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In order to identify new bioactive glasses (BGs) with optimal antioxidant properties, we carried out an evaluation of a series of cerium-doped BGs [Ce-BGs─H, K, and mesoporous bioactive glasses (MBGs)] loaded with different biomolecules, namely, gallic acid, polyphenols (POLY), and anthocyanins. Quantification of loading at variable times highlighted POLY on MBGs as the system with the highest loading. The ability to dismutate hydrogen peroxide (catalase-like activity) of the BGs evaluated is strongly correlated with cerium doping, while it is marginally decreased compared to the parent BG upon loading with biomolecules. Conversely, unloaded Ce-BGs show only a marginal ability to dismutate the superoxide anion (SOD)-like activity, while upon loading with biomolecules, POLY in particular, the SOD-like activity is greatly enhanced for these materials. Doping with cerium and loading with biomolecules give complementary antioxidant properties to the BGs investigated; combined with the persistent bioactivity, this makes these materials prime candidates for upcoming studies on biological systems.

The so-called BGMS10, a bioactive glass containing 10 mol.% SrO and 10 mol.% MgO, displays a low inclination to crystallize, as confirmed by its high activation energy (538.9 kJ/mol). Such peculiar aspect and the beneficial use of SPS allow for the obtainment of 99.7 % dense and fully amorphous products at 750 °C. The incipient crystallization in the glass is observed when temperature is increased to 850 °C, while 95 wt. % crystallized ceramics are produced at 950 °C. Main crystalline phases are α- and β-CaSiO3, with grain size of 89 and 97 nm, respectively. Glass crystallization is accompanied by Young’s modulus increase from 90.92 to 98.38 GPa. On the other hand, partially crystallized samples (850 °C) exhibit higher Vickers hardness (718.8) compared to fully crystallized ones (619.8), which show lower density (98.6%). In-vitro tests in SBF indicate that the silica-gel film preceding apatite nucleation is mostly formed on the amorphous substrate region.

Successful tissue regeneration requires a scaffold with tailorable biodegradability, tissue-like mechanical properties, structural similarity to extracellular matrix (ECM), relevant bioactivity, and cytocompatibility. In recent years, injectable hydrogels have spurred increasing attention in translational medicine as a result of their tunable physicochemical properties in response to the surrounding environment. Furthermore, they have the potential to be implanted via minimally invasive procedures while enabling deep penetration, which is considered a feasible alternative to traditional open surgical procedures. However, polymeric hydrogels may lack sufficient stability and bioactivity in physiological environments. Composite hydrogels containing bioactive glass (BG) particulates, synergistically combining the advantages of their constituents, have emerged as multifunctional biomaterials with tailored mechanical properties and biological functionalities. This review paper highlights the recent advances in injectable composite hydrogel systems based on biodegradable polymers and BGs. The influence of BG particle geometry, composition, and concentration on gel formation, rheological and mechanical behavior as well as hydration and biodegradation of injectable hydrogels have been discussed. The applications of these composite hydrogels in tissue engineering are additionally described, with particular attention to bone and skin. Finally, the prospects and current challenges in the development of desirable injectable bioactive hydrogels for tissue regeneration are discussed to outline a roadmap for future research. Statement of significance Developing a biomaterial that can be readily available for surgery, implantable via minimally invasive procedures, and be able to effectively stimulate tissue regeneration is one of the grand challenges in modern biomedicine. This review summarizes the state-of-the-art of injectable bioactive glass-polymer composite hydrogels to address several challenges in bone and soft tissue repair. The current limitations and the latest evolutions of these composite biomaterials are critically examined, and the roles of design parameters, such as composition, concentration, and size of the bioactive phase, and polymer-glass interactions on the rheological, mechanical, biological, and overall functional performance of hydrogels are detailed. Existing results and new horizons are discussed to provide a state-of-the-art review that may be useful for both experienced and early-stage researchers in the biomaterials community.

Bioactive glasses (BGs) are promising for bone tissue regeneration. BG composition can be tailored, according to the application of interest, and/or functionalized with organic molecules/biomolecules to improve their per- formances. However, despite the wide knowledge concerning BGs, their interaction with proteins, fundamental for controlling the fate of the implant, has not been deeply investigated yet. Controlling or predicting protein adsorption requires a full understanding of the materials surface physico-chemical properties. In this work, four different BGs (S53P4, B25, SCNB, PhGlass) were surface-modified by four different treatments: 72 h-soaking in TRIS, 72 h soaking in simulated body fluid, APTES grafting and quaternized APTES grafting. The surfaces were then characterized both untreated and after each treatment by contact angle, zeta potential analysis, X-ray photoelectron spectroscopy, Fourier Transform InfraRed–Attenuated Total Reflectance spectroscopy and Scan- ning Electron Microscopy and Energy Dispersive Spectroscopy. Inductively Coupled Plasma – Optical Emission Spectrometry was then performed to investigate the ion leaching. The aim of this study (Part I) is the physico- chemical characterization of BGs as a function of the implemented treatments, aiming to better understand how the superficial properties are successively affecting protein adsorption. Protein adsorption on untreated and treated BGs will be discussed in a following manuscript (Part II).&nbsp

Electrophoretic deposition (EPD) is a powerful technique to assemble metals, polymer, ceramics, and composite materials into 2D, 3D, and intricately shaped implants. Polymers, proteins, and peptides can be deposited via EPD at room temperature without affecting their chemical structures. Furthermore, EPD is being used to deposit multifunctional coatings (i.e., bioactive, antibacterial, and biocompatible coatings). Recently, EPD was used to architect multi-structured coatings to improve mechanical and biological properties along with the controlled release of drugs/metallic ions. The key characteristics of EPD coatings in terms of inorganic bioactivity and their angiogenic potential coupled with antibacterial properties are the key elements enabling advanced applications of EPD in orthopedic applications. In the emerging field of EPD coatings for hard tissue and soft tissue engineering, an overview of such applications will be presented. The progress in the development of EPD-based polymeric or composite coatings, including their application in orthopedic and targeted drug delivery approaches, will be discussed, with a focus on the effect of different biologically active ions/drugs released from EPD deposits. The literature under discussion involves EPD coatings consisting of chitosan (Chi), zein, polyetheretherketone (PEEK), and their composites. Moreover, in vitro and in vivo investigations of EPD coatings will be discussed in relation to the current main challenge of orthopedic implants, namely that the biomaterial must provide good bone-binding ability and mechanical compatibility.

This paper shows the determination of the most energy efficient composition for molding of bioglasses in the SiO2 -Na2O-CaO-P2O5 system. Ten compositions were formulated in the range where the glass has a bioactivity index greater than 8 and the curves of viscosity as a function of temperature were drawn using the Vogel-Fulcher-Tammann (VFT) equation. Analyzing the curves, the composition 43SiO2 -30CaO-21Na2O-6P2O5 has the lowest viscosity over the entire working temperature range, requiring less heat to be molded and consequently consuming less energy in the ovens.

In this study, a promising relationship between antibacterial zone and radiation attenuation properties was investigated in Ag2O doped bioactive glasses with a chemical composition of xAg2O–20Li2O–25TeO2-(55-x)B2O3 (where x = 0, 0.5, 1.0, 1.5, and 2.0 mol%). For this aim, a wide-ranging radiation attenuation characterization procedure was performed on Ag2O substituted bioactive glasses. The general-purpose Monte Carlo code MCNPX (v.2.7.0) was used to model bioactive glasses. The mass attenuation coefficients were calculated using a gamma-ray transmission setup. The coefficients obtained were used to determine other important attenuation properties. Finally, for particular behaviors, exposure (EBF) and energy absorption (EABF) build-up factors were calculated for specific attitudes of Ag2O substitutions in bioactive glasses during the interaction process. The results showed that there is direct relationship between Ag2O substitution amount and radiation attenuation properties. In addition to its well-behaviors on inhibition zone against bacterial occurrences, it can be concluded that increasing Ag2O would increase the gamma-ray attenuation properties of studied bioactive glass system. © 2021 The Authors The authors thank for the scholar and research grant under Universiti Putra Malaysia , Taif University Researchers Supporting Project number (TURSP-2020/12), Taif University , Saudi Arabia and Deanship of Scientific Research at King Khalid University for financial support through General Research Project under grant number ( G.R.P/81/42 ).

