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PDF file - 427K, Effects of the combination cetuximab plus fingolimod on tumor growth of mice xenografted with GEO-CR resistant tumors

PDF file - 5320K, Validation of antibodies for analysis of SphK1 expression on FFPE colorectal cancer tissues

PDF file - 503K, Effects of SphK1 modulation on cetuximab sensitivity in resistant colorectal cancer cell lines

PDF file - 1047K, Effects of the combination cetuximab plus fingolimod on apoptosis of GEO-CR tumor xenografts

PDF file - 2068K, Correlation of SphK1 expression with clinical data in colorectal cancer patients

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PDF file - 483K, Effects of SphK1 inhibition by DMS on cetuximab sensitivity in resistant colorectal cancer cell lines

PDF file - 357K, Sensitivity to cetuximab of a panel of human colorectal cancer cell lines

Purpose: Although the anti–EGF receptor (EGFR) monoclonal antibody cetuximab is an effective strategy in colorectal cancer therapy, its clinical use is limited by intrinsic or acquired resistance. Alterations in the “sphingolipid rheostat”—the balance between the proapoptotic molecule ceramide and the mitogenic factor sphingosine-1-phosphate (S1P)—due to sphingosine kinase 1 (SphK1) overactivation have been involved in resistance to anticancer-targeted agents. Moreover, cross-talks between SphK1 and EGFR-dependent signaling pathways have been described.Experimental design: We investigated SphK1 contribution to cetuximab resistance in colorectal cancer, in preclinical in vitro/in vivo models, and in tumor specimens from patients.Results: SphK1 was found overexpressed and overactivated in colorectal cancer cells with intrinsic or acquired resistance to cetuximab. SphK1 contribution to resistance was supported by the demonstration that SphK1 inhibition by N,N-dimethyl-sphingosine or silencing via siRNA in resistant cells restores sensitivity to cetuximab, whereas exogenous SphK1 overexpression in sensitive cells confers resistance to these agents. Moreover, treatment of resistant cells with fingolimod (FTY720), a S1P receptor (S1PR) antagonist, resulted in resensitization to cetuximab both in vitro and in vivo, with inhibition of tumor growth, interference with signal transduction, induction of cancer cells apoptosis, and prolongation of mice survival. Finally, a correlation between SphK1 expression and cetuximab response was found in colorectal cancer patients. Clin Cancer Res; 19(1); 138–47. ©2012 AACR.

PDF file - 908K, Multivariate analysis correlating the response to cetuximab-based regimens to different factors

Hybrid diamond-like carbon (DLC) with incorporated titanium dioxide (TiO2) nanoparticle coatings have low friction coefficient, high wear resistance, high hardness, biocompatibility, and high chemical stability. They could be employed to modify biomedical alloys surfaces for numerous applications in biomedical engineering. Here we investigate for the first time the in vivo inflammatory process of DLC coatings with incorporated TiO2nanoparticles. TiO2-DLC films were grown on AISI 316 stainless-steel substrates using plasma-enhanced chemical vapor deposition. The coated substrates were implanted in CF1 mice peritoneum. The in vivo cytotoxicity and biocompatibility of the samples were analyzed from macrophage lavage. Analysis in the first weeks after implantation could be helpful to evaluate the acute cytotoxicity generated after a possible inflammatory process. The in vivo results showed no inflammatory process. A significant increase in nitric oxide production on the uncoated substrates was confirmed through cytometry, and the coated substrates demonstrated biocompatibility. The presence of TiO2nanoparticles enhanced the wound healing activity, due to their astringent and antimicrobial properties. DLC and TiO2-DLC coatings were considered biocompatible, and the presence of TiO2nanoparticles reduced the inflammatory reactions, increasing DLC biocompatibility.

The engineering of multifunctional surgical bactericidal nanofibers with inherent suitable mechanical and biological properties, through facile and cheap fabrication technology, is a great challenge. Moreover, hernia, which is when organ is pushed through an opening in the muscle or adjacent tissue due to damage of tissue structure or function, is a dire clinical challenge that currently needs surgery for recovery. Nevertheless, post-surgical hernia complications, like infection, fibrosis, tissue adhesions, scaffold rejection, inflammation, and recurrence still remain important clinical problems. Herein, through an integrated electrospinning, plasma treatment and direct surface modification strategy, multifunctional bactericidal nanofibers were engineered showing optimal properties for hernia repair. The nanofibers displayed good bactericidal activity, low inflammatory response, good biodegradation, as well as optimal collagen-, stress fiber- and blood vessel formation and associated tissue ingrowth in vivo. The disclosed engineering strategy serves as a prominent platform for the design of other multifunctional materials for various biomedical challenges., Afewerki et al. employ integrated electrospinning, plasma treatment and direct surface modification strategy to engineer multifunctional bactericidal nanofibers for use in hernia repair. In a mouse model, they demonstrate that these nanofibers display good biological performance with low inflammatory response, good biodegradation and optimal collagen and blood vessel formation and tissue growth.

