Enhancement of plasma protein adsorption and osteogenesis of hMSCs by functionalized siloxane coatings for titanium implants

A series of sol–gel derived silicon based coatings were developed to improve the osseointegration of commer- cial titanium dental implants. The osseointegration starts with a positive interaction between the implant surface and surrounding tissues, which is facilitated by the adsorption of plasma proteins onto the biomaterial surface immediately after implantation. It is likely that the enhancement of protein adsorption to titanium implants leads to a better implant/tis- sue integration. In addition, silica based biomaterials have been shown to promote osteoblast differentiation. To improve the protein adsorption and the osteogenesis, meth- yltrimethoxysilane (MTMOS), tetraethoxysilane (TEOS), 3- glycidoxypropyltrimethoxysilane (GPTMS), and gelatin were selected to coat titanium surfaces. Compared with non- coated titanium, the functionalized coatings enhanced the adsorption of adhesive proteins such as fibronectin and colla- gen. The Si release was successfully modulated by the con- trol of the chemical composition of the coating, showing a higher dissolution rate with the gelatin and GPTMS incorpo- ration. While the roughness of commercial implants seemed to promote the adhesion of mesenchymal stem cells (MSC), the osteogenic differentiation was greater on surfaces with Si-coatings. In this study, an improved osteogenic surface has been achieved by using the siloxane-gelatin coatings and such coatings can be used in dental implants to promote osseointegration

Design of nanostructured siloxane-gelatin coatings: Immobilization strategies and dissolution properties

Owing to the outstanding service life of metallic prostheses, a substantial effort has been put into their surface modification to improve biocompatibility and reduce metallic ion diffusion. To satisfy these requirements, the coating materials obtained using the sol-gel method, with its wide range of tuning properties, have been extensively explored. The well-known biocompatibility of these materials makes them good candidates for different biomedical applications. We designed a series of siloxane-gelatin hybrids to be used as coatings for metallic implants or in controlled delivery systems. Two different matrixes were designed based on methyltrimethoxysilane (MTMOS), tetraethoxysilane (TEOS) and 3-glycidoxypropyltrimethoxysilane (GPTMS) alkoxysilane precursors. In one hybrid coating gelatin was physically entrapped and in the other it was linked to the siloxane network by covalent bonds. Synthesis parameters were established by studying the sol-gel reaction using 29Si nuclear magnetic resonance (29Si NMR), which also allowed quantification of the network connectivity. Dissolution and degradation studies showed the effectiveness of GPTMS as a covalent coupling agent between the silica and gelatin phases; it increased the stability of the coatings in aqueous media. The aim of this study was to design a set of hybrid materials with highly tailorable properties, suitable for their potential biomedical application

Synthesis and characterization of silica-chitosan hybrid materials as antibacterial coatings for titanium implants

To avoid dental implant-related infections and to promote the osseointegration of titanium implants, the application of silicon and chitosan containing coatings is proposed. Silicon is a well-known osteogenic element and chitosan was selected to confer the antibacterial properties. The synthesis of hybrid silica-chitosan coatings using the sol-gel process is presented and the characterization using 29Si-NMR to verify the correct formation of the network is discussed. The 13C NMR spectroscopy was used to confirm the covalent union between chitosan and the silicon network. Hydrolytic degradation and silicon release studies showed the effective silicon release from the hybrids and, hence, the possibility to promote bone formation. The introduction of different amounts of chitosan and tetraethyl orthosilicate (TEOS) modulated the Si release. The analysis of cell cultures in vitro demonstrated that the hybrid coatings were not cytotoxic and promoted cell proliferation on their surfaces. The coatings containing 5%–10% chitosan had substantial antibacterial properties