Zn-containing dense monodispersed bioactive glass nanoparticles (Zn-BAGNPs) have been developed to deliver therapeutic inorganic trace elements, including Si, Ca, Sr, and Zn, to the cells through the degradation process, as delivery carriers for stimulating bone regeneration because of their capacity to induce osteogenic differentiation. The sol–gel-derived dense silica nanoparticles (SiO2-NPs) were first synthesized using the modified Stöber method, prior to incorporating therapeutic cations through the heat treatment process. The successfully synthesized monodispersed Zn-BAGNPs (diameter of 130 ± 20 nm) were homogeneous in size with spherical morphology. Ca, Sr and Zn were incorporated through the two-step post-functionalization process, with the nominal ZnO ratio between 0 and 2 (0, 0.5, 1.0, 1.5 and 2.0). Zn-BAGNPs have the capacity for continuous degradation and simultaneous ion release in SBF and PBS solutions due to their amorphous structure. Zn-BAGNPs have no in vitro cytotoxicity on the murine pre-osteoblast cell (MC3T3-E1) and periodontal ligament stem cells (PDLSCs), up to a concentration of 250 µg/mL. Zn-BAGNPs also stimulated osteogenic differentiation on PDLSCs treated with particles, after 2 and 3 weeks in culture. Zn-BAGNPs were not toxic to the cells and have the potential to stimulate osteogenic differentiation on PDLSCs. Therefore, Zn-BAGNPs are potential vehicles for therapeutic cation delivery for applications in bone and dental regenerations.

The use of organic–inorganic 3D printed composites with enhanced properties in biomedical applications continues to increase. The present study focuses on the development of 3D printed alginate-based composites incorporating inorganic fillers with different shapes (angular and round), for bone regeneration. Reactive fillers (bioactive glass 13–93 and hydroxyapatite) and non-reactive fillers (inert soda–lime glass) were investigated. Rheological studies and the characterization of various extrusion-based parameters, including material throughput, printability, shape fidelity and filament fusion, were carried out to identify the parameters dominating the printing process. It was shown that the effective surface area of the filler particle has the highest impact on the printing behavior, while the filler reactivity presents a side aspect. Composites with angular particle morphologies showed the same high resolution during the printing process, almost independent from their reactivity, while composites with comparable amounts of round filler particles lacked stackability after printing. Further, it could be shown that a higher effective surface area of the particles can circumvent the need for a higher filler content for obtaining convincing printing results. In addition, it was proven that, by changing the particle shape, the critical filler content for the obtained adequate printability can be altered. Preliminary in vitro biocompatibility investigations were carried out with the bioactive glass containing ink. The 3D printed ink, forming an interconnected porous scaffold, was analyzed regarding its biocompatibility in direct or indirect contact with the pre-osteoblast cell line MC3T3-E1. Both kinds of cell tests showed increased viability and a high rate of proliferation, with complete coverage of the 3D scaffolds’ surface already after 7 d post cell-seeding.

Objectives Dentin hypersensitivity (DH) is mainly due to the loss and replenishment of minerals from tooth structure, where the lost minerals can be rehabilitated with a biomimetic approach. The objectives were to determine the relative dentin abrasivity (RDA) of experimental (EXT) dentifrices and to determine the efficacy to occlude dentinal tubules. Materials and Methods Experimental dentifrices contained nano-fluoridated bioactive glass (n-FBG: 1.5 wt.% [EXT-A], 2.5 wt.% [EXT-B], and 3.5 wt.% [EXT-C]), nano-zinc oxide (n-ZnO), and thymoquinone as active agents. Bovine dentin blocks were subjected to brushing treatments as per groups, that is, distilled water; commercial dentifrice (control, CT); EXT toothpastes; and EXT-D without active agents. Samples were tested for three-dimensional (3D) abrasion analysis according to ISO-11609:2010 (International Organization for Standardization [ISO]). The roughness average (Ra), RDA, surface topography, and elemental compositions were investigated. Statistical Analysis One-way analysis of variance (ANOVA) with post-hoc Tukey’s and Tamhane’s test was performed for characterizations using Statistical Package for the Social Sciences (SPSS) version 21. The result was considered significant with p-value ≤ 0.05. Results Comparisons of Ra differed significantly between all groups with p < 0.05 except CT and EXT-A. The RDA values of EXT-A, EXT-B, and EXT-C were calculated as 74.04, 84.26, and 116.24, respectively, which were well within the acceptable limit set by international standards. All n-FBG containing dentifrices demonstrated uniform occlusion of dentinal tubules; however, highly concentrated EXT dentifrices showed more occlusion. Conclusions Acceptable range of RDA and superior occlusion of tubules by novel dentifrices suggest that it may be recommended for treating DH.

The present review deals with bioactive glasses (BGs), a class of biomaterials renowned for their osteoinductive and osteoconductive capabilities, and thus widely used in tissue engineering, i.e., for the repair and replacement of damaged or missing bone. In particular, the paper deals with applications in periodontal regeneration, with a special focus on in vitro, in vivo and clinical studies. The study reviewed eligible publications, identified on the basis of inclusion/exclusion criteria, over a ranged time of fifteen years (from 1 January 2006 to 31 March 2021). While there are many papers dealing with in vitro tests, only a few have reported in vivo (in animal) research, or even clinical trials. Regardless, BGs seem to be an adequate choice as grafts in periodontal regeneration.

Agradecimentos: The authors acknowledge the facility support from the Universidade Federal do ABC, Central Experimental Multiusuário, Politecnico di Torino, Universidade de São Paulo, Hospital Israelita Albert Einstein and Jena University. The authors also thank MSc. Marcela Tercini and BSc. João Francisco Almeida by the technical support in the FE-SEM analysis. We also acknowledge E.S.R. Somessari from Centro de Tecnologia das Radiações at Instituto de Pesquisas Energéticas e Nucleares (SETRS/CTR-IPEN) for technical support on sample sterilization. Furthermore, the authors appreciate the financial support from FAPESP (#2016/16512-9, #2011/19924-2 and 2020/00329-6), FINEP, CNPq (#130637/2016-5), and CAPES (code 002) Abstract: Magnetic bioactive glass-ceramics are biomaterials applied for magnetic hyperthermia in bone cancer treatment, thereby treating the bone tumor besides regenerating the damaged bone. However, combining high bioactivity and high saturation magnetization remains a challenge since the thermal treatment step employed to grow magnetic phases is also related to loss of bioactivity. Here, we propose a new nanocomposite made of superparamagnetic iron oxide nanoparticles (SPIONs) dispersed in a sol-gel-derived bioactive glass matrix, which does not need any thermal treatment for crystallization of magnetic phases. The scanning and transmission electron microscopies, X-ray diffraction, and dynamic light scattering results confirm that the SPIONs are actually embedded in a nanosized glass matrix, thus forming a nanocomposite. Magnetic and calorimetric characterizations evidence their proper behavior for hyperthermia applications, besides evidencing inter-magnetic nanoparticle interactions within the nanocomposite. Bioactivity and in vitro characterizations show that such nanocomposites exhibit apatite-forming properties similar to the highly bioactive parent glass, besides being osteoinductive. This methodology is a new alternative to produce magnetic bioactive materials to which the magnetic properties only rely on the quality of the SPIONs used in the synthesis. Thereby, these nanocomposites can be recognized as a new class of bioactive materials for applications in bone cancer treatment by hyperthermia FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP FINANCIADORA DE ESTUDOS E PROJETOS - FINEP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES Fechado

The silicate-based bioactive glass S53P4 is clinically used in bone regenerative applications in granule form. However, utilization of the glass in scaffold form has been limited by the high tendency of the glass to crystallize during sintering. Here, careful optimization of sintering parameters enabled the manufacture of porous amorphous S53P4 scaffolds with a strength high enough for surgical procedures in bone applications (5 MPa). Sintering was conducted in a laboratory furnace for times ranging from 25 to 300 min at 630 degrees C, i.e., narrowly below the commencement of the crystallization. The phase composition of the scaffolds was verified with XRD, and the ion release was tested in vitro and compared with granules in continuous flow of Tris buffer and simulated body fluid (SBF). The amorphous, porous S53P4 scaffolds present the possibility of using the glass composition in a wider range of applications.