Aim: Comparison of first-line FOLFIRINOX (FFN) and nab-paclitaxel plus gemcitabine (NabGem) in patients with metastatic pancreatic ductal adenocarcinoma. Patients & methods: The authors analyzed data from 160 patients with metastatic pancreatic adenocarcinoma receiving first-line FFN (n=43) or NabGem (n=117). Results: FFN and NabGem were similar in median progression-free survival (24.43 vs 26.28weeks; hazard ratio [HR]: 0.88) and medial overall survival (47.43 vs 42.86weeks; HR: 0.90). Of the 43 patients receiving FFN, 26 (60.4%) were treated with second-line NabGem; 14/117 (12.0%) patients receiving NabGem received second-line FFN (p&nbsp

TiN granular thin films were deposited on SiO2 substrates using cathodic cage plasma nitriding (CCPN) and SEM images, roughness analysis, contact angle measurements, and X-ray diffraction (XRD) were employed to characterize the structure of these films varying time and temperature of the process. Results have shown an inverse relationship between roughness and contact angle. Thin films with low roughness have presented higher contact angle values, and the opposite was observed in the films with more prominent or more grains per area. TiN is a hydrophobic material, and the decrease of contact angle value presented in some films produced occur due to modification of the morphological characteristics, which the roughness measurements and hysteresis of contact angle confirmed it, specifically, for samples synthesized at 2h and 350°C, the roughness is the smallest, and the contact angle is the largest [(111.23±8.87)°]. This connection between roughness and contact angle is essential, and it can be used to describe and characterize the most types of thin films produced by plasma deposition and to infer the surface modifications with different atmospheres of treatment.

This study aimed to analyze the fluoride concentrations in different dentifrices with antimicrobial and natural molecules marketed in Brazil. Thus, 12 dentifrices were selected to be analyzed for the concentration of total fluoride (TF), total soluble fluoride (TSF) and ionizable fluoride (IF). Two tubes of each brand were purchased at different locations. The samples were analyzed in duplicates using an ion-specific electrode and the concentrations were determined in μg F/g. The TF of all calcium carbonate dentifrices showed averages below 1500 ppm F. Regarding TSF, only one toothpaste had an average above 1000 ppm F−, while the IF values ​​were almost 500 ppm F. In the analysis of fluoride in dentifrices which present silica as abrasive, the TF presented averages below 1500 ppm F, while the TSF all presented averages close to 1000 ppm F−, and the IF values ​​varied from close to 500 ppm to more than 1000 ppm F. In dentifrices whose formulation contained calcium carbonate associated with silica or other formulations such as sodium bicarbonate, the TF, TSF, and IF values were all above 1000 ppm F. The evaluated dentifrices generally showed TF concentrations lower than those declared on the packaging; however, the TSF content remained close to 1000 ppm F. It can be concluded that the analyzed dentifrices with antimicrobial molecules showed values ​​close to those suggested regarding anti-caries effect.

