A: alizarin red staining, partly coated NiTi-sheet (coated part indicated by arrow, border indicated by dot line); scale bar 2 mm. B: detail of A, uncoated part; scale bar 200 µm. C: detail of A, coated part; scale bar 200 µm. D: NiTi-nanocoated structure with osteogenic ASCs; green: osteocalcin (indicated by arrows), blue: nuclei; scale bar 50 µm.

A: alizarin red staining, partly coated NiTi-sheet (coated part indicated by arrow, border indicated by dot line); scale bar 2 mm. B: detail of A, uncoated part; scale bar 200 µm. C: detail of A, coated part; scale bar 200 µm. D: NiTi-nanocoated structure with osteogenic ASCs; green: osteocalcin (indicated by arrows), blue: nuclei; scale bar 50 µm.

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Autologous cells can be used for a bioactivation of osteoimplants to enhance osseointegration. In this regard, adipose derived stem cells (ASCs) offer interesting perspectives in implantology because they are fast and easy to isolate. However, not all materials licensed for bone implants are equally suited for cell adhesion. Surface modifications a...

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... Nitinol nanoparticles (NiTi), composed of nickel and titanium, were initially utilized in the aerospace industry to resist heat and fatigue in missile nose cones [12]. NiTi has low toxicity, corrosion resistance, superelasticity, and biocompatibility, making them promising candidates for coatings on reconstructive surgery implants [13,14]. A NiTi surface coating also has a high potential for additional biomedical applications in stents, equipment and tools, staples, and dental wires [3,4,[15][16][17][18][19][20][21][22][23]. ...
Article
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The challenges facing metallic implants for reconstructive surgery include the leaching of toxic metal ions, a mismatch in elastic modulus between the implant and the treated tissue, and the risk of infection. These problems can be addressed by passivating the metal surface with an organic substrate and incorporating antibiotic molecules. Nitinol (NiTi), a nickel-titanium alloy, is used in devices for biomedical applications due to its shape memory and superelasticity. However, unmodified NiTi carries a risk of localized nickel toxicity and inadequately supports angiogenesis or neuroregeneration due to limited cell adhesion, poor biomineralization, and little antibacterial activity. To address these challenges, NiTi nanoparticles were modified using self-assembled phosphonic acid monolayers and functionalized with the antibiotics ceftriaxone and vancomycin via the formation of an amide. Surface modifications were monitored to confirm that phosphonic acid modifications were present on NiTi nanoparticles and 100% of the samples formed ordered films. Modifications were stable for more than a year. Elemental composition showed the presence of nickel, titanium, and phosphorus (1.9% for each sample) after surface modifications. Dynamic light scattering analysis suggested some agglomeration in solution. However, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy confirmed a particle size distribution of <100 nm, the even distribution of nanoparticles on coverslips, and elemental composition before and after cell culture. B35 neuroblastoma cells exhibited no inhibition of survival and extended neurites of approximately 100 μm in total length when cultured on coverslips coated with only poly-l-lysine or with phosphonic acid-modified NiTi, indicating high biocompatibility. The ability to support neural cell growth and differentiation makes modified NiTi nanoparticles a promising coating for surfaces in metallic bone and nerve implants. NiTi nanoparticles functionalized with ceftriaxone inhibited Escherichia coli and Serratia marcescens (SM6) at doses of 375 and 750 μg whereas the growth of Bacillus subtilis was inhibited by a dose of only 37.5 μg. NiTi-vancomycin was effective against B. subtilis at all doses even after mammalian cell culture. These are common bacteria associated with infected implants, further supporting the potential use of functionalized NiTi in coating reconstructive implants.
... 10 ASC can differentiate to form bone, cartilage, muscle or fat tissue as well as various other cell types, representing an auspicious perspective for tissue engineering applications. [11][12][13] Due to their favorable secretion profile of growth factors and cytokines, ASC showed a highly regenerative potential in pre-clinical and clinical settings. 14,15 It was described earlier that ASC also enhance vascularization in de-novo tissue formation. ...