The in-vitro behaviour of three series of dense materials with different crystallization degree and phases produced by Spark Plasma Sintering (SPS) from CaO-rich bioglass powders is investigated by soaking them up to 14 days in Simulated Body Fluid (SBF). The completely amorphous materials produced after 2 min at 730 °C display the more pronounced substrate-solution interaction. This is highly beneficial for the rapid generation (

Here, molecular dynamics simulations have been carried out on phosphate glasses to clarify the previously debated influence of fluoride on the bioactivity of these glasses. We developed a computationally advanced inter-atomic force field including polarisation effects of the fluorine and oxygen atoms. Structural characterisations of the simulated systems showed that fluoride ions exclusively bond to the calcium modifier cations creating clusters within the glass structure and therefore decreasing the bioactivity of fluoridated phosphate glasses, making them less suitable for biomedical applications.

Medical nutrients obtained from plants have been used in traditional medicine since ancient times, owning to the protective and therapeutic properties of plant extracts and products. Glycyrrhizic acid is one of those that, apart from its therapeutic effect, may contribute to stronger bones, inhibiting bone resorption and improving the bone structure and biomechanical strength. In the present study, we investigated the effect of a bioactive glass (BG) addition to the structure–property relationships of supramolecular assemblies formed by glycyrrhizic acid (GA) and its monoammonium salt (MSGA). FTIR spectra of supramolecular assemblies evidenced an interaction between BG components and hydroxyl groups of MSGA and GA. Moreover, it was revealed that BG components may interact and bond to the carboxyl groups of MSGA. In order to assess their biological effects, BG, MSGA, and their supramolecular assemblies were introduced to a culture of human bone-marrow-derived mesenchymal stromal cells (BMSCs). Both the BG and MSGA had positive influence on BMSC growth, viability, and osteogenic differentiation—these positive effects were most pronounced when BG1d-BG and MSGA were introduced together into cell culture in the form of MSGA:BG assemblies. In conclusion, MSGA:BG assemblies revealed a promising potential as a candidate material intended for application in bone defect reconstruction and bone tissue engineering approaches.

Magnetic bioactive glass-ceramics are biomaterials applied for magnetic hyperthermia in bone cancer treatment, thereby treating the bone tumor besides regenerating the damaged bone. However, combining high bioactivity and high saturation magnetization remains a challenge since the thermal treatment step employed to grow magnetic phases is also related to loss of bioactivity. Here, we propose a new nanocomposite made of superparamagnetic iron oxide nanoparticles (SPIONs) dispersed in a sol-gel-derived bioactive glass matrix, which does not need any thermal treatment for crystallization of magnetic phases. The scanning and transmission electron microscopies, X-ray diffraction, and dynamic light scattering results confirm that the SPIONs are actually embedded in a nanosized glass matrix, thus forming a nanocomposite. Magnetic and calorimetric characterizations evidence their proper behavior for hyperthermia applications, besides evidencing inter-magnetic nanoparticle interactions within the nanocomposite. Bioactivity and in vitro characterizations show that such nanocomposites exhibit apatite-forming properties similar to the highly bioactive parent glass, besides being osteoinductive. This methodology is a new alternative to produce magnetic bioactive materials to which the magnetic properties only rely on the quality of the SPIONs used in the synthesis. Thereby, these nanocomposites can be recognized as a new class of bioactive materials for applications in bone cancer treatment by hyperthermia.

The advent of mesoporous bioactive glasses (MBGs) led to the emergence of a new class of multifunctional, nanostructured biomaterials that show great promise as smart platforms for achieving bone regeneration, local drug delivery, and therapeutic ion release. However, the development of hierarchical macro-/mesoporous three-dimensional scaffolds based on MBGs still remains a challenge. The use of additive manufacturing techniques, especially robocasting, has the potential to improve the processing of these materials, making it easier preserving their functional properties. This chapter discusses the major issues related to robocasting of MBGs, providing an up-to-date contribution to the scientists working in the field of bioactive materials manufacturing.

3D printing emerged as a potential game-changer in the field of biomedical engineering. Robocasting in particular has shown excellent capability to produce custom-sized porous scaffolds from pastes with suitable viscoelastic properties. The materials and respective processing methods developed so far still need further improvements in order to obtain completely satisfactory scaffolds capable of providing both the biological and mechanical properties required for successful and comprehensive bone tissue regeneration. This work reports on the sol-gel synthesis of an alkali-free bioactive glass and on its characterization and processing ability towards the fabrication of porous scaffolds by robocasting. A two-fold increase in milling efficiency was achieved by suitably adjusting the milling procedures. The heat treatment temperature exerted a profound effect on the surface area of mesoporous powders. Robocasting inks containing 35 vol.% solids were prepared, and their flow properties were characterized by rheological tests. A script capable of preparing customizable CAD scaffold geometries was developed. The printing process was adjusted to increase the technique’s resolution. The mechanical properties of the scaffolds were assessed through compressive strength tests. The biomineralization ability and the biological performance were assessed by immersing the samples in simulated body fluid (SBF) and through MTT assays, respectively. The overall results demonstrated that scaffolds with macro porous features suitable for bone ingrowth (pore sizes of ~340 μm after sintering, and a porosity fraction of ~70%) in non-load-bearing applications could be successfully fabricated by 3D printing from the bioactive glass inks. Moreover, the scaffolds exhibited good biomineralization activity and good biocompatibility with human keratinocytes, suggesting they are safe and thus suited for the intended biomedical applications.

In bone tissue engineering, ceramics have been the choice due to their excellent biological properties. But the paradigm changed with the discovery of bioactive glasses (BGs) in 1969 by Larry Hench and co-workers, due to their ability to bond to living tissues through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. Among a number of tested compositions, the one exhibiting the highest bioactivity index is the well-known trademarked 45S5 Bioglass®. The topic received increasing attention particularly after 1985 when this material entered in the market of biomedical devices, inspiring many other investigations aiming at further exploring the in vitro and in vivo performances of this BG, or developing other related BG compositions. The research efforts gradually revealed a number of shortcomings of 45S5 Bioglass®, mostly derived from its high sodium content, initially intended to decrease the melting temperature and accelerating the degradation of the silicate network over time. But the extensive release of sodium from 45S5 Bioglass® in the biological fluids creates a high pH cytotoxic environment. Other serious drawbacks include a fast degradation rate, and a poor sintering ability, which hinders the reliable fabrication of porous scaffolds. Therefore, sol-gel was regarded as an attractive alternative to prepare alkali-free BG compositions. The process uses inorganic and/or organic precursors, which undergo hydrolysis and condensation at room-temperature, being less costly. When properly conducted, the sol-gel process might result in amorphous structures with all the components intimately mixed at the atomic scale. Moreover, developing new better performing materials for bone tissue engineering is a growing concern, as the ageing of the world’s population leads to lower bone density and osteoporosis. This work describes the sol-gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO2 – 34 CaO – 4 MgO – 2 P2O5 (mol%) was prepared using acidified distilled water as single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The results of XRD of samples calcined within the temperature range from 600-900 ºC demonstrated that amorphous nature was maintained until 800 ºC, followed by partial crystallization at 900 ºC. The specific surface area, an important factor in osteoconduction, was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m2/g at 600 ºC down to 2.2 ± 0.1 m2/g at 900 ºC, being accompanied consistent changes in average pore size and agreeing pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering.