Background: CDK4/6 inhibitors have been approved in combination with endocrine therapy for the treatment of estrogen receptor positive (ER+) metastatic breast cancer. The goal of this study was to discover mechanisms of resistance to ER antagonists alone and in combination with CDK4/6 inhibitors. Results: p21-activated kinase 1 (PAK1) is a serine/threonine kinase amplified in several human cancer types. Specifically, the survey of TCGA for copy number alterations and/or expression showed PAK1 amplification and/or overexpression in ~23% of ER+ breast cancer. To test the hypothesis that PAK1-amplification is related to CDK4/6 inhibitors resistance, we generated two ER+ breast cancer cell lines T47D (harbouring PAK1 amplification) and MCF7 (non PAK1-amplified) resistant to the combination of fulvestrant (ER downregulator) and abemaciclib (CDK4/6 inhibitor), namely T47DFAR and MCF7FAR. T47DFAR and MCF7FAR were obtained, exposing the parental cells to increasing doses of drugs. Interestingly, only the T47DFAR but not the MCF7FAR showed higher level of PAK1 expression and activation compared to the parental cell line. PAK1 pathway activation was evaluated measuring by immunoblot the levels of phosphorylation of PAK1, MEK, ERK and Beta-Catenin. Moreover, the genomic knockdown of PAK1 through RNAi causes a decrease in cell proliferation of T47DFAR, but not of MCF7FAR and parental cells, suggesting the role of PAK1 as a possible mediator of drug resistance. Conversely, overexpression of PAK1 in MCF7 and T47D parental cells was able to generate resistance to the drug combination. PAK-1 has shown to have a different role in the cytosol as pathways mediator and in the nucleus as transcriptional factor. Our data obtained by subcellular fractionation showed that after treatment with fulvestrant-abemaciclib, PAK1 protein accumulates into the cytosol in T47D-FAR compared to parental T47D, probably mediating an enhancement in cytoplasmatic cell signalling and pathway activation. To univocally demonstrate that PAK1 mediates tumor resistance to fulvestrant-abemaciclib combination, we are generating data from RNA-Seq and whole exome sequencing from T47DFAR and MCF7FAR and the relative parental cell lines. Also, we will assess the efficacy of PAK pharmacological inhibition in overcoming such resistance. Conclusions: In conclusion, our data suggest the role of PAK1 as a novel therapeutic target in ER+/PAK1-amplified breast cancer model resistant to endocrine therapy and CDK4/6 inhibitors. Citation Format: Stefania Belli, Alberto Servetto, Concetta Di Mauro, Daniela Esposito, Ada Pesapane, Fabiana Napolitano, Antonio Santaniello, Pietro De Placido, Priscilla Cascetta, Annachiara Carratù, Eleonora Mozzillo, Roberta Marciano, Roberto Bianco, Luigi Formisano. Pak1 as a novel mediator of resistance to endocrine therapy and CDK4/6 inhibitors in ER+/PAK-1amplified breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-06-08.

Background The facile preparation of oxygen-generating microparticles (M) consisting of Polycaprolactone (PCL), Pluronic F-127, and calcium peroxide (CPO) (PCL-F-CPO-M) fabricated through an electrospraying process is disclosed. The biological study confirmed the positive impact from the oxygen-generating microparticles on the cell growth with high viability. The presented technology could work as a prominent tool for various tissue engineering and biomedical applications. Methods The oxygen-generated microparticles fabricated through electrospraying processes were thoroughly characterization through various methods such as X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) analysis, and scanning electron microscopy (SEM)/SEM-Energy Dispersive Spectroscopy (EDS) analysis. Results The analyses confirmed the presence of the various components and the porous structure of the microparticles. Spherical shape with spongy characteristic microparticles were obtained with negative charge surface (ζ = -16.9) and a size of 17.00 ± 0.34 μm. Furthermore, the biological study performed on rat chondrocytes demonstrated good cell viability and the positive impact of increasing the amount of CPO in the PCL-F-CPO-M. Conclusion This technological platform could work as an important tool for tissue engineering due to the ability of the microparticles to release oxygen in a sustained manner for up to 7 days with high cell viability.

Background Nanophase surface properties of titanium alloys must be obtained for a suitable biological performance, particularly to facilitate cell adhesion and bone tissue formation. Obtaining a bulk nanostructured material using severe plastic deformation is an ideal processing route to improve the mechanical performance of titanium alloys. By decreasing the grain size of a metallic material, a superior strength improvement can be obtained, while surface modification of a nanostructured surface can produce an attractive topography able to induce biological responses in osteoblastic cells. Methods Aiming to achieve such an excellent synergetic performance, a processing route, which included equal channel angular pressing (ECAP), hot and cold extrusion, and heat treatments, was used to produce a nanometric and ultrafine-grained (UFG) microstructure in the Ti-6Al-7Nb alloy (around of 200 nm). Additionally, UFG samples were surface-modified with acid etching (UFG-A) to produce a uniform micron and submicron porosity on the surface. Subsequently, alkaline treatment (UFG-AA) produced a sponge-like nanotopographic substrate able to modulate cellular interactions. Results After several kinds of biological tests for both treatment conditions (UFG-A and UFG-AA), the main results have shown that there was no cytotoxicity, expressed alkaline phosphatase activity and total protein amounts without statistical differences compared to control. However, the UFG-AA samples presented an attractive effect on the cell membranes, and cell adhesions were preferentially induced as compared with UFG-A. Both conditions demonstrated cell projections, but for UFG-AA, cells were more widely dispersed, and more quantities of filopodia formation could be observed. Conclusion Herein, the reasons for such behaviors are discussed, and further results are presented in addition to those mentioned above.

