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Supramolecular hydrogels are of great interest in tissue scaffolding, diagnostics, and drug delivery due to their biocompatibility and stimuli-responsive properties. In particular, nucleosides are promising candidates as building blocks due to their manifold noncovalent interactions and ease of chemical modification. Significant progress in the field has been made over recent years to allow the use of nucleoside-based supramolecular hydrogels in the biomedical field, namely drug delivery and 3D bioprinting. For example, their long-term stability, printability, functionality, and bioactivity have been greatly improved by employing more than one gelator, incorporating different cations, including silver for antibacterial activity, or using additives such as boric acid or even biomolecules. This now permits their use as bioinks for 3D printing to produce cell-laden scaffolds with specified geometries and pore sizes as well as a homogeneous distribution of living cells and bioactive molecules. We have summarized the latest advances in nucleoside-based supramolecular hydrogels. Additionally, we discuss their synthesis, structural properties, and potential applications in tissue engineering and provide an outlook and future perspective on ongoing developments in the field.

© 2021 The Authors., Bacterial infection of implanted scaffolds may have fatal consequences and, in combination with the emergence of multidrug bacterial resistance, the development of advanced antibacterial biomaterials and constructs is of great interest. Since decades ago, metals and their ions had been used to minimize bacterial infection risk and, more recently, metal-based nanomaterials, with improved antimicrobial properties, have been advocated as a novel and tunable alternative. A comprehensive review is provided on how metal ions and ion nanoparticles have the potential to decrease or eliminate unwanted bacteria. Antibacterial mechanisms such as oxidative stress induction, ion release and disruption of biomolecules are currently well accepted. However, the exact antimicrobial mechanisms of the discussed metal compounds remain poorly understood. The combination of different metal ions and surface decorations of nanoparticles will lead to synergistic effects and improved microbial killing, and allow to mitigate potential side effects to the host. Starting with a general overview of antibacterial mechanisms, we subsequently focus on specific metal ions such as silver, zinc, copper, iron and gold, and outline their distinct modes of action. Finally, we discuss the use of these metal ions and nanoparticles in tissue engineering to prevent implant failure., M.G-G and U.E have received funding from the postdoctoral fellowship programme Beatriu de Pinós, funded by the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 programme of research and innovation of the European Union under the Marie Sklodowska-Curie grant agreement No 801370. R.A.P is supported by the Spanish Ministry by the Ramón y Cajal Program (RYC2018-025977-I). Additional financial support was provided by the Government of Catalonia (2017 SGR 708) and MINECO/FEDER project (RTI2018-096088-J-100).

Objectives:To identify the risk factors of neonatal sepsisduring the period from January 2017 to December 2019. Methods:A cross-sectional, retrospective study, observational, descriptive; the record of 106 newborns diagnosed with sepsis were reviewed. We excluded 15 were included in the data collection, diagnosis of early and late neonatal sepsis, maternal age, number of gestation, prenatal care, premature birth, diagnosis of UTI diagnosis of chorioamnionitis, premature rupture of membrane (s RPM ), sex product, invasive procedures, product weight and route of obtaining the product. Results:Of the 1401 patients obtained alive, 191 obtained diagnosis of neonatal sepsis and an incidence of 6.49% of early neonatal sepsis was obtained. The main risk factor associated with early neonatal sepsis has been the way of obtaining caesarean with 52.74%, the low birth weight with 32.96% and multiparity an incidence of 34.06% and there were no significant differences between sexes as the man / femalerelationship was 1.02.However if a significant importance in the delivery / caesarean relationship was obtained0.89. There was only one death recorded. Conclusions:The main risk factors associated with early neonatal sepsis are obtained via caesarean section, low birth weight and multiparity, male sex was the most affected but with no significant differences, the IVU, PROM, maternal age less to 18 years and the lack of prenatal care they had similar incidence. Only one late neonatal sepsis and death was obtained. I do not chorioamnionitis data was obtained.

The benign prostatic hyperplasia (BPH) is a (noncancerous) malignant growth in the size of the prostate. This enlargement of the prostate gland is produced by a relative increase in estrogen (female hormones) on testosterone (male hormone), which appears in men with age. Objective:To determine the relationship of PSA, with the size of the prostate in patients with benign prostatic hyperplasia admitted to General Hospital of Escarcega, Campeche Dr. Janel Aguilar during the period from August 2019 to January 2020. Method:patients were studied with the diagnosis of benign prostatic hyperplasia 50 years of age and older and excluded those who had other diseases that may alter prostate specific antigen, subsequently classified by age determined through PSA ultrasound prostate-specific and the average size of the prostate in grams and the average PSA for each age range and the relationship between them, while describes how it affects their self-esteem was determined. Results:Of the patients studied, 22 belong to the range of 50 to 59 years old (51.16%), 14 to range from 60 to 69 years old (32.55%) and 7 to range from 70 to 79 years old ( 16.27%). 44.1% of patients presented a prostate of 50 grams, the 51.16% prostates 60 grams and 4.6% a prostate gland of 70 grams. The average size of the prostate in grams was 50 grams in the range 50 to 59 years old, 60 g in the range 60 to 69 years old and 60 grams in the range of 70 to 79 years, and the average value of PSA was 5.5 ng / ml, 6 ng / ml and 7.5 ng / ml respectively. In the range 50 to 59 years of age every gram prostate equivalent to 0.11 ng / ml of PSA in the range 60 to 69 years of age every gram prostate equivalent to 0.1 ng / ml of PSA and the range 70 to 79 years old every gram of prostate equivalent to 0.125 ng / ml of PSA. Similarly we find that the entire population 72% have low self-esteem and problems with its image. Conclusions:In our environment in the group of 50-59 years old is the highest number of patients with benign prostatic hyperplasia.