A modified 45S5 Bioglass® containing 2 mol% alumina and 2 mol% strontium oxide was prepared. In vitro bioactivity in powder and monolithic samples was conducted. Fourier transform infrared analysis and pH change in simulated body fluid were investigated for powder samples after 480 min of immersion. Additionally, X-ray diffraction and scanning electron microscopy after 7 and 14 days of immersion in simulated body fluid were investigated for monolithic samples. The formation of phosphate and carbonate phase precursors of hydroxycarbonate apatite was observed after 480 min for powder samples, and the hydroxycarbonate apatite pattern and morphology were confirmed after 7 days of immersion for monolithic samples. It seems that changes in composition did not affect reactivity but caused a decrease in the maxima of pH. Cytotoxicity and cell viability obtained by using the NCTC clone 929 cell line did not show any significant loss of cell viability or cytotoxicity. Moreover, after overnight incubation, the samples demonstrated safe disinfection for Escherichia coli. For these reasons, the use of these new bioactive glasses can be considered a promising alternative for the reconstruction of bone defects and even for the treatment and suppression of bone infections., This research was performed with support from the Brazilian government through the funding agencies CAPES (CsF/PDSE-Project No 88881.189953/2018–01), CNPq (GD-Project No 142172/2016–2, Universal Research Project No 481260/2012–9 and PD. 312135/2016–5) and FAPESP (Project No 1999/01924–2).

Orientador: Americo Bortolazzo Correr Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba Resumo: O objetivo deste estudo foi avaliar o ângulo de contato, a habilidade de penetração e potencial de remineralização de infiltrantes resinosos contendo partículas bioativas. Foram utilizados dois infiltrantes experimentais: TEGDMA (100% de trietileno glicol dimetacrilato) e T/B (75% de TEGDMA e 25% de bisfenol glicidil dimetacrilato etoxilado - BisEMA), além do infiltrante Icon©. A estas bases adicionou-se partículas de biovidro de fosfossilicato de cálcio e sódio (Bag45s5), ou nanopartículas de hidroxiapatita (nHap), nas concentrações de 0, 10 e 15%vol. O ângulo de contato foi avaliado em esmalte bovino pelo método da gota séssil em viscosímetro com câmera acoplada, sendo calculada a média de três medidas para cada espécime (n=6). Para avaliação da habilidade de penetração, lesões subsuperficiais semelhantes à cárie foram produzidas em esmalte na face oclusal de molares humanos hígidos e infiltradas com os infiltrantes resinosos. A penetração dos materiais foi verficada em fatias obtidas dessas coroas, por meio de microscopia confocal de varredura a laser (n=3). Para a avaliação do potencial de remineralização, lesões subsuperficiais semelhantes à cárie foram produzidas em esmalte na face vestibular de coroas de molares humanos e infiltradas pelos infiltrantes resinosos. Essas coroas foram submetidas à ciclagem de pH (solução Des/Re) por um mês. A microdureza Knoop (KHN) foi avaliada a 20, 40, 60, 80 e 100 ?m da superfície externa do esmalte, em 3 linhas (5, 100 e 200 ?m distante da lesão) (n=5). Para auxílio na avaliação de remineralização das partículas, a morfologia e o tamanho das mesmas foram analisadas por microscopia eletrônica de transmissão e varredura (MET e MEV), enquanto sua estrutura cristalina foi analisada por difração de raios X (DRX). Os dados referentes a ângulo de contato e habilidade de penetração foram avaliados quanto à normalidade e submetidos à ANOVA dois-fatores e teste de Tukey (?=0,05). Os dados referentes ao potencial de remineralização foram submetidos aos testes de Friedman e Kruskal-Wallis (?=0,05). Os resultados mostraram que a adição de 10 e 15% de nHap reduziu o ângulo de contato do Icon® e a adição de 15% de nHap reduziu o ângulo de contato do T/B. TEGDMA apresentou ângulo de contato menor que Icon® nos grupos sem adição de partículas e valores menores que Icon® e T/B nos grupos com adição de 15% de Bag45s5. T/B apresentou menores valores que Icon® para grupos com adição de 15% nHap. A adição de partículas não interferiu na habilidade de penetração dos infiltrantes. Todos os grupos com matriz resinosa T/B apresentaram habilidade de penetração inferior aos infiltrantes TEGDMA e Icon®. Icon© e T/B + Bag45s5 15%vol apresentaram diferentes valores de KHN para os pontos avaliados intra-grupo, em ambos foi verificado maior dureza nos pontos mais profundos do esmalte. Icon© + Bag45s5 10%vol mostrou, em vários pontos, valores de KHN mais baixos que Icon©, T/B + nHap 10%vol, T/B + Bag45s5 10%vol e T/B + nHap 15%vol. Assim, concluiu-se que adição de nHap reduz o ângulo de contato de Icon® e T/B. A adição das partículas nHap e Bag45s5 não interfere na habilidade de penetração do Icon®, TEGDMA e T/B. E o TEGDMA e o Icon® apresentam melhor penetrabilidade que T/B. A aplicação do infiltrante T/B com adição de Bag45s5 15%vol confere um melhor padrão de remineralização às áreas mais profundas do esmalte, em relação às áreas superficiais. A adição das partículas nHap e Bag45s5 nas concentrações 10%vol e 15%vol não aumenta o potencial de remineralização dos infiltrantes Icon©, TEGDMA e T/B Abstract: The aim of this study was to evaluate the contact angle, the penetration ability and the remineralization potential of resin infiltrants containing bioactive particles addition. Two experimental infiltrants made with TEGDMA (100% triethylene glycol dimethacrylate) or T/B (75% TEGDMA and 25% ethoxylated bisphenol A glycol dimethacrylate - BisEMA), and the commercially available infiltrant Icon© were used. To these materials it was added 0, 10 or 15v% of a sodium calcium phosphosilicate bioglass particles (Bag45s5), or hydroxyapatite nanoparticles (nHap). The contact angle was evaluated on bovine enamel by the sessile drop method in a coupled-camera viscometer. The mean of three measurements for each specimen was calculated (n=6). For penetration ability evaluation, caries-like subsurface lesions were produced in the enamel of occlusal face of human sound molar crowns and infiltrated with resin infiltrants. The materials penetration was verified in slices obtained from these crowns, by means of confocal laser scanning microscopy (n=3). For remineralization potential evaluation, artificial caries was produced in the enamel of vestibular face of human crowns, where infiltrants were applied. These crowns went through pH cycling process (DS-RS) for a month. Knoop microhardness (KHN) was measured at 20, 40, 60, 80 and 100?m from the outer enamel surface, in 3 rows (5, 100 and 200?m to lesion) (n=5). To aid in the evaluation of particle remineralization, particles morphology and dimension were analyzed by transmission and scanning electron microscopies (TEM and SEM), while its crystal structure was analyzed by X-ray diffraction (XRD). Contact angle and penetration ability data were checked for normality and submitted to two-way ANOVA and Tukey's test (? = 0.05). Remineralization potential data was submitted to Friedman and Kruskal-Wallis tests (?=0.05). The results showed that addition of 10 and 15v% nHap significantly decreased contact angle values for Icon®, and addition of 15v% nHap significantly decreased contact angle values for T/B. TEGDMA presented lower contact angle values than Icon® in the groups without particles and lower values than Icon® and T/B in 15v% Bag45s5 groups. T/B presented lower contact angle values than Icon® for groups with addition of 15v% nHap. The addition of particles did not interfere with the penetration ability of infiltrants. All groups with T/B resin matrix presented lower penetration ability than those with TEGDMA and Icon®. Icon© and T / B + Bag45s5 15v% showed differences in KHN values according to the intragroup evaluated sites, in both was verified higher hardness pattern at deeper sites. Icon© + Bag45s5 10v% showed, in several sites, lower KHN values than Icon©, T/B + nHap 10v%, T/B + Bag45s5 10v% and T/B + nHap 15v%. Thus, it was concluded that nHap addition reduces the contact angle of Icon® and T/B. The addition of nHap and Bag45s5 particles does not interfere with the penetration ability of Icon®, TEGDMA and T/B. TEGDMA and Icon® have better penetrability than T/B. T/B + Bag45s5 15v% presents higher KHN in deeper enamel areas. The addition of nHap and Bag45s5 at 10 and 15v% in Icon©, TEGDMA and T/B did not increase their remineralization potential Doutorado Materiais Dentários Doutor em Materiais Dentários CAPES 0878/2018 CNPQ 141962/2016-0

Regenerative medicine is a field that aims to influence and improvise the processes of tissue repair and restoration and to assist the body to heal and recover. In the field of hard tissue regeneration, bio-inert materials are being predominantly used, and there is a necessity to use bioactive materials that can help in better tissue–implant interactions and facilitate the healing and regeneration process. One such bioactive material that is being focused upon and studied extensively in the past few decades is bioactive glass (BG). The original bioactive glass (45S5) is composed of silicon dioxide, sodium dioxide, calcium oxide, and phosphorus pentoxide and is mainly referred to by its commercial name Bioglass. BG is mainly used for bone tissue regeneration due to its osteoconductivity and osteostimulation properties. The bioactivity of BG, however, is highly dependent on the compositional ratio of certain glass-forming system content. The manipulation of content ratio and the element compositional flexibility of BG-forming network developed other types of bioactive glasses with controllable chemical durability and chemical affinity with bone and bioactivity. This review article mainly discusses the basic information about silica-based bioactive glasses, including their composition, processing, and properties, as well as their medical applications such as in bone regeneration, as bone grafts, and as dental implant coatings.