Background: Several studies proved that anodic oxidation improves osseointegration. This study aimed to optimize osseointegration through anodization in dental implants, obtaining anatase phase and controlled nanotopography. Methods: The division of the groups with 60 titanium implants was: control (CG), sandblasted (SG), anodized (AG): anodized pulsed current (duty cycle 30%, 30 V, 0.2 A and 1000 Hz). Before surgery, surface characterization was performed using Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), X-ray Dispersive Energy Spectroscopy (EDS) and Raman Spectroscopy. For in vivo tests, 10 New Zealand white rabbits received an implant from each group. The sacrifice period was 2 and 6 weeks (n = 5) and the specimens were subjected to computed microtomography (μCT) and reverse torque test. Results: AFM and SEM demonstrated a particular nanotopography on the surface in AG, the anatase phase was proved by Raman spectroscopy. In the μCT and in the reverse torque test, the AG group presented better results than the other groups. Conclusion: The chemical composition and structure of the TiO2 film were positively affected by the anodizing technique, intensifying the biological characteristics in osseointegration.

Different strategies have been employed to provide adequate nutrients for engineered living tissues. These have mainly revolved around providing oxygen to alleviate the effects of chronic hypoxia or anoxia that result in necrosis or weak neovascularization, leading to failure of artificial tissue implants and hence poor clinical outcome. While different biomaterials have been used as oxygen generators for in vitro as well as in vivo applications, certain problems have hampered their wide application. Among these are the generation and the rate at which oxygen is produced together with the production of the reaction intermediates in the form of reactive oxygen species (ROS). Both these factors can be detrimental for cell survival and can severely affect the outcome of such studies. Here we present calcium peroxide (CPO) encapsulated in polycaprolactone as oxygen releasing microparticles (OMPs). While CPO releases oxygen upon hydrolysis, PCL encapsulation ensures that hydrolysis takes place slowly, thereby sustaining prolonged release of oxygen without the stress the bulk release can endow on the encapsulated cells. We used gelatin methacryloyl (GelMA) hydrogels containing these OMPs to stimulate survival and proliferation of encapsulated skeletal myoblasts and optimized the OMP concentration for sustained oxygen delivery over more than a week. The oxygen releasing and delivery platform described in this study opens up opportunities for cell-based therapeutic approaches to treat diseases resulting from ischemic conditions and enhance survival of implants under severe hypoxic conditions for successful clinical translation.

Currently, oxygen supply for in vitro cell culture is one of the major challenges in tissue engineering, especially in three-dimensional (3D) structures, such as polymeric hydrogels, because oxygen is an essential element for cells survival. In this context, oxygen levels must be maintained in articular cartilage to promote the differentiation, viability, and proliferation of chondrocytes due to the low level of oxygen presence in this region. Although some technologies employ oxygen-generating materials to add sufficient oxygen levels, the limitations and challenges of current technologies include the lack of controlled, sustained, and prolonged release of the oxygen. Moreover, the fabrication methods may leave some impurities or residues resulting in toxicity to the cells. “Click” chemistry is a facile, versatile, and compatible chemical strategy to engineer hydrogels for tissue engineering applications. Herein, we disclose the engineering of oxygen-generating microparticles in chondrocytes-laden hydrogels through a versatile catalyst-free tetrazine and norbornene inverse electron demand Diels‒Alder (iEDDA) click reaction. The hydrogels combine chondroitin sulfate (CS) and poly(ethylene glycol) (PEG) crosslinked in situ, displaying tunable rheological and mechanical properties, for sustained and prolonged oxygen-release. Gene expression analysis of the chondrocytes by real-time reverse transcription polymerase chain reaction (RT-PCR) demonstrated promising cell response within the engineered hydrogel.

