Human T-Cell Responses to Metallic Ion-Doped Bioactive Glasses.

Biomaterials are extensively used as replacements for damaged tissue with bioactive glasses standing out as bone substitutes for their intrinsic osteogenic properties. However, biomaterial implantation has the following risks: the development of implant-associated infections and adverse immune responses. Thus, incorporating metallic ions with known antimicrobial properties can prevent infection, but should also modulate the immune response. Therefore, we selected silver, copper and tellurium as doping for bioactive glasses and evaluated the immunophenotype and cytokine profile of human T-cells cultured on top of these discs. Results showed that silver significantly decreased cell viability, copper increased the T helper (Th)-1 cell percentage while decreasing that of Th17, while tellurium did not affect either cell viability or immune response, as evaluated via multiparametric flow cytometry. Multiplex cytokines assay showed that IL-5 levels were decreased in the copper-doped discs, compared with its undoped control, while IL-10 tended to be lower in the doped glass, compared with the control (plastic) while undoped condition showed lower expression of IL-13 and increased MCP-1 and MIP-1ß secretion. Overall, we hypothesized that the Th1/Th17 shift, and specific cytokine expression indicated that T-cells might cross-activate other cell types, potentially macrophages and eosinophils, in response to the scaffolds.

Anticorrosion and Antimicrobial Tannic Acid-Functionalized Ti-Metallic Glass Ribbons for Dental Abutment.

In this study, a recently reported Ti-based metallic glass (MG), without any toxic element, but with a significant amount of metalloid (Si-Ge-B, 18 atom %) and minor soft element (Sn, 2 atom %), was produced in ribbon form using conventional single-roller melt-spinning. The produced Ti60Zr20Si8Ge7B3Sn2 ribbons were investigated by differential scanning calorimetry and X-ray diffraction to confirm their amorphous structure, and their corrosion properties were further investigated by open-circuit potential and cyclic polarization tests. The ribbon's surface was functionalized by tannic acid, a natural plant-based polyphenol, to enhance its performance in terms of corrosion prevention and antimicrobial efficacy. These properties can potentially be exploited in the premucosal parts of dental implants (abutments). The Folin and Ciocalteu test was used for the quantification of tannic acid (TA) grafted on the ribbon surface and of its redox activity. Fluorescent microscopy and ζ-potential measurements were used to confirm the presence of TA on the surfaces of the ribbons. The cytocompatibility evaluation (indirect and direct) of TA-functionalized Ti60Zr20Si8Ge7B3Sn2 MG ribbons toward primary human gingival fibroblast demonstrated that no significant differences in cell viability were detected between the functionalized and as-produced (control) MG ribbons. Finally, the antibacterial investigation of TA-functionalized samples against Staphylococcus aureus demonstrated the specimens' antimicrobial properties, shown by scanning electron microscopy images after 24 h, presenting a few single colonies remaining on their surfaces. The thickness of bacterial aggregations (biofilm-like) that were formed on the surface of the as-produced samples reduced from 3.5 to 1.5 µm.

Nano-topography and functionalization with the synthetic peptoid GN2-Npm9 as a strategy for antibacterial and biocompatible titanium implants.

In recent years, antimicrobial peptides (AMPs) have attracted great interest in scientific research, especially for biomedical applications such as drug delivery and orthopedic applications. Since they are readily degradable in the physiological environment, scientific research has recently been trying to make AMPs more stable. Peptoids are synthetic N-substituted glycine oligomers that mimic the structure of peptides. They have a structure that does not allow proteolytic degradation, which makes them more stable while maintaining microbial activity. This structure also brings many advantages to the molecule, such as greater diversity and specificity, making it more suitable for biological applications. For the first time, a synthesized peptoid (GN2-Npm9) was used to functionalize a nanometric chemically pre-treated (CT) titanium surface for bone-contact implant applications. A preliminary characterization of the functionalized surfaces was performed using the contact angle measurements and zeta potential titration curves. These preliminary analyses confirmed the presence of the peptoid and its adsorption on CT. The functionalized surface had a hydrophilic behaviour (contact angle = 30°) but the hydrophobic tryptophan-like residues were also exposed. An electrostatic interaction between the lysine residue of GN2-Npm9 and the surface allowed a chemisorption mechanism. The biological characterization of the CT_GN2-Nmp9 surfaces demonstrated the ability to prevent surface colonization and biofilm formation by the pathogens Escherichia coli and Staphylococcus epidermidis thus showing a broad-range activity. The cytocompatibility was confirmed by human mesenchymal stem cells. Finally, a bacteria-cells co-culture model was applied to demonstrate the selective bioactivity of the CT_GN2-Nmp9 surface that was able to preserve colonizing cells adhered to the device surface from bacterial infection.