Tissue engineering provides great possibilities to manage tissue damages and injuries in modern medicine. The involvement of hard biocompatible materials in tissue engineering-based therapies for the healing of soft tissue defects has impressively increased over the last few years: in this regard, different types of bioceramics were developed, examined and applied either alone or in combination with polymers to produce composites. Bioactive glasses, carbon nanostructures, and hydroxyapatite nanoparticles are among the most widely-proposed hard materials for treating a broad range of soft tissue damages, from acute and chronic skin wounds to complex injuries of nervous and cardiopulmonary systems. Although being originally developed for use in contact with bone, these substances were also shown to offer excellent key features for repair and regeneration of wounds and "delicate" structures of the body, including improved cell proliferation and differentiation, enhanced angiogenesis, and antibacterial/anti-inflammatory activities. Furthermore, when embedded in a soft matrix, these hard materials can improve the mechanical properties of the implant. They could be applied in various forms and formulations such as fine powders, granules, and micro- or nanofibers. There are some pre-clinical trials in which bioceramics are being utilized for skin wounds; however, some crucial questions should still be addressed before the extensive and safe use of bioceramics in soft tissue healing. For example, defining optimal formulations, dosages, and administration routes remain to be fixed and summarized as standard guidelines in the clinic. This review paper aims at providing a comprehensive picture of the use and potential of bioceramics in treatment, reconstruction, and preservation of soft tissues (skin, cardiovascular and pulmonary systems, peripheral nervous system, gastrointestinal tract, skeletal muscles, and ophthalmic tissues) and critically discusses their pros and cons (e.g., the risk of calcification and ectopic bone formation as well as the local and systemic toxicity) in this regard. STATEMENT OF SIGNIFICANCE: Soft tissues form a big part of the human body and play vital roles in maintaining both structure and function of various organs; however, optimal repair and regeneration of injured soft tissues (e.g., skin, peripheral nerve) still remain a grand challenge in biomedicine. Although polymers were extensively applied to restore the lost or injured soft tissues, the use of bioceramics has the potential to provides new opportunities which are still partially unexplored or at the very beginning. This reviews summarizes the state of the art of bioceramics in this field, highlighting the latest evolutions and the new horizons that can be opened by their use in the context of soft tissue engineering. Existing results and future challenges are discussed in order to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers of the biomaterials community.

Bioactive glasses have been widely investigated for their ability to release ions with therapeutic effect. In this paper, a silica based bioactive glass was doped with a low amount of tellurium dioxide (1 and 5 mol%) to confer antibacterial and antioxidant properties. The obtained glasses were characterized in terms of morphology, composition, structure, characteristic temperatures and in vitro bioactivity. Moreover, comprehensive analyses were carried out to estimate the cytocompatibility, the antibacterial and antioxidant properties of Te-doped glasses. The performed characterizations demonstrated that the Te insertion did not interfere with the amorphous nature of the glass, the substitution of SiO2 with TeO2 led to a slight decrease in Tg and a TeO2 amount higher than 1 mol% can induce a change in the primary crystal field. In vitro bioactivity test demonstrated the Te-doped glass ability to induce the precipitation of hydroxyapatite. Finally, the biological characterization showed a strong antibacterial and antioxidant effects of Te-containing glasses in comparison with the control glass, demonstrating that Te is a promising element to enhance the biological response of biomaterials.

Transitioning beyond a trial-and-error based approach for the compositional design of next-generation borosilicate-based bioactive glasses requires a fundamental understanding of the underlying com...

Orientador: Altair Antoninha Del Bel Cury Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba Resumo: O comportamento bioativo em materiais odontológicos tem sido investigado em diversos campos da odontologia. Alguns estudos modificaram com sucesso cerâmicas odontológicas adicionando vidro bioativo (VB), tornando esses materiais capazes de exibir um comportamento bioativo. No entanto, essas composições têm apresentado propriedades mecânicas inferiores que podem estar relacionadas a um tratamento térmico inadequado. Além disso, outras propriedades como solubilidade química, dureza, rugosidade de superfície e estabilidade de cor, que podem ser afetadas, não foram ainda avaliadas. Assim, o objetivo deste estudo foi avaliar propriedades físicas e mecânicas de uma cerâmica feldspática reforçada por leucita modificada por vidro bioativo. Para isso, três composições de cerâmica odontológica (CO) modificada por vidro bioativo 58S foram sintetizados pelo método de sol-gel (VB20: 80% em peso de CO + 20% em peso de VB, VB30: 70% em peso de CO + 30% em peso de VB e VB40: 60% em peso de CO + 40% em peso de VB). Inicialmente, as composições foram caracterizadas por calorimetria exploratória diferencial e sua resistência à flexão biaxial foram testadas após sinterização a diferentes temperaturas (910, 950, 1000 e 1050 °C). Um grupo composto por 100% de CO, sinterizado de acordo com as recomendações do fabricante (910 °C), foi utilizado como grupo de controle. A temperatura de sinterização que promoveu os maiores valores de resistência à flexão para cada composição (VB20 a 950 °C, VB30 a 1000 °C e VB40 a 1050 °C) foram utilizadas para a avaliação do comportamento bioativo, solubilidade química, microdureza, rugosidade de superfície e estabilidade de cor. Para verificação do comportamento bioativo os grupos foram avaliados por difração de raios-X (DRX) e espectroscopia de infravermelho por transformada de Fourier (FTIR) com e sem imersão em fluido corporal simulado (Simulated Body Fluid, SBF) por 21 dias. Para a microdureza (n=5), foram avaliados em um microdurômetro com identador Knoop. A solubilidade (n=10) foi avaliada por imersão em solução de ácido acético a 4% por 16 horas, a rugosidade de superfície (n=10) por um perfilômetro óptico 3D e a estabilidade de cor (n=10) pelo sistema CIEL*a*b*. As composições experimentais mostraram indícios de comportamento bioativo após a imersão em SBF. Todos os grupos experimentais apresentaram resistência à flexão menor do que o grupo controle (p