Made available in DSpace on 2021-06-25T11:55:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) National Council for Scientific and Technological Development Electrospun ultrathin fibrous scaffold filed with synthetic nanohydroxyapatite (nHAp) and graphene nanoribbons (GNR) has bioactive and osteoconductive properties and is a plausible strategy to improve bone regeneration. Poly(butylene-adipate-co-terephthalate) (PBAT) has been studied as fibrous scaffolds due to its low crystallinity, faster biodegradability, and good mechanical properties; however, its potential for in vivo applications remains underexplored. We proposed the application of electrospun PBAT with high contents of incorporated nHAp and nHAp/GNR nanoparticles as bone grafts. Ultrathin PBAT, PBAT/nHAp, and PBAT/nHAp/GNR fibers were produced using an electrospinning apparatus. The produced fibers were characterized morphologically and structurally using scanning electron (SEM) and high-resolution transmission electron (TEM) microscopies, respectively. Mechanical properties were analyzed using a texturometer. All scaffolds were implanted into critical tibia defects in rats and analyzed after two weeks using radiography, microcomputed tomography, histological, histomorphometric, and biomechanical analyses. The results showed through SEM and high-resolution TEM characterized the average diameters of the fibers (ranged from 0.208 mu m +/- 0.035 to 0.388 mu m +/- 0.087) and nHAp (crystallite around 0.28, 0.34, and 0.69 nm) and nHAp/GNR (200-300 nm) nanoparticles distribution into PBAT matrices. Ultrathin fibers were obtained, and the incorporated nHAp and nHAp/GNR nanoparticles were well distributed into PBAT matrices. The addition of nHAp and nHAp/GNR nanoparticles improved the elastic modulus of the ultrathin fibers compared to neat PBAT. High loads of nHAp/GNR (PBATnH5G group) improved the in vivo lamellar bone formation promoting greater radiographic density, trabecular number and stiffness in the defect area 2 weeks after implantation than control and PBAT groups. Sao Paulo State Univ, Inst Sci & Technol, Dept Biosci & Oral Diag, BR-12450000 Sao Paulo, Brazil Air Force Acad, Brazilian Air Force, BR-13630000 Pirassununga, Brazil UFPI Fed Univ Piaui, LIMAV Interdisciplinary Lab Adv Mat, BR-64049550 Teresina, Brazil Univ Brasil, Inst Cient & Tecnol, BR-12450000 Sao Paulo, Brazil Univ Fed Piaui, Dept Phys, BR-64049550 Teresina, Brazil Sao Paulo State Univ, Inst Sci & Technol, Dept Biosci & Oral Diag, BR-12450000 Sao Paulo, Brazil FAPESP: 2016/04618-7 National Council for Scientific and Technological Development: 310883/2020-2 National Council for Scientific and Technological Development: 404683/2018-AOL National Council for Scientific and Technological Development: 311531/2020-2

Ricardo Pereira Nogueira,1,2 Jose Deuzimar Uchoa,3,4 Fanny Hilario,2 Gabriela de Fátima Santana-Melo,5 Luana Marotta Reis de Vasconcellos,5 Fernanda Roberta Marciano,6 Virginie Roche,2 Alberto Moreira Jorge Junior,2,7 Anderson Oliveira Lobo4 1Chemical Engineering Department, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates; 2Université Grenoble Alpes, Université Savoie Mont Blanc, CNRS, GrenobleINP*LEPMI, Grenoble 38000, France; 3Federal Institute of Education, Science and Technology of Piauí, Teresina 64053-390, Brazil; 4Interdisciplinary Laboratory for Advanced Materials, BioMatLab Group, Materials Science and Engineering Graduate Program, UFPI – Federal University of Piaui, Teresina 64049-550 Brazil; 5Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, Sao Paulo State University, Sao José dos Campos 12245-000, Brazil; 6Department of Physics, Federal University of Piaui, Teresina PI 64049-550 Brazil; 7Department of Materials Engineering, Federal University of São Carlos, São Carlos 13565-905, BrazilCorrespondence: Anderson Oliveira LoboCampus Universitário Ministro Petrônio Portella, Av. Universitária, s/n, Centro de Tecnologia, Laboratório Interdisciplinar de Materiais Avançados, Ininga, Teresina, PI 64049-550, BrazilTel +55 86 32371057Email lobo@ufpi.edu.brBackground: Nanostructured surface modifications of Ti-based biomaterials are moving up from a highly-promising to a successfully-implemented approach to developing safe and reliable implants.Methods: The study’s main objective is to help consolidate the knowledge and identify the more suitable experimental strategies related to TiO2 nanotubes-modified surfaces. In this sense, it proposes the thorough investigation of two optimized nanotubes morphologies in terms of their biological activity (cell cytotoxicity, alkaline phosphatase activity, alizarin red mineralization test, and cellular adhesion) and their electrochemical behavior in simulated body fluid (SBF) electrolyte. Layers of small-short and large-long nanotubes were prepared and investigated in their amorphous and crystallized states and compared to non-anodized samples.Results: Results show that much more than the surface area development associated with the nanotubes’ growth; it is the heat treatment-induced change from amorphous to crystalline anatase-rutile structures that ensure enhanced biological activity coupled to high corrosion resistance.Conclusion: Compared to both non-anodized and amorphous nanotubes layers, the crystallized nano-structures’ outstanding bioactivity was related to the remarkable increase in their hydrophilic behavior, while the enhanced electrochemical stability was ascribed to the thickening of the dense rutile barrier layer at the Ti surface beneath the nanotubes.Keywords: surface modification, TiO2 nanotubes, commercially pure titanium, bioactivity