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

This is the peer reviewed version of the following article: Nanomedicine: Nanotechnology, Biology and Medicine (2016): 59-65, which has been published in final form at http://dx.doi.org/10.1016/j.nano.2015.12.3676α-Methylprednisolone-loaded surfactant-free nanoparticles have been developed to palliate cisplatin ototoxicity. Nanoparticles were based on two different amphiphilic pseudo-block copolymers obtained by free radical polymerization and based on N-vinyl pyrrolidone and a methacrylic derivative of α-tocopheryl succinate or α-tocopherol. Copolymers formed spherical nanoparticles by nanoprecipitation in aqueous media that were able to encapsulate 6α-methylprednisolone in their inner core. The obtained nanovehicles were tested in vitro using HEI-OC1 cells and in vivo in a murine model. Unloaded nanoparticles were not able to significantly reduce the cisplatin ototoxicity. Loaded nanoparticles reduced cisplatin-ototoxicity in vitro being more active those based on the methacrylic derivative of vitamin E, due to their higher encapsulation efficiency. This formulation was able to protect hair cells in the base of the cochlea, having a positive effect in the highest frequencies tested in a murine model. A good correlation between the in vitro and the in vivo experiments was foun

Influence of zinc molybdenum phosphate pigment on coatings performance studied by electrochemical methods

The effect of the addition of the zinc molybdenum phosphate pigment, on the corrosion resistance properties of powder coating on steel, has been investigated by means of different electrochemical methods: electrochemical impedance spectroscopy (EIS) and the accelerated cyclic electrochemical technique (ACET). Anticorrosive properties obtained from both techniques showed similar results. Powder coatings incorporating this pigment have shown better performance which is attributed to both barrier properties enhancement and inhibition action of the pigment. This behavior can be correlated to the results obtained in the pigment extract study (polarization test and EIS). Finally, salt fog spray test was performed to confirm the electrochemical tests results.The authors would like to acknowledge Nubiola S.A. for supplying the raw materials, as well as Raquel Oliver and José Ortega for their help in the development of this project

Control of the degradation of silica sol-gel hybrid coatings for metal implants prepared by the triple combination of alkoxysilanes

Hybrid materials obtained by sol-gel process are able to degrade and release Si compounds that are useful in regenerative medicine due to their osteoinductive properties. The present work studies the behavior of new organic-inorganic sol-gel coatings based on triple mixtures of alkoxysilanes in different molar ratios. The precursors employed are methyl-trimethoxysilane (MTMOS), 3-glycidoxypropyl-trimethoxysilane (GPTMS) and tetraethyl-orthosilicate (TEOS). After optimization of the synthesis conditions, the coatings were characterized using 29Si nuclear magnetic resonance (29Si-MNR), Fourier transform infrared spectrometry (FT-IR), contact angle measurements, hydrolytic degradation assays, electrochemical impedance spectroscopy (EIS) and mechanical profilometry. The degradation and EIS results show that by controlling the amount of TEOS precursor in the coating it is possible to tune its degradation by hydrolysis, while keeping properties such as wettability at their optimum values for biomaterials application. The corrosion properties of the new coatings were also evaluated when applied to stainless steel substrate. The coatings showed an improvement of the anticorrosive properties of the steel which is important to protect the metal implants at the early stages of the regeneration process.The financial support of MAT2014-51918-C2-2-R, P11B2014-19 and Plan de Promoción de la Investigación from the Universitat Jaume I (Predoc/2014/25) is gratefully acknowledged. J. García-Cañadas acknowledge financial support from Ramón y Cajal programme (RYC-2013-13970). The experimental support of Raquel Oliver Valls and José Ortega Herreros is also acknowledged

Development and characterisation of strontium-doped sol-gel coatings to optimise the initial bone regeneration processes

Strontium plays an important role in bone regeneration; it promotes the differentiation and maturation of osteoblasts and inhibits the activity of osteoclasts. Our principal objective in this study was to formulate new organic-inorganic hybrid sol-gel coatings applied to titanium discs. These coatings were functionalised with different amounts of SrCl2 and examined using in vitro tests and proteomics. The chemical and morphological characteristics of obtained coatings were scrutinised. The in vitro evaluation using the MC3T3-E1 osteoblasts and RAW264.7 macrophages showed the osteogenic and anti-inflammatory effects of strontium doping. The proteomic assay identified 111 different proteins adhering to the coatings. Six of these proteins reduced their adhesion affinity as a result of Sr-doping, whereas 40 showed increased affinity. Moreover, the proteomic analysis revealed osteogenic and anti-inflammatory properties of these biomaterials. The analysis also showed increased adhesion of proteins related to the coagulation system. We can conclude that proteomic methods are invaluable in developing new biomaterials and represent an important tool for predicting the biocompatibility of dental implants