Agradecimentos: This study was financed by the State of São Paulo Research Foundation (FAPESP) (grant number 2018/04630-2), by FAEPEX UNICAMP through a research grant (3164/18), and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The authors also thank the Oral Biochemistry Laboratory at Piracicaba Dental School at the University of Campinas (UNICAMP) for use of the microbiology facility, and the Brazilian Nanotechnology National Laboratory (LNNano) at the Brazilian Center of Research in Energy and Materials (CNPEM) for use of the CLSM facilities Abstract: Hypothesis: Although bioactive glass (BG) particle coatings were previously developed by different methods, poor particle adhesion to surfaces and reduced biological effects because of glass crystallization have limited their biomedical applications. To overcome this problem, we have untangled, for the first time, plasma electrolytic oxidation (PEO) as a new pathway for the synthesis of bioactive glass-based coating (PEO-BG) on titanium (Ti) materials. Experiments: Electrolyte solution with bioactive elements (Na2SiO3-5H(2)O, C4H6O4Ca, NaNO3, and C3H7Na2O6P) was used as a precursor source to obtain a 45S5 bioglass-like composition on a Ti surface by PEO. Subsequently, the PEO-BG coating was investigated with respect to its surface, mechanical, tribological, electrochemical, microbiological, and biological properties, compared with those of machined and sandblasted/acid-etched control surfaces. Findings: PEO treatment produced a coating with complex surface topography, Ti crystalline phases, superhydrophilic status, chemical composition, and oxide layer similar to that of 4555-6G (similar to 45.0Si, 24.5 Ca, 24.5Na, 6.0P w/v%). PEO-BG enhanced Ti mechanical and tribological properties with higher corrosion resistance. Furthermore, PEO-BG had a positive influence in polymicrobial biofilms, by reducing pathogenic bacterial associated with biofilm-related infections. PEO-BG also showed higher adsorption of blood plasma proteins without cytotoxic effects on human cells, and thus may be considered a promising biocompatible approach for biomedical implants FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES Fechado

Agradecimentos: The authors acknowledge the use of the analytical instrumentation facility at Institute of Chemistry, University of Campinas, which is supported by the State of Paulo. This work was carried out with the support of the São Paulo Research Foundation - FAPESP (Grant: 2016/24372-2, 2010/05394-9) and the National Council for Scientific and Technological Development (CNPq/PIBITI) and the Coordination for the Improvement of Higher Level -or Education-Personnel (CAPES) for the financial support. We also would like to acknowledge Prof. Dr. Antonio Carlos Boschero for providing us with the SkyScan 1278 (FAPESP EMU 2009/54121-8) for the µCT analysis Abstract: Here, we investigated the biocompatibility of a bioactive sodium calcium silicate glass containing 2.6 mol% Nb2O5 (denoted BGPN2.6) and compare the results with the archetypal 45S5 bioglass. The glass bioactivity was tested using a range of in vitro and in vivo experiments to assess its suitability for bone regeneration applications. in vitro studies consisted of assessing the cytocompatibility of the BGPN2.6 glass with bone-marrow-derived mesenchymal stem cells (BM-MSCs). Systemic biocompatibility was verified by means of the quantification of biochemical markers and histopathology of liver, kidneys, and muscles. The glass genotoxicity was assessed using the micronucleus test. The regeneration of a calvarial defect was assessed using both qualitative and quantitative analysis of three-dimensional microcomputed tomography images. The BGPN2.6 glass was not cytotoxic to BM-MSCs. It is systemically biocompatible causing no signs of damage to high metabolic and excretory organs such as the liver and kidneys. No mutagenic potential was observed in the micronucleus test. MicroCT images showed that BGPN2.6 was able to nearly fully regenerate a critical-sized calvarial defect and was far superior to standard 45S5 Bioglass. Defects filled with BGPN2.6 glass showed over 90% coverage compare to just 66% for 45S5 Bioglass. For one animal the defect was completely filled in 8?weeks. These results clearly show that Nb-containing bioactive glasses are a safe and effective biomaterial for bone replacement Resumo: CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP Fechado

The lymphatic system is crucial for the regeneration of many tissues due to its fundamental role in immune cell trafficking, protein transport, and tissue homeostasis maintenance. Strategies stimulating lymphangiogenesis can provide new therapeutic approaches for tissue repair and regeneration (e.g., chronic wound healing). Here, we explored the effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on lymphangiogenesis. The results showed that the extracts of Ce-MBGNs (1, 5, or 10 wt/v%) were non-cytotoxic toward lymphatic endothelial cells (LECs), while they enhanced the proliferation of LECs. Moreover, as evidenced by the scratch wound healing and Transwell migration assays, conditioned media containing the extract of Ce-MBGNs (1 wt/v%) could enhance the migration of LECs in comparison to the blank control and the media containing vascular endothelial growth factor-C (VEGF-C, 50 ng/mL). Additionally, a tube-formation assay using LECs showed that the extract of Ce-MBGNs (1 wt/v%) promoted lymphatic vascular network formation. Western blot results suggested that Ce-MBGNs could induce lymphangiogenesis probably through the HIF-1α/VEGFR-3 pathway. Our study for the first time showed the effects of Ce-MBGNs on stimulating lymphangiogenesis in vitro, highlighting the potential of Ce-MBGNs for wound healing.

The use of bioactive glasses (BGs) has been quite fruitful in hard tissue engineering due to the capability of these materials to bond to living bone. In this work, a melt-derived magnesium (Mg)-doped BG (composition: 45SiO2–3P2O5–26CaO–15Na2O–7MgO–4K2O (mol.%)) was synthesized for being used in bone reconstruction. The prepared BGs were then manufactured as three-dimensional (3D) scaffolds by using the sponge replica approach. The microstructure of the samples was assessed by X-ray diffraction (XRD) and the surface morphology was observed by using scanning electron microscopy (SEM). The in vitro bioactivity and the release of osteo-stimulatory Mg2+ ions from the prepared samples were investigated over 7 days of incubation in simulated body fluids (SBF). In vitro cellular analyses revealed the compatibility of the Mg-doped BGs with human osteosarcoma cells (MG-63 cell line). Moreover, the Mg-doped BGs could induce bone nodule formation in vitro and improve the migratory ability of human umbilical vein endothelial cells (HUVECs). In vivo osteogenic capacity was further evaluated by implanting the BG-derived scaffolds into surgically-created critical-size bone defects in rats. Histological and immunohistological observations revealed an appropriate bone regeneration in the animals receiving the glass-based scaffolds after 12 weeks of surgery. In conclusion, our study indicates the effectiveness of the Mg-doped BGs in stimulating osteogenesis in both in vitro and in vivo conditions.

Due to poor mechanical properties and brittleness of bioactive glasses, the deposition of bioactive glass coatings on bioinert metallic implants for bone regeneration is a promising route to combine the high bioactivity of the glassy phase with the mechanical strength of metallic substrate. The Pulsed Electron Deposition (PED) technique has been recently demonstrated to be an effective method to fabricate highly-adherent and nanostructured bioactive thin films and coatings, with fine control over film composition. In this paper, we investigated the deposition by PED of 45S5 Bioglass ® and of a novel CaO-rich bioactive glass, also containing potassium oxide. Composition, microstructure, surface morphology, wettability and adhesion to the titanium substrate were assessed for both as-deposited and annealed coatings. All samples exhibited a nanostructured surface morphology and high hydrophilicity, both positive features for biological applications. In particular, annealed samples exhibited increased roughness and adhesion degree to the titanium substrate compared to the as-deposited ones. The results showed in this paper suggest that bioactive glass coatings deposited by PED are promising for being further investigated as bioactive coatings for bone implants.

In this research work composite coatings made of alginate and 45S5 bioactive glass particles doped with B, Zn or Sr were synthesized by means of electrophoretic deposition and characterized from morphological, compositional, thermogravimetric, mechanical and electrochemical points of view. The developed coatings were also subjected to in vitro test in SBF solution to evaluate their ability to induce hydroxyapatite precipitation and cytocompatibility evaluation using human primary fibroblasts. The obtained results demonstrated a good homogeneity of the coatings, high adhesion and a protective behavior towards the substrate. The thermogravimetric analysis proved that the glass amount was constant before and after the deposition and all the investigated coatings promoted the deposition of hydroxyapatite but with different kinetics. Since the Zn containing coating showed the best bioactive behavior it was subjected to cytocompatibility test, which demonstrated, after an initial reduction of cell viability, a good cell proliferation and the production of collagen from the ECM. These findings suggest that the obtained coatings are promising materials to coat metallic prosthetic devices.