Background The role of combination chemotherapy has not yet been established in unresectable locally advanced pancreatic cancer (LAPC) lacking dedicated randomized trials. Methods This phase II trial tested the efficacy of Nab-paclitaxel (NAB-P)/Gemcitabine (G) versus G alone. Patients were randomized, 1:1 to G 1000 mg/m2 on days 1, 8 and 15 every 28 days versus NAB-P 125 mg/m2 on days 1, 8 and 15 every 28 days plus G 1000 mg/m2 on days 1, 8 and 15 every 28 days. Disease progression rate after three cycles of chemotherapy was the primary end-point. Progression-free survival (PFS), overall survival (OS) and response rate were secondary end-points. Findings A total of124 patients were enrolled. The study showed a reduction of a progressive disease from 45.6% with G to 25.4% with NAB-P/G (P = 0.01) at 3 months. Noteworthy, at 6 months in the G arm, 35.6% of patients present a metastatic spread versus 20.8% in the NAB/G arm. The response rate was 5.3% in the G arm and 27% in the NAB/G arm. Median PFS was 4 months for the G arm and 7 months for the NAB-P/G arm. Median OS was 10.6 in the G arm and 12.7 months in the NAB-P/G arm. One patient died during treatment with G due to a stroke. Interpretation. NAB-P/G reduced the rate of LAPC patients progressing after three cycles of chemotherapy compared with G, especially in terms of distant relapses. It positively affects PFS. To the best of our knowledge, this is the first randomized trial providing evidence that combination chemotherapy is superior to gemcitabine alone in this setting. ClinicalTrials.gov Identifier NCT02043730 .

Made available in DSpace on 2021-06-25T12:28:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-14 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The fibrous scaffolds for bone tissue engineering that mimic the extracellular matrix with bioactive and bactericidal properties could provide adequate conditions for regeneration of damaged bone. Electrospun ultrathin fiber covered with nano-hydroxyapatite is a favorable fibrous scaffold design. We developed a fast and reproducible strategy to produce polyvinylidene fluoride (PVDF)/nano-hydroxyapatite (nHAp) nanofibrous scaffolds with bactericidal and bioactive properties. Fibrous PVDF scaffolds were obtained first by the electrospinning method. Then, their surfaces were modified using oxygen plasma treatment followed by electrodeposition of nHAp. This process formed nanofibrous and superhydrophilic PVDF fibers (133.6 nm, fiber average diameter) covered with homogeneous nHAp (202.6 nm, average particle diameter) crystals. Energy-dispersive X-ray spectrometry demonstrated the presence of calcium phosphate, indicating a Ca/P molar ratio of approximately 1.64. X-ray diffraction, Fourier transform infrared spectroscopy, and Raman spectroscopy spectra identified beta-phase of nHAp. Thermal analysis indicated a slight reduction in stability after nHAp electrodeposition. Bactericidal assays showed that nHAp exhibited 99.8% efficiency against Pseudomonas aeruginosa bacteria. The PVDF/Plasma and PVDF/nHAp groups had the highest cell viability, total protein, and alkaline phosphatase activity by 7 days after exposure of the scaffolds to MG63 cell culture. Therefore, the developed scaffolds are an exciting alternative for application in bone regeneration. UFPI Fed Univ Piaui, Mat Sci & Engn Grad Program, BioMatLab Grp, LIMAV Interdisciplinary Lab Adv Mat, BR-64049550 Teresina, Piaui, Brazil Univ Brasil, Inst Cient & Tecnol, BR-08230030 Sao Paulo, Brazil UFPI Fed Univ Piaui, Dept Phys, 64049550 Teresina, PI, Brazil Univ UniMetrocamp, BR-13035500 Campinas, SP, Brazil Univ Estadual Campinas, Fac Med Sci, BR-13083970 Campinas, SP, Brazil Univ Santo Amaro, BR-04829300 Sao Paulo, Brazil Sao Paulo State Univ, Inst Sci & Technol, Dept Biosci & Oral Diag, BR-12247004 Sao Jose Dos Campos, SP, Brazil Sao Paulo State Univ, Inst Sci & Technol, Dept Biosci & Oral Diag, BR-12247004 Sao Jose Dos Campos, SP, Brazil CNPq: 303752/2017-3 CNPq: 404683/2018-5 CNPq: 304133/2017-5 CNPq: 424163/2016-0