BACKGROUND: The delivery of growth factors using a carrier system presents a promising and innovative tool in tissue engineering and dentistry today. Two of the foremost bioactive factors, bone morphogenetic protein-2 and vascular endothelial growth factor (VEGF), are widely applied using a ceramic scaffold. The aim of this study was to determine the use of hydroxyapatite microcarrier (MC) for dual delivery of osteogenic and angiogenic factors to accelerate hard tissue regeneration during the regenerative process. METHODS: Two MCs of different sizes were fabricated by emulsification of gelatin and alpha-tricalcium phosphate (α-TCP). The experimental group was divided based on the combination of MC size and growth factors. For investigating the in vitro properties, rat mesenchymal stem cells (rMSCs) were harvested from bone marrow of the femur and tibia. For in vivo experiments, MC with/without growth factors was applied into the standardized, 5-mm diameter defects, which were made bilaterally on the parietal bone of the rat. The animals were allowed to heal for 8 weeks, and samples were harvested and analyzed by micro-computed tomography and histology. RESULTS: Improved proliferation of rat mesenchymal stem cells was observed with VEGF loaded MC. For osteogenic differentiation, dual growth factors delivered by MC showed higher osteogenic gene expression, alkaline phosphatse production and calcium deposition. The in vivo results revealed statistically significant increase in new bone formation when dual growth factors were delivered by MC. Dual growth factors administered on a calcium phosphate matrix showed significantly enhanced osteogenic potential. CONCLUSION: We propose this system has potential clinical utility in providing solutions for craniofacial bone defects, with the added benefit of early availability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13770-020-00257-5) contains supplementary material, which is available to authorized users.

Corneal endothelium defects are one of the leading causes of blindness worldwide. The actual treatment is transplantation, which requires the use of human cadaveric donors, but it faces several problems, such as global shortage of donors. Therefore, new alternatives are being developed and, among them, cell therapy has gained interest in the last years due to its promising results in tissue regeneration. Nevertheless, the direct administration of cells may sometimes have limited success due to the immune response, hence requiring the combination with extracellular mimicking materials. In this review, we present different methods to obtain corneal endothelial cells from diverse cell sources such as pluripotent or multipotent stem cells. Moreover, we discuss different substrates in order to allow a correct implantation as a cell sheet and to promote an enhanced cell behavior. For this reason, natural or synthetic matrixes that mimic the native environment have been developed. These matrixes have been optimized in terms of their physicochemical properties, such as stiffness, topography, composition and transparency. To further enhance the matrixes properties, these can be tuned by incorporating certain molecules that can be delivered in a sustained manner in order to enhance biological behavior. Finally, we elucidate future directions for corneal endothelial regeneration, such as 3D printing, in order to obtain patient-specific substrates.

Bone grafting is one of the most commonly performed treatments for bone healing or repair. Autografts, grafts from the same patient, are the most frequently used bone grafts because they can provide osteogenic cells and growth factors at the site of the implant with reduced risk of rejection or transfer of diseases. Nevertheless, this type of graft presents some drawbacks, such as pain, risk of infection, and limited availability. For this reason, synthetic bone grafts are among the main proposals in regenerative medicine. This branch of medicine is based on the development of new biomaterials with the goal of increasing bone healing capacity and, more specifically in dentistry, they aim at simultaneously preventing or eliminating bacterial infections. The use of fibers made of chitosan (CS) and hydroxyapatite (HA) loaded with an antibiotic (doxycycline, DX) and fabricated with the help of an injection pump is presented as a new strategy for improving maxillary bone regeneration. In vitro characterization of the DX controlled released from the fibers was quantified after mixing different amounts of HA (10–75%). The 1% CS concentration was stable, easy to manipulate and exhibited adequate cuttability and pH parameters. The hydroxyapatite concentration dictated the combined fast and controlled release profile of CSHA50DX. Our findings demonstrate that the CS-HA-DX complex may be a promising candidate graft material for enhancing bone tissue regeneration in dental clinical practice. info:eu-repo/semantics/publishedVersion

The use of copper (Cu2+) and cobalt (Co2+) has been described to stimulate blood vessel formation, a key process for the success of tissue regeneration. However, understanding how different concentrations of these ions affect cellular response is important to design scaffolds for their delivery to better fine tune the angiogenic response. On the one hand, gene expression analysis and the assessment of tubular formation structures with human umbilical vein endothelial cells (HUVEC) revealed that high concentrations (10μM) of Cu2+in early times and lower concentrations (0.1 and 1μM) at later times (day 7) enhanced angiogenic response. On the other hand, higher concentrations (25μM) of Co2+during all time course increased the angiogenic gene expression and 0.5, 5 and 25μM enhanced the ability to form tubular structures. To further explore synergistic effects combining both ions, the non-toxic concentrations were used simultaneously, although results showed an increased cell toxicity and no improvement of angiogenic response. These results provide useful information for the design of Cu2+or Co2+delivery scaffolds in order to release the appropriate concentration during time course for blood vessel stimulation.

