stored in saline to maintain hydrophilicity (modSLA). Cells cultured on these surfaces were treated with E2 or 1?,25(OH)2D3. RESULTS:Male and female human osteoblasts responded similarly to microstructure although there were donor-specific differences; cell number decreased, and osteocalcin (OCN), osteoprotegerin (OPG), and latent and active transforming growth factor 1 increased on SLA and modSLA compared to TCPS. Female osteoblasts had higher alkaline phosphatase activity and OCN production than male counterparts but produced less OPG. Both sexes responded similarly to 1?,25(OH)2D3. E2 treatment reduced cell number and increased osteoblast differentiation and factor production only in female cells. CONCLUSIONS:Male and female human osteoblasts respond similarly to microstructure and 1?,25(OH)2D3 but exhibit sexual dimorphism in substrate-dependent responses to E2. E2 affected female osteoblasts, suggesting that signaling is sex-specific and surface-dependent. Donor osteoblasts varied in response, demonstrating the need to test multiple donors when examining human samples. Understanding how male and female cells respond to orthopedic biomaterials will enable greater predictability post-implantation as well as therapies that are more patient-specific.

Dataset Information

Superposition of nanostructures on microrough titanium-aluminum-vanadium alloy surfaces results in an altered integrin expression profile in osteoblasts.

Publications

Superposition of nanostructures on microrough titanium-aluminum-vanadium alloy surfaces results in an altered integrin expression profile in osteoblasts.

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