Francilio Carvalho Oliveira,1,2,* Jancineide Oliveira Carvalho,1,2,* Suziete Batista Soares Gusmão,3 Licia de Sousa Gonçalves,2 Liana Martha Soares Mendes,4 Sérgio Antonio Pereira Freitas,2 Gustavo Oliveira de Meira Gusmão,5 Bartolomeu Cruz Viana,3,6 Fernanda Roberta Marciano,1,7,8 Anderson Oliveira Lobo1,3,8 1Institute of Science and Technology, Brasil University, Itaquera 08230-030, São Paulo, Brazil; 2University Center for Health, Humanities and Technology of Piauí, (UNINOVAFAPI), Teresina, Piauí, Brazil; 3LIMAV-Interdisciplinary Laboratory for Advanced Materials, Materials Science and Engineering Graduate Program, Technological Center, UFPI-Federal University of Piauí, Teresina 64049-550, Piaui, Brazil; 4Department of Specialized Medicine, Federal University of Piauí, Teresina 64017-775, Piaui, Brazil; 5Department of Physics, State University of Piaui, Teresina 64002-150, Piaui, Brazil; 6Department of Physics, Federal University of Piauí, Teresina 64049-550, Brazil; 7Nanomedicine Lab, Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 8Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA *These authors contributed equally to this work Background: It has been difficult to find bioactive compounds that can optimize bone repair therapy and adequate osseointegration for people with osteoporosis. The nano-hydroxyapatite (nHAp)/carbon nanotubes with graphene oxides, termed graphene nanoribbons (GNR) composites have emerged as promising materials/scaffolds for bone regeneration due to their bioactivity and osseointegration properties. Herein, we evaluated the action of nHAp/GNR composites (nHAp/GNR) to promote bone regeneration using an osteoporotic model.Materials and methods: First, three different nHAp/GNR (1, 2, and 3 wt% of GNR) were produced and characterized. For invivo analyses, 36 Wistar rats (var. albinus, weighing 250–300 g, Comissão de Ética no Uso de Animais [CEUA] n.002/17) were used. Prior to implantation, osteoporosis was induced by oophorectomy in female rats. After 45 days, a tibial fracture was inflicted using a 3.0-mm Quest trephine drill. Then, the animals were separated into six sample groups at two different time periods of 21 and 45 days. The lesions were filled with 3 mg of one of the above samples using a curette. After 21 or 45 days of implantation, the animals were euthanized for analysis. Histological, biochemical, and radiographic analyses (DIGORA method) were performed. The data were evaluated through ANOVA, Tukey test, and Kolmogorov-Smirnov test with statistical significance at P2% >1% wt.Conclusion: Therefore, it can be inferred that all analyzed nanoparticles promoted bone regeneration in osteoporotic rats independent of analyzed time. Keywords: biomaterials, invivo, osteoporosis, carbon nanotubes, graphene, nano-hydroxyapatite, composites