Barrier membranes are essential biomaterials for guided bone regeneration. Due to different origin and structure of barrier membranes, singular mechanical properties and clinical behaviors can be expected. It is important to understand the physic and chemical properties of barrier membranes to select the needed biomaterial for each clinical situation. To date, no study has evaluated and compared the physicochemical properties of various families of barrier membranes. The aim of this study is to evaluate the physicochemical properties of various barrier membranes. Fifteen membranes of different origin were tested in this study. Membranes were divided into biological or synthetic origin and grouped in natural allogenic collagen, natural xenogenic collagen, cross-linked collagen and synthetic membranes. Physicochemical properties were evaluated in terms of tension, stiffness, absorption ability, pH and wettability. For the tension tests, all membranes showed similar low tension and low stiffness, especially after a 4-min hydration, except for bone laminas that showed a greater stiffness particularly in a dry status. Regarding wettability and hydration of the barrier membranes, porcine origin membranes had greater hydration; wettability was also superior in porcine derived barrier membranes and showed a faster absorption of the drop on the rough surfaces. All membranes had a stable pH, having the synthetic membranes the most stable pH when compared to physiologic. The wide variety of barrier membranes opens a debate in which the practitioner should select the adequate barrier membrane for each clinical situation. Different materials show singular potentials depending on their tissue origin making them suitable for specific clinical indications. More studies regarding adsorption, integration and degradation of barrier membranes are needed to understand their behavior.

Cardiovascular disease (CVD) is the leading cause of death among persons aged 65 and older in the United States and many other developed countries. Tissue engineered vascular systems (TEVS) can serve as grafts for CVD treatment and be used as in vitro model systems to examine the role of various genetic factors during the CVD progressions. Current focus in the field is to fabricate TEVS that more closely resembles the mechanical properties and extracellular matrix environment of native vessels, which depends heavily on the advance in biofabrication techniques and discovery of novel biomaterials. In this review, we outline the mechanical and biological design requirements of TEVS and explore the history and recent advances in biofabrication methods and biomaterials for tissue engineered blood vessels and microvascular systems with special focus on in vitro applications. In vitro applications of TEVS for disease modeling are discussed. info:eu-repo/semantics/publishedVersion

The benign prostatic hyperplasia (BPH)is a (noncancerous) malignant growth in the size of the prostate. This enlargement of the prostate gland is produced by a relative increase in estrogen (female hormones) on testosterone (male hormone), which appears in men with age. Objective:To determine the relationship of PSA, with the size of the prostate in patients with benign prostatic hyperplasia admitted to General Hospital of Escarcega, Campeche Dr. Janel Aguilar during the period from August 2019 to January 2020. Method:patients were studied with the diagnosis of benign prostatic hyperplasia 50 years of age and older and excluded those who had other diseases that may alter prostate specific antigen, subsequently classified by age determined through PSA ultrasound prostate-specific and the average size of the prostate in grams and the average PSA for each age range and the relationship between them, while describes how it affects their self-esteem was determined. Results:Of the patients studied, 22 belong to the range of 50 to 59 years old (51.16%), 14 to range from 60 to 69 years old (32.55%) and 7 to range from 70 to 79 years old ( 16.27%). 44.1% of patients presented a prostate of 50 grams, the 51.16% prostates 60 grams and 4.6% a prostate gland of 70 grams. The average size of the prostate in grams was 50 grams in the range 50 to 59 years old, 60 g in the range 60 to 69 years old and 60 grams in the range of 70 to 79 years, and the average value of PSA was 5.5 ng / ml, 6 ng / ml and 7.5 ng / ml respectively. In the range 50 to 59 years of age every gram prostate equivalent to 0.11 ng / ml of PSA in the range 60 to 69 years of age every gram prostate equivalent to 0.1 ng / ml of PSA and the range 70 to 79 years old every gram of prostate equivalent to 0.125 ng / ml of PSA. Similarly we find that the entire population 72% have low self-esteem and problems with its image. Conclusions:In our environment in the group of 50-59 years old is the highest number of patients with benign prostatic hyperplasia.&nbsp

Ion release from dental implants and prosthetic restoration can affect osteointegration and implant viability over a long period of time. Therefore, the aim of this study was to study the ion release from implants and crowns, with and without intermediate anodized abutments, in two different media, simulating clinical conditions. The implants, intermediate prosthetic abutments and Cr&ndash, Co crowns were divided into two groups depending on the media: Hanks&rsquo, solution and 1% lactic acid, simulating body fluids and microbiologically conditioned fluids, respectively. The study followed the ISO 10271:2011 and 10993-15:2000 standards modified to simulate the replacement of fluids in the oral environment. The ions&rsquo, release was measured by inductively coupled plasma mass spectroscopy (ICP-EOS), and only aluminum, chromium, cobalt, titanium and vanadium were identified. Ion concentration was higher in lactic acid than in Hanks&rsquo, solution at all time points (p &lt, 0.05). Only vanadium showed a very low ion release in lactic acid, with no statistically significant differences from the ion release in Hanks&rsquo, solution (p = 0.524). Both anodized abutments and the immersion medium influenced the release of ions and affected the corrosion of these structures. The presence of an intermediate anodized abutment also affected ion release, as the level of ions was lower in groups with this component.