Proteomic analysis of silica hybrid sol-gel coatings: a potential tool for predicting the biocompatibility of implants in vivo

The interactions of implanted biomaterials with the host organism determine the success or failure of an implantation. Normally, their biocompatibility is assessed using in vitro tests. Unfortunately, in vitro and in vivo results are not always concordant; new, effective methods of biomaterial characterisation are urgently needed to predict the in vivo outcome. As the first layer of proteins adsorbed onto the biomaterial surfaces might condition the host response, mass spectrometry analysis was performed to characterise these proteins. Four distinct hybrid sol-gel biomaterials were tested. The in vitro results were similar for all the materials examined here. However, in vivo, the materials behaved differently. Six of the 171 adsorbed proteins were significantly more abundant on the materials with weak biocompatibility; these proteins are associated with the complement pathway. Thus, protein analysis might be a suitable tool to predict the in vivo outcomes of implantations using newly formulated biomaterials

Proteomic Analysis of Mesenchymal Stem Cells and Monocyte Co-Cultures Exposed to a Bioactive Silica-Based Sol–Gel Coating

New methodologies capable of extensively analyzing the cell-material interactions are necessary to improve current in vitro characterization methods, and proteomics is a viable alternative. Also, many studies are focused on monocultures, even though co-cultures model better the natural tissue. For instance, human mesenchymal stem cells (MSCs) modulate immune responses and promote bone repair through interaction with other cell types. Here, label-free liquid chromatography tandem mass spectroscopy proteomic methods were applied for the first time to characterize HUCPV (MSC) and CD14+ monocytes co-cultures exposed to a bioactive sol–gel coating (MT). PANTHER, DAVID, and STRING were employed for data integration. Fluorescence microscopy, enzyme-linked immunosorbent assay, and ALP activity were measured for further characterization. Regarding the HUCPV response, MT mainly affected cell adhesion by decreasing integrins, RHOC, and CAD13 expression. In contrast, MT augmented CD14+ cell areas and integrins, Rho family GTPases, actins, myosins, and 14-3-3 expression. Also, anti-inflammatory (APOE, LEG9, LEG3, and LEG1) and antioxidant (peroxiredoxins, GSTO1, GPX1, GSHR, CATA, and SODM) proteins were overexpressed. On co-cultures, collagens (CO5A1, CO3A1, CO6A1, CO6A2, CO1A2, CO1A1, and CO6A3), cell adhesion, and pro-inflammatory proteins were downregulated. Thus, cell adhesion appears to be mainly regulated by the material, while inflammation is impacted by both cellular cross-talk and the material. Altogether, we conclude that applied proteomic approaches show its potential in biomaterial characterization, even in complex systems.This work was supported by MINECO [MAT2017-86043-R; RTC-2017-6147-1], Generalitat Valenciana [GRISOLIAP/2018/091, BEFPI/2021/043, PROMETEO/2020/069], Universitat Jaume I [UJI-B2017-37], and the University of the Basque Country [GIU18/189]. Andreia Cerqueira was supported by the Margarita Salas postdoctoral contract MGS/2022/10 (UP2022-024) financed by the European Union-NextGenerationEU. The University Medical Centre Hamburg-Eppendorf (Hamburg, Germany) and the Clinics for Gynecology AGAPLESION BETHESDA Hospital provided the blood and tissue for cell isolation. The authors would like to thank Raquel Oliver, Jose Ortega, Iraide Escobés, and Anke Borkam-Schuster for their valuable technical assistance and Antonio Coso (GMI-Ilerimplant) for producing the titanium discs