Article
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Human cartilage tissue remains a challenge for the development of therapeutic options due to its poor vascularization and reduced regenerative capacities. There are a variety of research approaches dealing with cartilage tissue engineering. In addition to different biomaterials, numerous cell populations have been investigated in bioreactor-supported experimental setups to improve cartilage tissue engineering. The concept of the present study was to investigate spider silk cocoons as scaffold seeded with adipose-derived stromal cells (ASC) in a custom-made bioreactor model using cyclic axial compression to engineer cartilage-like tissue. For chemical induction of differentiation, BMP-7 and TGF-β2 were added and changes in cell morphology and de-novo tissue formation were investigated using histological staining to verify chondrogenic differentiation. By seeding spider silk cocoons with ASC, a high colonization density and cell proliferation could be achieved. Mechanical induction of differentiation using a newly established bioreactor model led to a more roundish cell phenotype and new extracellular matrix formation, indicating a chondrogenic differentiation. The addition of BMP-7 and TGF-β2 enhanced the expression of cartilage specific markers in immunohistochemical staining. Overall, the present study can be seen as pilot study and valuable complementation to the published literature.
... 17,18 In addition, it was reported almost no degradation for Nitinol, and the relatively high stiffness of titanium can cause stress shielding and thus implant loosening. 19,20 Despite all, it has unique properties, shape memory effect, and superelasticity, which is described below. 21,22 Shape memory effect ...
Article
Isoatomic NiTi alloy (Nitinol) has become an important biomaterial due to its unique characteristics, including shape memory effect, superelasticity, and high damping. Nitinol has been widely used in the biomedical field, including orthopedics, vascular stents, orthodontics, and other medical devices. However, there have been convicting views about the bio-compatibility of Nitinol. Some studies have shown that Nitinol has extremely low cytotoxicity, indicating Nitinol has good biocompatibility. However, some studies have shown that the in-vivo corrosion resistance of Nitinol significantly decreases. This comprehensive paper discusses the historical developments of Nitinol, its biomedical applications, and its specific functional property. These render the suitability of Nitinol for such biomedical applications and provide insights into its in vivo and in vitro biocompatibility in the physiological environment and the antimicrobial strategies that can be applied to enhance its biocompatibility. Although 3D metal printing is still immature and Nitinol medical materials are difficult to be processed, Nitinol biomaterials have excellent potential and commercial value for 3D printing. However, there are still significant problems in the processing of Nitinol and improving its biocompatibility. With the deepening of research and continuous progress in surface modification and coating technology, a series of medical devices made from Nitinol are expected to be released soon.
... Nanoparticles are currently considered one of the most powerful tools in nanomedicine applications [14,18,19,24,[70][71][72][73][74][75]. Therefore, the research advancement is mainly focused on the improvement of the efficacy of NPs by (i) developing NPs with different biomaterials, different sizes, and different chemical functionalization [46,[76][77][78]; (ii) evaluating their biological effects, comparing the naked and functionalized characteristics. These aspects are mandatory for regenerative medicine applications, but, up to now, studies on stem cells and NPs are still scarce and contradictory. ...
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The biomedical translational applications of functionalized nanoparticles require comprehensive studies on their effect on human stem cells. Here, we have tested neat star-shaped mesoporous silica nanoparticles (s-MSN) and their chemically functionalized derivates; we examined nanoparticles (NPs) with similar dimensions but different surface chemistry, due to the amino groups grafted on silica nanoparticles (s-MSN-NH2), and gold nanoseeds chemically adsorbed on silica nanoparticles (s-MSN-Au). The different samples were dropped on glass coverslips to obtain a homogeneous deposition differing only for NPs’ chemical functionalization and suitable for long-term culture of human Bone Marrow–Mesenchymal stem cells (hBM-MSCs) and Adipose stem cells (hASCs). Our model allowed us to demonstrate that hBM-MSCs and hASCs have comparable growth curves, viability, and canonical Vinculin Focal adhesion spots on functionalized s-MSN-NH2 and s-MSN-Au as on neat s-MSN and control systems, but also to show morphological changes on all NP types compared to the control counterparts. The new shape was stem-cell-specific and was maintained on all types of NPs. Compared to the other NPs, s-MSN-Au exerted a small genotoxic effect on both stem cell types, which, however, did not affect the stem cell behavior, likely due to a peculiar stem cell metabolic restoration response.