Objectives:To identify the risk factors of neonatal sepsisduring the period from January 2017 to December 2019. Methods:A cross-sectional, retrospective study, observational, descriptive; the record of 106 newborns diagnosed with sepsis were reviewed. We excluded 15 were included in the data collection, diagnosis of early and late neonatal sepsis, maternal age, number of gestation, prenatal care, premature birth, diagnosis of UTI diagnosis of chorioamnionitis, premature rupture of membrane (s RPM ), sex product, invasive procedures, product weight and route of obtaining the product. Results:Of the 1401 patients obtained alive, 191 obtained diagnosis of neonatal sepsis and an incidence of 6.49% of early neonatal sepsis was obtained. The main risk factor associated with early neonatal sepsis has been the way of obtaining caesarean with 52.74%, the low birth weight with 32.96% and multiparity an incidence of 34.06% and there were no significant differences between sexes as the man / femalerelationship was 1.02.However if a significant importance in the delivery / caesarean relationship was obtained0.89. There was only one death recorded. Conclusions:The main risk factors associated with early neonatal sepsis are obtained via caesarean section, low birth weight and multiparity, male sex was the most affected but with no significant differences, the IVU, PROM, maternal age less to 18 years and the lack of prenatal care they had similar incidence. Only one late neonatal sepsis and death was obtained. I do not chorioamnionitis data was obtained.

Bone is the most studied tissue in the field of tissue regeneration. Even though it has intrinsic capability to regenerate upon injury, several pathologies and injuries could hamper the highly orchestrated bone formation and resorption process. Bone tissue engineering seeks to mimic the extracellular matrix of the tissue and the different biochemical pathways that lead to successful regeneration. For many years, the use of extrinsic factors (i.e., growth factors and drugs) to modulate these biological processes have been the preferred choice in the field. Even though it has been successful in some instances, this approach presents several drawbacks, such as safety-concerns, short release profile and half-time life of the compounds. On the other hand, the use of inorganic ions has attracted significant attention due to their therapeutic effects, stability and lower biological risks. Biomaterials play a key role in such strategies where they serve as a substrate for the incorporation and release of the ions. In this review, the methodologies used to incorporate ions in biomaterials is presented, highlighting the osteogenic properties of such ions and the roles of biomaterials in controlling their release. info:eu-repo/semantics/publishedVersion

Background Failure of the corneal endothelium cell (CEC) monolayer is the main cause leading to corneal transplantation. Autologous cell-based therapies are required to reconstruct in vitro the cell monolayer. For this purpose, we propose the use of dental pulp stem cells isolated from the third molars to form CEC monolayer. We hypothesize that by using dental pulp stem cells (DPSC) that share an embryological origin with CEC, as they both arise from the neural crest, may allow a direct differentiation process avoiding the use of reprogramming techniques, such as induced pluripotent stem cells (iPSC). Methods In this work, we report a two-step differentiation protocol, where dental pulp stem cells are derived into neural crest stem cells and, then, into CEC. Results Initially, we compared the efficiency of direct differentiation of DPSC with the differentiation of iPSC to express NCSC related genes in adhesion culture, showing significantly higher levels of early stage marker AP2 for the DPSC compared to iPSC. To provide better environment for NCSC gene expression, suspension method was performed, which induced the formation of neurospheres. The results showed neurosphere formation after few days, obtaining the peak of NCSC marker expression after 4 days, showing overexpression of AP2, p75 and CHD7 markers, confirming the formation of NCSC like cells. Furthermore, pluripotent markers Oct4, Nanog and Sox2 were as well upregulated in suspension culture. Neurospheres were then directly cultured in CEC conditioned medium for the second differentiation, showing the conversion of DPSC into polygonal like cells expressing higher levels of ZO-1, ATP1A1, COL4A2 and COL8A1 markers, providing proof of the successful conversion into CEC. Conclusions Therefore, our findings demonstrate that patient-derived dental pulp stem cells represent an autologous cell source for corneal endothelial regeneration that avoids actual transplantation limitations as well as reprogramming techniques.

In this communication we report that anchoring avß3 or a5ß1 integrin-selective RGD peptidomimetics to titanium efficiently tunes mesenchymal stem cell response in vitro and bone growth in rat calvarial defects. Our results demonstrate that this molecular chemistry-derived approach could be successful to engineer instructive coatings for orthopedic applications.

Promoting angiogenesis is a key strategy for stimulating the repair of damaged tissues, including bone. Among other proangiogenic factors, ions have recently been considered a potent element that can be incorporated into biomaterials and then released at therapeutic doses. Silicate-based biomaterials have been reported to induce neovascularization through vascular endothelial growth factor signaling pathway, potentiating acceleration of bone regeneration. Here, we designed a silicate-shelled hydrogel fiber scaffold with a hard/soft layered structure to investigate the possibility of silicate coating on biopolymer for enhancing biological properties. An alginate hydrogel was injected to form a fiber scaffold with shape-tunability that was then coated with a thin silicate layer with various sol-gel compositions. The silicate/alginate scaffold could release calcium and silicate ions, and in particular, silicate ion release was highly sustainable for over one week at therapeutically relevant levels. The ionic release was highly effective in stimulating the mRNA expression of angiogenic markers (VEGF, KDR, eNOS, bFGF, and HIF1-α) in endothelial cells (HUVECs). Moreover, the in vitro tubular networking of cells was significantly enhanced (1.5 times). In vivo implantation in subcutaneous tissue revealed more pronounced blood vessel formation around the silicate-shelled scaffolds than around silicate-free scaffolds. The presence of a silicate shell was also shown to accelerate acellular mineral (hydroxyapatite) formation. The cellular osteogenesis potential of the silicate/alginate scaffold was further proven by the enhanced expression of osteogenic genes (Col1a1, ALP and OCN). When implanted in a rat calvarium defect, the silicate-shelled scaffold demonstrated significantly improved bone formation (2-3 times higher in bone volume and density) with a concurrent sign of proangiogenesis. This work highlights that the surface-layering of silicate composition is an effective approach for improving the bone regeneration capacity of polymeric hydrogel scaffolds by stimulating ion-induced angiogenesis and providing bone bioactivity to the surface.