Background It has been difficult to find bioactive compounds that can optimize bone repair therapy and adequate osseointegration for people with osteoporosis. The nano-hydroxyapatite (nHAp)/carbon nanotubes with graphene oxides, termed graphene nanoribbons (GNR) composites have emerged as promising materials/scaffolds for bone regeneration due to their bioactivity and osseointegration properties. Herein, we evaluated the action of nHAp/GNR composites (nHAp/GNR) to promote bone regeneration using an osteoporotic model. Materials and methods First, three different nHAp/GNR (1, 2, and 3 wt% of GNR) were produced and characterized. For in vivo analyses, 36 Wistar rats (var. albinus, weighing 250-300 g, Comissao de Etica no Uso de Animais [CEUA] n.002/17) were used. Prior to implantation, osteoporosis was induced by oophorectomy in female rats. After 45 days, a tibial fracture was inflicted using a 3.0-mm Quest trephine drill. Then, the animals were separated into six sample groups at two different time periods of 21 and 45 days. The lesions were filled with 3 mg of one of the above samples using a curette. After 21 or 45 days of implantation, the animals were euthanized for analysis. Histological, biochemical, and radiographic analyses (DIGORA method) were performed. The data were evaluated through ANOVA, Tukey test, and Kolmogorov-Smirnov test with statistical significance at P Results Both nHAp and GNR exhibited osteoconductive activity. However, the nHAp/GNR exhibited regenerative activity proportional to their concentration, following the order of 3% >2% >1% wt. Conclusion Therefore, it can be inferred that all analyzed nanoparticles promoted bone regeneration in osteoporotic rats independent of analyzed time.

Made available in DSpace on 2020-12-12T02:25:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-20 Scientific and Technological Institute, Brasil University, São Paulo, SP, Brazil; Stady University of Maranhão, São Luís, MA, Brazil; Posgraduated Program in Medicine, Universidade Nove de Julho, UNINOVE, São Paulo, SP, Brazil; Department of Physics and Materials Science and Engineering graduate program, Federal University of Piaui, Teresina, PI, Brazil; Interdisciplinary Laboratory for Advanced Materials, Department of Materials Engineering, Federal University of Piaui, Teresina, PI, Brazil; Center for the Study of Venoms and Venomous Animals (CEVAP), UNESP, São Paulo State University, Botucatu, SP, Brazil; Center for the Study of Venoms and Venomous Animals (CEVAP), UNESP, São Paulo State University, Botucatu, SP, Brazil; Botucatu Medical School, UNESP, São Paulo State University, Botucatu, SP, Brazil; Stady University of Maranhão, São Luís, MA, Brazil

A method for the direct electrodeposition of globular nano-hydroxyapatite (nHAp) onto reduced graphene oxide (RGO) is presented and a model for the specific growth preference is discussed. Results show that the carboxyl (carboxylic acid)/carboxylate functional groups attached directly to the RGO after oxygen plasma treatment were essential to accelerate the OH– formation and the deposition of globular nHAp crystals. High resolution scanning electron microscopy, energy dispersive X-ray and X-ray diffraction showed that homogeneous, highly crystalline, stoichiometric nHAp crystals, with preferential growth in the (002) plane direction, were formed without any thermal treatment. The nHAp/RGO composites were shown to be an appropriate surface for mesenchymal stem cell adhesion with active formation of membrane projections.

We present a simple, low cost, and fast method to produce free-standing nanohydroxyapatite/carbon-based scaffolds. We electrodeposited nanohydroxyapatite onto vertically aligned carbon nanotube flakes and reticulated vitreous carbon bars. We prepared a highly crystalline and homogeneous thin film without any post-thermal treatment, and our results evidence that we can control the nanohydroxyapatite crystal formation according to the substrate employed. Immersion tests using simulated body fluid showed that these new nanobiomaterials had in vitro bioactivity. The free-standing nanohydroxyapatite/carbon-based scaffolds have been shown to be a suitable surface for mesenchymal stem cell adhesion with active formation of membrane projections and cell monolayer formation.

Stereolithography technology associated with the employment of photocrosslinkable, biocompatible, and bioactive hydrogels have been widely used. This method enables 3D microfabrication from images created by computer programs and allows researchers to design various complex models for tissue engineering applications. This study presents a simple and fast home-made stereolithography system developed to print layer-by-layer structures. Polyethylene glycol diacrylate (PEGDA) and gelatin methacryloyl (GelMA) hydrogels were employed as the photocrosslinkable polymers in various concentrations. Three-dimensional (3D) constructions were obtained by using the stereolithography technique assembled from a commercial projector, which emphasizes the low cost and efficiency of the technique. Lithium phenyl-2,4,6-trimethylbenzoyl phosphonate (LAP) was used as a photoinitiator, and a 404 nm laser source was used to promote the crosslinking. Three-dimensional and vascularized structures with more than 5 layers and resolutions between 42 and 83 µm were printed. The 3D printed complex structures highlight the potential of this low-cost stereolithography technique as a great tool in tissue engineering studies, as an alternative to bioprint miniaturized models, simulate vital and pathological functions, and even for analyzing the actions of drugs in the human body.