... (Farraro et al., 2014;Kim et al., 2017;Li et al., 2018;Liu et al., 2014;Nabiyouni et al., 2018;Yazdimamaghani et al., 2017;Yazdimamaghani et al., 2015;Alvarez and Nakajima, 2009;Bose et al., 2012;Jamil et al., 2015;Jonitz et al., 2011;Shimko et al., 2005;Chen et al., 2017a;Haugen et al., 2013;Kim et al., 2016a;Liu et al., 2017;Takizawa et al., 2018;Hanawa, 2010;Gotman et al., 2013;Habijan et al., 2013;Hoffmann et al., 2014;Strauß et al., 2013) Brittle Slow degradation except TCP-excessive dissolution,fast degradation, post-implantation reactions, imbalanced osteogenicity (Bellucci et al., 2014;Bian et al., 2014;Goel et al., 2012;Gu et al., 2013;Hoppe et al., 2011;Sarker et al., 2015;Sriranganathan et al., 2016;Dorozhkin, 2010;Lei et al., 2017;Mondal et al., 2018;Yang et al., 2018;Ke et al., 2017;Lee et al., 2017;Taktak et al., 2018;Yang et al., 2015a;Liu et al., 2016;Shokrollahi et al., 2017;Shuai et al., 2015) Natural polymer (Mimics to ECM, biocompatibility, Enzymatic biodegradability, Structural Complexity, Poor mechanical strength) Collagen/Gelatin (Denaturalized collagen)Organic bone constituent, conjugated with various organic, inorganic, polymeric compoundComplex structure, sterility, immunogenicity, tedious handling (Elango et al., 2016;Lee et al., 2018b;Wang et al., 2016c;Mazaki et al., 2014;Shi et al., 2017;Wang et al., 2018;Xia et al., 2012) Chitosan Positively charged polysaccharide, resistant to bacteria Provide support for cellular adhesion, osteogenesis, non-toxic, non-allergenicity, and osteoconductivePoor mechanical strength (Soundarya et al., 2018) Hyaluronic acid (HA) negatively charged glycosaminoglycan (GAG)Easy functionalization, viscoelastic Rapid degradation (Cui et al., 2015;Dai Prè et al., 2016;Gokila et al., 2018;Manferdini et al., 2010;Patterson et al., ...
Chapter
Bone is dynamic tissues have structural and functional complexity with varying mechanical strength as of skeletal, craniofacial maxillary position. Despite surgery, allograft, advanced therapy, treatment of critical defects, deformities and functional restoration of bone are still challenging. BTE provides the hope, which could resolve the surgical challenges by developing the artificial functionalized bone. Use of biodegradable polymers in BTE provides variable required mechanical properties, porosity, and surface microenvironment for cellular adhesion, osteoblast proliferation and differentiation. Non-antigenic, immunomodulatory, vascularization, cytocompatibility, adjustable degradation kinetics, hydrolytic/enzymatic degradation and release of biocompatible metabolites are the main characteristics that enable biodegradable polymers for making 3D-scaffold for BTE. In the above line, this article illustrates the different biodegradable polymers that useful for the bone microenvironment and for the repair bone tissues.
... 14 Many studies have reported that primary cultured BMSCs isolated from small animals such as mice, rats, or rabbits have a good biocompatibility with biomaterials. [15][16][17] BMSCs therapy combined with different biomaterials may improve bone regeneration in dental implantation. 18,19 Promoting osseointegration of BMSCs on the surface of zirconia ceramics was the focus of this study. ...
Article
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Zirconia is considered the most promising alternative material to titanium implants. However, zirconia is a biologically inert material and its surface modification is essential to obtain efficient osseointegration. Plasma immersion ion implantation (PIII) is a controllable and flexible approach that constructs functional groups on the surface of biomaterials and enhances osteogenic ability of host osteoclast cells. Zirconia disks were randomly divided into 4 groups (n = 50/group): (1) Blank, (2) C60N0, (3) C60N6, and (4) C60N18. Carbon and nitrogen plasma immersion ion implantation on zirconia (C and N2-PIII) surface modification was completed with the corresponding parameters. When zirconia was modified by carbon and nitrogen plasma implantation, a new chemical structure was formed on the material surface while the surface roughness of the material remained unaltered. The nitrogen-containing functional groups with high potential were introduced but the bulk crystal structure of zirconia was not changed, indicating that the stability of zirconia was not affected. In vitro data showed that zirconia with high surface potential promoted adhesion, proliferation, and osteogenic differentiation of BMSCs. C60N6 was found to be superior to the other groups. Our results demonstrate that a zirconia surface modified by C and N2-PIII can introduce desirable nitrogen functional groups and create a suitable extracellular environment to promote BMSCs biological activity. Taken together, these results suggest that C and N2-PIII modified zirconia is a promising material for use in the field of medical implantation.