Injectable calcium phosphate cements (CPCs) with strong mechanical properties and improved biological performance have the potential to be extensively used for bone regeneration. Although many additive materials have been incorporated into CPCs in order to achieve improvements in their mechanical and biological properties, somehow the results have not been fully satisfactory. Here we focus on using the nanoparticle form of mesoporous bioactive glasses (mBGn) as additive nano-components for alpha-tricalcium phosphate-based CPCs. The effects of mBGn incorporated up to 10 wt% into CPCs were examined in depth with respect to the setting time, morphology, injectability, wash-out properties, consistency, ionic release, pH change, and mechanical strength. The addition of mBGn significantly increased the surface area (for both the as-cemented and the hydrated compositions) and also significantly accelerated the setting reaction of CPCs. The injectability and the anti-washout property of CPCs were remarkably enhanced with the addition of mBGn. In striking contrast to the case of pure CPCs, the morphological changes observed in simulated body fluid (SBF) revealed a spherical development of apatite crystals, replicating the nanospherical morphology of the mBGn and consequently resulting in a nano-micro-roughened surface. The mechanical compressive strength substantially increased after SBF immersion and significantly higher values were recorded for mBGn/CPC as compared to pure CPCs. The ion release, including that of calcium, phosphate, and silicon, was recorded at substantial levels during the test period, and the addition of mBGn caused changes in the pH towards less acidic. The in vivo study of the mBGn/CPCs in rat subcutaneous tissue confirmed excellent tissue compatibility with little evidence of inflammatory reactions while exhibiting viable fibroblastic cells with a substantial presence of mature endothelial cells surrounding the cements. When implanted in a rat calvarium defect, a substantial degradation of the samples was noticed in the interfacial region. The proposed mBGn/CPC is a novel, promising cement formulation for the repair and regeneration of bone due to setting characteristics, physico-chemical and mechanical properties, and excellent in vivo tissue compatibility and bioactivity.

This paper investigates the optimized sputtering conditions for high quality gallium oxide (Ga2O3) thin films while maintaining a strong uniformity within a specific surface area. The research also analyzes the crystal structure and the morphology of gallium oxide (Ga2O3) thin films. We report a comprehensive investigation of two different types of Ga2O3 synthetization processes: (1) direct deposition using radio frequency (RF) magnetron sputter technique and (2) thermal oxidation of gallium nitride (GaN) samples. A detailed comparison is presented in terms of material characterization, surface analysis and electrical performance for each of the synthetization processes. X-ray photoelectron spectroscopy, scanning electron microscopy, atomic force microscopy and x-ray diffraction (XRD) are employed to study the gallium oxide (Ga2O3) epi-layers on each of the samples. Based on the analysis, Ga2O3 compound is found on all samples with a binding energy ranging from 21 eV to 21.38 eV. Depending on the synthetization process, the thickness varied from 20 nm to 100 nm for RF sputtering process and a maximum of ~ 400 nm for thermal oxidation method. Additionally, the observations revealed that Ga2O3 is formed on the surface, as well as inside the gallium nitride (GaN) film after thermal oxidation. Crystal features are observed on the surface of each of the samples after annealing treatment while XRD analysis showed the presence of the beta (β) polymorph for the annealed samples. After thorough characterization, radio frequency sputtering technique proved to be superior due to its higher purity level and ability to create polycrystalline structures by adding temperature during deposition.

Biomedical cements are considered promising injectable materials for bone repair and regeneration . Calcium phosphate composition sized with tens of micrometers is currently one of the major powder forms. Here we report a unique cement form made from mesoporous bioactive glass nanoparticles (BGn). The nanopowder could harden in reaction with aqueous solution at powder-to-liquid ratios as low as 0.4–0.5 ( vs . 2.0–3.0 for conventional calcium phosphate cement CPC). The cementation mechanism investigated from TEM, XRD, FT-IR, XPS, and NMR analyses was demonstrated to be the ionic (Si and Ca) dissolution and then reprecipitation to form Si-Ca-(P) based amorphous nano-islands that could network the particles. The nanopowder-derived nanocement exhibited high surface area (78.7 m 2 /g); approximately 9 times higher than conventional CPC. The immersion of nanocement in simulated body fluid produced apatite nanocrystallites with ultrafine size of 10 nm ( vs. 55 nm in CPC). The ultrafine nanocement adsorbed protein molecules (particularly positive charged proteins) at substantial levels; approximately 160 times higher than CPC. The nanocement released Si and Ca ions continuously over the test period of 2 weeks; the Si release was unique in nanocement whereas the Ca release was in a similar range to that observed in CPC. The release of ions significantly stimulated the responses of cells studied (rMSCs and HUVECs). The viability and osteogenesis of rMSCs were significantly enhanced by the nanocement ionic extracts. Furthermore, the in vitro tubular networking of HUVECs was improved by the nanocement ionic extracts. The in vivo neo-blood vessel formation in CAM model was significantly higher by the nanocement implant when compared with the CPC counterpart, implying the Si ion release might play a significant role in pro-angiogenesis. Furthermore, the early bone forming response of the nanocement, based on the implantation in a rat calvarial bone defect, demonstrated a sign of osteoinductivity along with excellent osteocondution and bone matrix formation. Although more studies remain to confirm the potential of nanocement, some of the intriguing physico-chemical properties and the biological responses reported herein support the promise of the new ‘nanopowder-based nanocement’ for hard tissue repair and regeneration .