Most biomaterial-associated infections are caused by opportunistic pathogens and bacteria that are regularly found within the microflora of the implant site. In addition, a biomaterial implant or device remains at risk of infection by hematogenous spread of bacteria disseminated from infections elsewhere in the body or from infected peri-implant tissue in revision surgery. The resulting infections are frequently accompanied by patient morbidity and discomfort and can lead to surgical replacement of the implant after lengthy, unsuccessful attempts to mitigate infections with antibiotic treatments. Therefore, extensive study is aiming to find new infection-resistant antimicrobial biomaterials and coatings for implants and devices to effectively reduce the incidence of biomaterial-associated infections. An overview of the in vitro and in vivo antimicrobial efficacies of the numerous biomaterials currently available is beyond the scope of this review. Herein, we provide a comprehensive review of bioactive glasses as biomaterial delivery systems for antimicrobial agents. Fil: Rivadeneira, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Catolica de Salta. Facultad de Ingeniería E Informatica. Instituto D/estudios Interdiciplinarios En Ingeniería; Argentina Fil: Gorustovich Alonso, Alejandro Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Catolica de Salta. Facultad de Ingeniería E Informatica. Instituto D/estudios Interdiciplinarios En Ingeniería; Argentina

Hydroxyapatite-based composites (HA-C) with bioglass as second phase are usually produced by hot-pressing or pressureless sintering. However, such methods require thermal levels which exceed the crystallization temperature of the glass, with possible negative effects on the bioactivity of the final system. Spark plasma sintering (SPS) is a powerful consolidation technique in terms of both processing time and temperature. In this work SPS has been employed, for the first time, to obtain HA-C with an innovative bioglass as second phase. Such glass was designed to be used whenever a thermal treatment is required, thanks to its low tendency to crystallize. A systematic study is conducted to identify the optimal sintering conditions for preparing highly dense composites and, at the same time, to minimize the crystallization of the glassy phase. The obtained samples are highly bioactive and display higher compactness and hardness with respect to the counterparts produced by conventional sintering methods.

© 2019 Elsevier B.V. In 2014–2015, 61,421 total knee arthroplasties (TKAs) were performed in Canada; an increase of about 20% over 2000–2001. Revision total knee arthroplasties (rTKAs) accounted for 6.8% of TKAs performed between 2014 and 2015, and this is estimated to grow another 12% by 2025. rTKAs are typically more complicated than primary TKAs due to the significant loss of femoral and tibial bone stock. The escalating demand and limitations associated with total knee arthroplasty and their revision drives the development of novel treatments. A variety of materials have been utilized to facilitate regeneration of healthy bone around the site of a knee arthroplasty. The selection of these materials is based on the bone defect size and includes bone grafts, graft substitutes and cements. However, all these materials have certain disadvantages such as blood loss, disease transmission (bone grafts), inflammatory response, insufficient mechanical properties (bone graft substitutes) thermal necrosis and stress shielding (bone cement). Recently, the use of metal augments for large bone defects has attracted attention, however they can undergo fretting, corrosion, and stress shielding. All things considered, this review indicates the necessity of developing augments that have structural integrities and biodegradation rates similar to that of human bone. Therefore, the future of bone loss management may lie in fabricating novel bioactive glass augments as they can promote bone healing and implant stability and can degrade with time.

Bioactive materials, able to induce hydroxyapatite precipitation in contact with body fluids, are of great interest for their bone bonding capacity. . The aim of this paper is to compare bioactive materials with different surface features to verify the mechanisms of action and the relationship with kinetics and type of precipitated hydroxyapatite over time. Four different surface treatments for Ti/Ti6Al4V alloy and a bioactive glass were selected and a different mechanism of bioactivity is supposed for each of them. Apart from the conventional techniques (FESEM, XPS and EDX), less common characterizations (zeta potential measurements on solid surfaces and FTIR chemical imaging) were applied. The results suggest that the OH groups on the surface have several effects: the total number of the OH groups mainly affects hydrophilicity of surfaces, while the isoelectric points, surface charge and ions attraction mainly depend on OH acidic/basic strength. Kinetics of hydroxyapatite precipitation is faster when it involves a mechanism of ion exchange while it is slower when it is due to electrostatic effects . The electrostatic effect cooperates with ion exchange and it speeds up kinetics of hydroxyapatite precipitation. Different bioactive surfaces are able to differently induce precipitation of type A and B of hydroxyapatite, as well as different degrees of crystallinity and carbonation. STATEMENT OF SIGNIFICANCE: The bone is made of a ceramic phase (a specific type of hydroxyapatite), a network of collagen fibers and the biological tissue. A strong bond of an orthopedic or dental implant with the bone is achieved by bioactive materials where precipitation and growth of hydroxyapatite occurs on the implant surface starting from the ions in the physiological fluids. Several bioactive materials are already known and used, but their mechanism of action is not completely known and the type of precipitated hydroxyapatite not fully investigated. In this work, bioactive titanium and bioglass surfaces are compared through conventional and innovative methodologies. Different mechanisms of bioactivity are identified, with different kinetics and the materials are able to induce precipitation of different types of hydroxyapatite, with different degree of crystallinity and carbonation.

The effects of testing solutions and conditions on hydroxyapatite (HAp) formation as a means of in vitro bioactivity evaluation of B2O3 containing 45S5 bioactive glasses were systematically investigated. Four glass samples prepared by the traditional melt and quench process, where SiO2 in 45S5 was gradually replaced by B2O3 (up to 30%), were studied. Two solutions: the simulated body fluid (SBF) and K2HPO4 solutions were used as the medium for evaluating in vitro bioactivity through the formation of HAp on glass surface as a function of time. It was found that addition of boron oxide delayed the HAp formation in both SBF and K2HPO4 solutions, while the reaction between glass and the K2HPO4 solution is much faster as compared to SBF. In addition to the composition and medium effects, we also studied whether the solution treatments (e.g., adjusting to maintain a pH of 7.4, refreshing solution at certain time interval, and no disturbance during immersion) affect HAp formation. Fourier transform infrared spectrometer (FTIR) equipped with an attenuated total reflection (ATR) sampling technique and scanning electron microscopy (SEM) were conducted to identify HAp formation on glass powder surfaces and to observe HAp morphologies, respectively. The results show that refreshing solution every 24 h produced the fastest HAp formation for low boron-containing samples when SBF was used as testing solution, while no significant differences were observed when K2HPO4 solution was used. This study thus suggests the testing solutions and conditions play an important role on the in vitro bioactivity testing results and should be carefully considered when study materials with varying bioactivities., Graphical abstract Image 1, Highlights • Four bioactive glass compositions with different levels of B2O3 to SiO2 substitution in 45S5 were studied. • The effect of solution type and solution condition on in vitro bioactivity testing were studied. • Results show that boron oxide addition increases the tendency of crystallization of the 45S5 bioactive glasses. • Testing using K2HPO4 solution show faster speed of hydroxyapatite formation than SBF. • Solution conditions play an important role on in vitro SBF bioactivity testing.

Different bioactive glasses (BGs), bioceramics, and their composites were extensively analyzed in terms of biological responsiveness and angiogenic potential. In particular several inorganic materials were considered, namely the widely used 45S5 BG, an experimental BG with low tendency to crystallize, other three experimental BGs doped with strontium and/or magnesium, a commercial hydroxyapatite (HA), and two BG-HA composites (with varying percentages of BG and HA). All these materials were ad hoc prepared and in vitro tested by means of an extensive biological analysis, such as MC3T3-E1 cell viability and proliferation by direct contact assay, alkaline phosphatase activity, mineralized matrix deposition analysis by alizarin red staining, as well as evaluation of angiogenic potential and vascular endothelial growth factor release using ST2 cells. Thus, this investigation allows gaining a deeper insight into the biological performance of different inorganic material categories, and to critically compare the different possible solutions, as bone/tissue substitutes for enhanced healing and repair, in terms of bioactivity and regenerative potential.