... This results from the fact that different starting conditions apply to MSCs from different tissues. In plastic surgery, large amounts of fat tissue are usually produced, from which high numbers of AD-MSCs can be isolated in the initial step, which is why in vitro studies can usually be performed by the participating laboratory in passage 2 to 5 [26,27,60]. The situation is somewhat less favorable with BM-MSCs since only limited sample quantities can be generated during surgical procedures or iliac crest punctures. ...
... In the case of DP-MSCs, data regarding the influence of extended cultivation in vitro suggest an increasing predetermination for certain differentiation lineages and a reduced osteogenic capacity for only very high passages [61,62]. Results of studies with AD-MSCs did not indicate passage-dependent differentiation capacities [26,27,60]. ...
Article
Background aims Mesenchymal stroma/stem-like cells (MSCs) are a popular cell source and hold huge therapeutic promise for a broad range of possible clinical applications. However, to harness their full potential, current limitations in harvesting, expansion and characterization have to be overcome. These limitations are related to the heterogeneity of MSCs in general as well as to inconsistent experimental protocols. Here we aim to compare in vitro methods to facilitate comparison of MSCs generated from various tissues. Methods MSCs from 3 different tissues (bone marrow, dental pulp, adipose tissue), exemplified by cells from 3 randomly chosen donors per tissue, were systematically compared with respect to their in vitro properties after propagation in specific in-house standard media, as established in the individual laboratories, or in the same commercially available medium. Results Large differences were documented with respect to the expression of cell surface antigens, population doubling times, basal expression levels of 5 selected genes and osteogenic differentiation. The commercial medium reduced differences in these parameters with respect to individual human donors within tissue and between tissues. The extent, size and tetraspanin composition of extracellular vesicles were also affected. Conclusions The results clearly demonstrate the extreme heterogeneity of MSCs, which confirms the problem of reproducibility of results, even when harmonizing experimental conditions, and questions the significance of common parameters for MSCs from different tissues in vitro.
... When NiTi shifts between the austenite and martensite forms, nanoparticles of this material also experience a change in electrical and thermal conductivity, which may allow NiTi to act as a chemical sensor in the form of a smart nanofluid [1,7]. In terms of medical applications, the shape memory and flexibility of NiTi metal has been exploited to create a less invasive heart stent [6]. ...
... In terms of medical applications, the shape memory and flexibility of NiTi metal has been exploited to create a less invasive heart stent [6]. NiTi nanoparticles have been shown to exhibit bioactive properties, leading to the belief that NiTi nanoparticles could be used to assist in cellular adhesion to biomaterials, such as bone implants and prosthetics, and have also been tested to target cancer cells for apoptosis [7][8][9]. Furthermore, Ni-based electrodes have received increased attention because of their excellent electrochemical properties and applications in rechargeable Ni-based alkaline batteries [10]. However, most of these alloy electrodes are difficult to operate due to the oxidation of the electrode and complications controlling the size of the particles during fabrication. ...