The objective of this study was to assess, by histomorphometric analysis, the degree of bone apposition on two types of dental implant’s surfaces: a novel implant that combines Al2O3 abrasive particle blasting with thermochemical treatment (ContacTi), compared to a standard surface treatment obtained by sandblasting and acid etching (shot blasting). Twelve minipigs were used, placing the studied implants in the maxillae, and divided into three groups according to the time of sacrifice: 2, 4, and 8 weeks after implant placement. Histological and histomorphometric analyses were performed following standardized tissue polymerization, cutting, and staining and examined under optical and high-resolution electron microscope. For all measurements, the novel surface presented higher levels of osseointegration as compared to the shot blasting surface. Bone to implant contact (BIC) in the maxillae for ContacTi presented values of 49.02, 83.20, and 85.58% at 2, 4, and 8 weeks, respectively, significantly higher compared to the shot blasting surface values of 39.32, 46.53, and 46.20% for the same time points. Bone area density (BAD) presented values of 26.52, 61.21, and 59.50% for ContacTi surface implants and 22.95, 36.26, and 49.50% for the shot blasted surface implants. Signs of osteoconductivity were observed in the ContacTi surfaces at 2 weeks. The ContacTi surface achieved a faster growth of hard tissues around the implants, when compared to the shot blasting surface, and for all evaluated histomorphometric parameters, the values were higher at all measured time points. ContacTi could be a new surface improving the osseointegration in oral implantology.

Background:The topographical features on the surface of dental implants have been considered as a critical parameter for enhancing the osseointegration of implants. In this work, we proposed a surface obtained by a combination of shot blasting and double acid etching. The double acid etching was hypothesized to increase the submicron topography and hence further stimulate the biological properties of the titanium implant.Methods:The topographical features (surface roughness and real surface area), wettability and surface chemical composition were analyzed.Results:The results showed that the proposed method produced a dual roughness, mainly composed of randomly distributed peaks and valleys with a superimposed nanoroughness, and hence with an increased specific surface area. Despite the fact that the proposed method does not introduce significant chemical changes, this treatment combination slightly increased the amount of titanium available on the surface, reducing potential surface contaminants. Furthermore, the surface showed increased contact angle values demonstrating an enhanced hydrophobicity on the surface. The biological behavior of the implants was then assessed by culturing osteoblast-like cells on the surface, showing enhanced osteoblast adhesion, proliferation and differentiation on the novel surface.Conclusions:Based on these results, the described surface with dual roughness obtained by double acid etching may be a novel route to obtain key features on the surface to enhance the osseointegration of the implant. Our approach is a simple method to obtain a dual roughness that mimics the bone structure modified by osteoclasts and increases surface area, which enhances osseointegration of dental implants.

The use of narrow titanium dental implants (NDI) for small ridges, reduced interdental space, or missing lateral incisors can be a viable option when compared to the conventional wider dental implants. Furthermore, in many cases, standard diameter implant placement may not be possible without grafting procedures, which increases the healing time, cost, and morbidity. The aim of this study was to analyze the mechanical viability of the current narrow implants and how narrow implants can be improved. Different commercially available implants (n = 150) were tested to determine maximum strength, strain to fracture, microhardness, residual stress, and fatigue obtaining the stress&ndash, number of cycles to fracture (SN) curve. Fractography was studied by scanning electron microscopy. The results showed that when the titanium was hardened by the addition of 15% of Zr or 12% cold worked, the fatigue limit was higher than the commercially pure grade 4 Ti without hardening treatment. Grade 4 titanium without hardening treatment in narrow dental implants can present fractures by fatigue. These narrow implants are subjected to high mechanical stresses and the mechanical properties of titanium do not meet the minimal requirements, which lead to frequent fractures. New hardening treatments allow for the mechanical limitations of conventional narrow implants to be overcome in dynamic conditions. These hardening treatments allow for the design of narrow dental implants with enhanced fatigue life and long-term behavior.

Although ceramic-on-ceramic (CoC) bearings have been shown to produce the smallest amount of wear volume in vitro as well as in vivo studies when used for total hip arthroplasties (THA), concerns about the failure of these bearing surfaces persist due to early failures observed after short postoperative time. In this study, an exhaustive analysis of the early failure occurred on the new generation of ceramic bearings, consisting of a composite alumina matrix-based material reinforced with yttria-stabilized tetragonal zirconia (Y-TZP) particles, chromium dioxide, and strontium crystals, was performed. For this study, 118 CoC bearings from 117 patients were revised. This article describes a group of mechanical failure CoC-bearing BIOLOX THA hip prosthesis patients without trauma history. The retrieved samples were observed under scanning electron microscopy (SEM), composition was analyzed with energy dispersive X-ray spectroscopy (EDX), and damaged surfaces were analyzed by grazing-incidence X-ray diffraction (GI-XRD) and white light interferometry. In the short term, CoC articulations provided similar mechanical behavior and functional outcome to those in XLPE cases. However, 5% more early mechanical failures cases were observed for the ceramic components. Although the fracture rate of third generation CoC couples is low, the present study shows the need to further improve the third generation of CoC-bearing couples for THA. Despite the improved wear compared to other materials, stress concentrators are sources of initial crack propagation, such as those found in the bore-trunnion areas. Moreover, in view of the evidence observed in this study, the chipping observed was due to the presence of monoclinic phase of the Y-TZP instead of tetragonal, which presents better mechanical properties. The results showed that total safety after receiving a THA is still a goal to be pursued. info:eu-repo/semantics/publishedVersion