Journal of The Dental Association of Thailand, 69, 1, 060-069

Agradecimentos: The authors acknowledge the use of the analytical instrumentation facility at the Institute of Chemistry, the University of Campinas, which is supported by the State of Paulo. This work was carried out with the support of the São Paulo Research Foundation - FAPESP (Grant: 2010/05394-9, 2010/12376-5, 2010/00863-0, 2011/09240-9, and 2011/17877-7) and the National Council for Scientific and Technological Development (CNPq/PIBITI) for the financial support. The authors would like to thank Brazilian Nanotechnology National Laboratory (LNNano) for technical support during SEM and AFM analyzes especially Dr. Carlos Alberto Rodrigues Costa for his technical assistance with AFM analysis Abstract: In vitro and in vivo experiments were undertaken to evaluate the solubility, apatite-forming ability, cytocompatibility, osteostimulation, and osteoinduction for a series of Nb-containing bioactive glass (BGNb) derived from composition of 45S5 Bioglass. Inductively coupled plasma optical emission spectrometry (ICP-OES) revealed that the rate at which Na, Ca, Si, P, and Nb species are leached from the glass decrease with the increasing concentration of the niobium oxide. The formation of apatite as a function of time in simulated body fluid was monitored by 31P Magic Angle Spinning (MAS) Nuclear magnetic resonance spectroscopy. Results showed that the bioactive glasses: Bioglass 45S5 (BG45S5) and 1 mol%-Nb-containing-bioactive glass (BGSN1) were able to grow apatite layer on their surfaces within 3 h, while glasses with higher concentrations of Nb2O5 (2.5 and 5 mol%) took at least 12 h. Nb-substituted glasses were shown to be compatible with bone marrow-derived mesenchymal stem cells (BMMSCs). Moreover, the bioactive glass with 1 mol% Nb2O5 significantly enhanced cell proliferation after 4 days of treatment. Concentrations of 1 and 2.5 mol% Nb2O5 stimulated osteogenic differentiation of BMMSCs after 21 days of treatment. For the in vivo experiments, trial glass rods were implanted into circular defects in rat tibia in order to evaluate their osteoconductivity and osteostimulation. Two morphometric parameters were analyzed: (a) thickness of new-formed bone layer and (b) area of new-formed subperiostal bone. Results showed that BGNb bioactive glass is osteoconductive and osteostimulative. Therefore, these results indicate that Nb-substituted glass is suitable for biomedical applications CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP Fechado

The fight against cancer is an old challenge for mankind. Apart from surgery and chemotherapy, which are the most common treatments, use of radiation represents a promising, less invasive strategy that can be performed both from the outside or inside the body. The latter approach, also known as brachytherapy, relies on the use of implantable beta-emitting seeds or microspheres for killing cancer cells. A set of radioactive glasses have been developed for this purpose but their clinical use is still mainly limited to liver cancer. This review paper provides a picture of the biomedical glasses developed and experimented for brachytherapy so far, focusing the discussion on the production methods and current limitations of the available options to their diffusion in clinical practice. Highly-durable neutron-activatable glasses in the yttria-alumina-silica oxide system are typically preferred in order to avoid the potentially-dangerous release of radioisotopes, while the compositional design of degradable glass systems suitable for use in radiotherapy still remains a challenge and would deserve further investigation in the near future.

Many type of oxide substituted glass-ceramics like strontium, cobalt, barium and titanium have shown bioactivity with improved mechanical properties. The present work reports the in vitro bioactivity and mechanical properties of nickel oxide substituted in bioactive glass-ceramic and results were compared with 45S5 bioactive glass-ceramic. Bioactive glass ceramics were processed through controlled crystallization of their respective bioactive glasses. The formed crystalline phases in bioactive glass-ceramics were identified using X-ray diffraction (XRD) analysis. The formation of HA layer was assessed by immersing them in the simulated body fluid (SBF) for different soaking periods. The formation of hydroxyapatite was confirmed by FTIR spectrometry, SEM and pH measurement. Densities and mechanical properties of the samples were found to increase considerably with an increasing the concentration of nickel oxide. A decrease in glass transition temperature (Tg) with NiO addition showed that the nickel oxide had acted as an intermediate in smaller quantities in the bioactive glass. The cell culture studies demonstrated that the samples containing low concentration of NiO from 0 to 1.65 mol% were non-cytotoxic against osteoblast cells. Finally, this investigation clearly concluded that NiO doped bioactive glass would be potential biomaterials for biomedical applications.

Densification and crystallization phenomena taking place when a recently developed CaO-rich bioactive glass and conventional 45S5 Bioglass ® are processed by Spark Plasma Sintering (SPS) are examined. Fully dense and wholly amorphous products can be obtained from the new glass composition at 730 °C after 2 min dwell time. Moreover, temperatures equal or higher than 830 °C are needed to induce crystallization (α- and β-CaSiO 3 ) in the parent glass. Conversely, Na 6 Ca 3 Si 6 O 18 crystals are formed in sintered 45S5 samples produced under optimal conditions (550 °C, 2 min), although the glassy character is still preserved. Products resulting from the innovative glass powders generally display higher hardness and local elastic modulus. Devitrification also provides improvements in this system. In contrast, mechanical properties become slightly worsen when classical bioglass is processed at 600 °C. This can be probably associated to the corresponding decrease in compactness which, apparently, overcomes the benefits arising from the crystallization progress.

Bone defects in load bearing areas require bone reconstruction with strong biomaterial having mechanical characteristics like cortical bone. Bioceramics are biomaterials that support bone formation as well as provide adequate mechanical properties. A strontium substitution of the bioceramic is expected to further increase its bioactivity by enhancing osteogenesis and protect the bone from osteoclastic resorption. The study involves development, characterization and in vivo testing of a newly developed strontium substituted hydroxyapatite based bioceramic scaffold (SrHAB) with sufficient biomechanical properties. Optimal concentration of strontium ion required for enhanced osteogenic differentiation was identified by comparing three compositions of SrHAB scaffold; namely Sri10HAB, Sr30HAB and Sr50 HAB for their Alkaline phosphatase activity in vitro. The selected Sr10HAB scaffold demonstrated in vivo bone formation with osteogenic differentiation of stromal derived mesenchymal stem cells (MSC) from human and ovine sources in ectopic and ovine models. Thus, Sr10HAB scaffold has a potential for application in load bearing bone requirements of orthopaedics and dentistry.

This study investigated the human dentin microhardness (MH) and the MTA Fillapex&reg, (Fillapex) and AH Plus&reg, (AH) bond strength (BS) to dentin after using calcium hydroxide (Ca(OH)2) and bioactive glasses (45S5 and an experimental niobium phosphate bioactive glass (NbG)) as intracanal medications. For the MH test dentin slices were filled with medications and were submitted to Knoop MH (KHN) test (at day-0 (baseline data/without medication) and at day-15 (after using medication)). For the BS test, after medications had remained for 15 days in the roots, dentin slices were obtained and filled with the sealers. Seven days later, sealer BS to dentin was measured by push-out test (MPa). Data were statistically analyzed. Failure mode was visually assessed. The use of NbG, 45S5 for 15 days, increased the dentin MH and reduced the BS between AH sealer and dentin, but did not interfere with the Fillapex BS.

A novel bioglass composition (BGMS10), containing strontium and magnesium and characterized by an ultra-high crystallization temperature, is here employed for the first time to produce different composites with the addition of specific amounts of hydroxyapatite. After an investigation of the samples' bioactivity in vitro in a simulated body fluid solution (SBF) – according to a widely used protocol –, the biocompatibility of the new materials was tested with respect to murine fibroblasts both by direct and indirect tests, in order to evaluate possible cytotoxic effects of the materials' eluates. Although none of the samples were cytotoxic and their bioactivity in SBF increased with the increasing amount of the glass in the composite, thus showing the best performance in the case of pure BGMS10 glass, the findings of the biological investigation did not confirm those arising from the SBF assay. Surprisingly, while the composites with the lowest glass amount showed an enhanced biocompatibility in direct tests, on the contrary their biological responsiveness is typically lower in the indirect ones, based on filtered materials' extracts. This fact could be ascribed to the high release of particulate from the composites, which are more porous than the glassy samples: in fact, such pronounced dissolution may affect both the cell viability and the absorbance readings used in the colorimetric assays. The pure BGMS10 glass showed the best biological response only in the cell proliferation test (which is an indirect contact test), being able to stimulate cell proliferation in particular after 24 h. For these reasons, when considering bioactive glasses and bioglass-based composites, the results of direct cell culture assays should be integrated with those obtained by indirect ones, while the findings regarding the in vitro bioactivity in SBF should be interpreted with great care.