Article
Nitinol (NiTi) nanoparticles are a valuable metal alloy due to many unique properties that allow for medical applications. NiTi nanoparticles have the potential to form nanofluids, which can advance the thermal conductivity of fluids by controlling the surface functionalization through chemical attachment of organic acids to the surface to form self-assembled alkylphosphonate films. In this study, phosphonic functional head groups such as 16-phosphonohexadecanoic acid, octadecylphosphonic acid, and 12-aminododecylphosphonic acid were used to form an ordered and strongly chemically bounded film on the NiTi nanopowder. The surface of the NiTi nanoparticles was modified in order to tailor the chemical and physical properties to the desired application. The modified NiTi nanoparticles were characterized using infrared spectroscopy, powder X-ray diffraction, X-ray photoelectron spectroscopy, and ³¹P solid-state nuclear magnetic resonance. The interfacial bonding was identified by spectroscopic data suggesting the phosphonic head group adsorbs in a mixed bidentate/monodentate binding motif on the NiTi nanoparticles. Dynamic light scattering and scanning electron microscopy-energy dispersive X-ray spectroscopy revealed the particle sizes. Differential scanning calorimetry was used to examine the phase transitions. Zeta potential determination as a function of pH was examined to investigate the surface properties of charged nanoparticles. The influence of environmental stability of the surface modifications was also assessed.
... In the end, the cellular response to materials depends on the specific cell types, materials processing, and testing conditions [10,32,60]. Furthermore, surface roughness, topography, and chemistry are crucial factors for cell adhesion, proliferation, and differentiation [3,8,14,[61][62][63][64][65]. In our present in vitro study, the Ti6Al4V and NiTi alloys also differed strongly in roughness values. ...
Article
Full-text available
The biomaterials used to maintain or replace functions in the human body consist mainly of metals, ceramics or polymers. In orthopedic surgery, metallic materials, especially titanium and its alloys, are the most common, due to their excellent mechanical properties, corrosion resistance, and biocompatibility. Aside from the established Ti6Al4V alloy, shape memory materials such as nickel-titanium (NiTi) have risen in importance, but are also discussed because of the adverse effects of nickel ions. These might be reduced by specific surface modifications. In the present in vitro study, the osteoblastic cell line MG-63 as well as primary human osteoblasts, fibroblasts, and macrophages were cultured on titanium alloys (forged Ti6Al4V, additive manufactured Ti6Al4V, NiTi, and Diamond-Like-Carbon (DLC)-coated NiTi) to verify their specific biocompatibility and inflammatory potential. Additive manufactured Ti6Al4V and NiTi revealed the highest levels of metabolic cell activity. DLC-coated NiTi appeared as a suitable surface for cell growth, showing the highest collagen production. None of the implant materials caused a strong inflammatory response. In general, no distinct cell-specific response could be observed for the materials and surface coating used. In summary, all tested titanium alloys seem to be biologically appropriate for application in orthopedic surgery.
... Similar to HTMCs, decreased proliferation has been observed in endothelial cells cultured on nitinol compared with glass control. 26,38 Furthermore, another study by Shih et al. found that nitinol corrosion products inhibit rat aortic smooth muscle cell proliferation. 39 The low proliferation rate of HTMCs on nitinol may be due to a similar process. ...
Article
Background: Microinvasive glaucoma surgery (MIGS) is a relatively new addition to the glaucoma treatment paradigm. Small metallic stents are inserted into the trabecular meshwork in order to increase aqueous humour drainage. MIGS procedures are rapidly being adopted due to a more favourable side effect profile when compared to traditional surgery. Remarkably, this rapid rate of utilization has occurred without any published studies on the effect of metal alloys used in these stents on human trabecular meshwork cells (HTMCs). Therefore, this study aimed to determine the effect of candidate metal alloys for micro-invasive glaucoma surgery on HTMC morphology, viability, and function. Methods: HTMCs were cultured on the surfaces of titanium (polished and sandblasted), a titanium-nickel (nitinol) alloy, and glass (as control substratum). Fluorescence imaging was used to assess cell morphology and spreading. A lactate dehydrogenase cytotoxicity assay, cell death detection ELISA, MTT cell viability assay, BrdU cell proliferation assay, and fibronectin ELISA were also conducted. Results: Cells cultured on sandblasted titanium exhibited significantly greater spreading than cells cultured on other substrata. In comparison, HTMCs cultured on nitinol displayed poor spreading. Significantly more cell death, by both necrosis and apoptosis, occurred on nitinol than on titanium and glass. Also, cell viability and proliferation were suppressed on nitinol compared to titanium or glass. Finally, HTMCs on both titanium and nitinol produced greater amounts of fibronectin than cells grown on glass. Conclusions: Substratum topography and metal alloy composition were found to impact morphology, viability, and function of primary HTMC cultures.