The aim of this study was to evaluate the biomechanical behavior of Bone Level dental implants with four different neck designs in contact with cortical bone. Numerical simulations were performed using a Finite Element Method (FEM) based-model. In order to verify the FEM model, the in silico results were compared with the results obtained from histological analysis performed in an in vivo study with New Zealand rabbits. FEM was performed using a computerized 3D model of Bone Level dental implants inserted in the lower jaw bone with an applied axial load of 100 N. The analysis was performed using four different implant neck designs: even surfaced, screwed, three-ring design and four-ring design. Interface are of bone growth was evaluated by analyzing the Bone-Implant-Contact (BIC) parameter obtained from in vivo histological process and analyzed by Scanning Electron Microscopy (SEM). Bone Level implants were inserted in the rabbit tibia, placing two implants per tibia. The BIC was evaluated after three and six weeks of implantation. FEM studies showed that the three-ring design presented lower values of stress distribution compared to the other studied designs. The lower levels of mechanical stress were then correlated with the in vivo studies, showing that the three-ring design presented the highest BIC value after 3 and 6 weeks of implantation. In silico and in vivo results both concluded that the implants with three-ring neck design presented the best biomechanical and histological behavior in terms of new bone formation, enhanced mechanical stability and optimum osseointegration.

The surface modifications of titanium dental implants play important roles in the enhancement of osseointegration. The objective of the present study was to test two different implant surface treatments on a rabbit model to investigate the osseointegration. The tested surfaces were: a) acid-etched surface with sandblasting treatment (SA) and b) an oxidized implant surface (OS). The roughness was measured by an interferometeric microscope with white light and the residual stress of the surfaces was measured with X-ray residual stress Bragg–Bentano diffraction. Six New Zealand white rabbits were used for the in vivo study. Implants with the two different surfaces (SA and OS) were inserted in the femoral bone. After 12 weeks of implantation, histological and histomorphometric analyses of the blocks containing the implants and the surrounding bone were performed. All the implants were correctly implanted and no signs of infection were observed. SA and OS surfaces were both surrounded by newly formed trabeculae. Histomorphometric analysis revealed that the bone–implant contact % (BIC) was higher around the SA implants (53.49 ± 8.46) than around the OS implants (50.94 ± 16.42), although there were no significant statistical differences among them. Both implant surfaces (SA and OS) demonstrated a good bone response with significant amounts of newly formed bone along the implant surface after 12 weeks of implantation. These results confirmed the importance of the topography and physico–chemical properties of dental implants in the osseointegration. The authors are grateful to the Spanish Government and European Union FEDER by the concession of the project RTI2018-098075-B-C22 SI

Angiogenic capacity of biomaterials is a key asset to drive vascular ingrowth during tissue repair and regeneration. Here we design a unique angiogenic microcarrier based on sol-gel derived mesoporous silica. The microspheres offer a potential angiogenic stimulator, Si ion, 'intrinsically' within the chemical structure. Furthermore, the highly mesoporous nature allows the loading and release of angiogenic growth factor 'extrinsically'. The Si ion is released from the microcarriers at therapeutic ranges (over a few ppm per day), which indeed up-regulates the expression of hypoxia inducing factor 1α (HIF1α) and stabilizes it by blocking HIF-prolyl hydroxylase 2 (PHD2) in HUVECs. This in turn activates the expression of a series of proangiogenic molecules, including bFGF, VEGF, and eNOS. VEGF is incorporated effectively within the mesopores of microcarriers and is then released continuously over a couple of weeks. The Si ion and VEGF released from the microcarriers synergistically stimulate endothelial cell functions, such as cell migration, chemotactic homing, and tubular networking. Furthermore, in vivo neo-blood vessel sprouting in chicken chorioallantoic membrane model is significantly promoted by the Si/VEGF releasing microcarriers. The current study demonstrates the synergized effects of Si ion and angiogenic growth factor through a biocompatible mesoporous microsphere delivery platform, and the concept provided here may open the door to a new co-delivery system of utilizing ions with growth factors for tissue repair and regeneration.

Silica-based nanomaterials (SiNMs) with different forms, including nanoparticles, nanorods and nanofibers either with a dense, porous or hollow structure, have been demonstrated as fascinating platforms for the delivery of therapeutic molecules in the inorganic nanocarrier regime. This is primarily due to their unique physicochemical properties, which are effective and tunable for the uptake of different cargo molecules, as well as to their biological responses favorable for cells and tissues. Over the last decade, a substantial number of studies have exploited SiNMs with different shapes, sizes, mesopore structures and surface charges for use in cancer therapy, imaging and bioseparation. In particular, their surface can be functionalized with candidate molecules from dyes to drugs for theranostic purposes. Moreover, providing the carriers with intelligent modes, such as stimuli-responsiveness, and with multifunctionality through combining them with imaging particles (magnetic nanoparticles, quantum dots and carbon dots) improves their therapeutic and diagnostic potential. While many pioneering works in the SiNM systems have focused on cancer therapy, there is growing demand for using SiNMs in the area of regenerative medicine, for stem cell therapy and tracking, and for the repair of dysfunctional tissues. Here we review the most recent advances in SiMNs that are available for regenerative therapies. For this, we first give an overview of the general nanostructure forms and characteristics of the SiNMs from a physicochemical and biological point of view, and then deal with the intracellular uptake mechanism and toxicity issues. Finally, advanced designs of SiNMs to provide multifunctional and intelligent actions of loading and delivery of drugs and molecules are detailed, and then perspectives for their potential uses in regenerative medicine are provided.

Providing an osteogenic stimulatory environment is a key strategy to construct stem cell-based bone-equivalent tissues. Here we design a stem cell delivering gel matrix made of collagen (Col) with bioactive glass nanocarriers (BGn) that incorporate osteogenic signaling molecule, fibroblast growth factor 18 (FGF18), a reservoir considered to cultivate and promote osteogenesis of mesenchymal stem cells (MSCs). The presence of BGn in the gel was shown to enhance the osteogenic differentiation of MSCs, possibly due to the therapeutic role of ions released. The mesoporous nature of BGn was effective in loading FGF18 at large quantity, and the FGF18 release from the BGn-Col gel matrix was highly sustainable with almost a zero-order kinetics, over 4 weeks as confirmed by the green fluorescence protein signal change. The released FGF18 was effective in accelerating osteogenesis (alkaline phosphatase activity and bone related gene expressions) and bone matrix formation (osteopontin, bone sialoprotein, and osteocalcin production) of MSCs. This was attributed to the bone morphogenetic protein (BMP) signaling pathway, where the FGF18 release stimulated the endogenous secretion of BMP2 and the downstream signal Smad1/5/8. Taken together, the FGF18-BGn/Col gel is considered an excellent osteopromoting depot to support and signal MSCs for bone tissue engineering.

Pluripotent stem cells (PSCs) derived from either the embryo or reprogramming processes have the capacity to self-renew and differentiate into various cells in the body, thereby offering a valuable cell source for regenerative therapy of intractable disease and serious tissue damage. Traditionally, methods to expand and differentiate PSCs have been confined to 2D culture through the use of biochemical signals; the use of biomaterials beyond the commercially available culture dish has not been widespread. Nevertheless, biomaterials with tailored physical, chemical, and geometrical cues can mimic the native stem cell niche to tune the microenvironmental conditions for PSCs to preserve their self-renewal capacity or to switch their phenotype, a status ultimately needed to gain regenerative functions ex vivo and in vivo. Recently efforts to explore biomaterials to regulate PSC behavior have accelerated. The biomaterials properties investigated include surface chemistry, immobilized ligand, nano-/micro-topography, matrix stiffness, geometrical complexity, 3D configuration, and combinations thereof. This review aims to cover the current advances of biomaterials-based control over PSCs, particularly for the preservation of self-renewal capacity as well as for their differentiation into target cells. Furthermore, it aims to suggest future research directions that would facilitate the eventual translation of these advances.

The application of 3D printed scaffolds for bone tissue regeneration has been explored in previous studies. In this study, we combined 3D printing with porogen leaching to develop scaffolds with dual-scale porosity and investigated their capability in guided bone regeneration in a rat critical size calvarial defect model. The scaffolds were additively manufactured from medical grade polycaprolactone (mPCL) doped with porogen microparticles having an average size of 22 μm, which were subsequently leached to create microscale porosity. Morphological analysis revealed an interconnected macroscale porosity of about 60% with an average pore size of 700 µm and intra-strut microscale pores with a porosity of nearly 40% and average pore size of 20–70 µm. The microscale porosity resulted in a 3-fold increase in the scaffolds’ surface area, a 2-fold enrichment in negatively charged surface groups, which did lead to significantly increased protein adsorption and faster hydrolysis-driven degradation in vitro. An in vitro blood clotting assay demonstrated an increased TGF-β1 release from the clots formed on the dual-scale porous scaffolds. In a rat calvarial defect, bone formation was found in both the macro- and microscale pores and was at a similar level when compared to calcium phosphate coated mPCL scaffolds.

this paper is based upon work from COST Action ICSHNet. To develop and apply recently proposed methods for assessing the health impact of pollution from contaminated sites and apply them to the case of landfills using available large European datasets.standard methods for health impact assessment and burden of disease were applied using the available evidence on the health effects of living near a landfill. Geo-referenced data on landfills from the European Pollutant and Transfer Register (E-PRTR) were combined with population density data (European Environment Agency dataset) and disease frequency data from European health for all database (HfA); uncertainty was assessed via simulation methods. Countries covered by the European Environment Agency's E-PRTR registry on contaminated sites were considered (European Union Member States plus four additional European Countries) for the period 2007-2014. Four outcomes, for which suggestive evidence is available, were included: - low birth weight; - congenital anomalies; - respiratory disease; - annoyance from odour. Firstly, they were analysed separately, in terms of excess number of cases, and then combined into disability-adjusted life years (DALYs).1,544 landfill sites were considered. 29.3 million people (6% of the total population) live within 4 km from one or more of these sites. The number of yearly attributable cases associated with low birth weight, congenital anomalies, respiratory diseases, and annoyance from odour were estimated, respectively, at 1,239, 70, 33,039, and 1,582,624. Associated DALYs were 10,192, 958, 2,688, and 47,505, respectively; 61,325 in total.estimates indicate a sizable health impact, largest for annoyance from odour, given the high frequency of the outcome and in spite of its lesser severity compared to the other ones. Application of the methodology is relatively straightforward, once the main assumption of causality is made. The present work offers a first approximation of the impact on health of waste landfills in Europe and can be further applied to other contaminated sites.