Characterization of Tannic Acid-Coated AZ31 Mg Alloy for Biomedical Application and Comparison with AZ91.

Magnesium alloys are promising materials for bioresorbable implants that will improve patient life and reduce healthcare costs. However, their clinical use is prevented by the rapid degradation and corrosion of magnesium, which leads to a fast loss of mechanical strength and the formation of by-products that can trigger tissue inflammation. Here, a tannic acid coating is proposed to control the degradation of AZ31 and AZ91 alloys, starting from a previous study by the authors on AZ91. The coatings on the two materials were characterized both by the chemical (EDS, FTIR, XPS) and the morphological (SEM, confocal profilometry) point of view. Static degradation tests in PBS and electrochemical measurements in different solutions showed that the protective performances of the tannic acid coatings are strongly affected by the presence of cracks. The presence of fractures in the protective layer generates galvanic couples between the coating scales and the metal, worsening the corrosion resistance. Although degradation control was not achieved, useful insights on the degradation mechanisms of coated Mg surfaces were obtained, as well as key points for future studies: it resulted that the absence of cracks in protective coatings is of uttermost importance for novel biodegradable implants with proper degradation kinetics.

Ce-doped MgO films on AZ31 alloy substrate for biomedical applications: preparation, characterization and testing.

Magnesium ions, MgO nanoparticles and thin films, magnesium alloys and cerium compounds are materials intensively studied due to their corrosion protection, antibacterial and pharmacological properties. In this work, we have designed, prepared and investigated, novel thin films of MgO doped with cerium, deposited on Mg alloy (AZ31) for temporary implants, in order to enhance their life time. More precisely, we report on microstructure and corrosion behavior of MgO pure and doped with 0.1 at % Ce films, fabricated by sol-gel route coupled with spin-coating technique, on AZ31 alloy substrate. A modified sol-gel method that start from magnesium acetylacetonate, cerium nitrate and 2-methoxyethanol (as a stabilizer for the sol) was been used successfully for cerium doped MgO sol precursor preparation. The structure and morphology of the surface of the coatings, before and after immersion for 7-30 d in Hank's solution at 37 °C, were characterized by x-ray diffraction (XRD), scanning electron microscopy, high-resolution transmission electron microscope, x-ray photoelectron spectroscopy and Fourier infrared transmittance spectrum (FT-IR). A comparison between the corrosion protection of undoped MgO and MgO doped with 0.1 at % Ce coatings on the AZ31 alloy substrate is performed by electrochemical tests and immersion tests using open circuit potential and electrochemical impedance spectroscopy in Hank's solution, at 37 °C. The electrochemical results showed that the protection of the AZ31 alloy substrate against corrosion was better with the doped with 0.1 at % Ce MgO film deposited than with pure MgO coting. The investigations of the films after immersion in Hank's solution, at 37 °C, for 7, 21 and 30 d indicated that the grown layer on the film is bone like apatite that suggests a good bioactivity of 0.1 at % Ce-doped MgO coating. Our work demonstrates that the performance corrosion protection of the biodegradable magnesium alloys used for orthopedic applications, in simulated physiological environments (Hank and Ringer) can be enhanced through coating with Ce3+doped MgO sol-gel thin film.

Deposition of Antioxidant and Cytocompatible Caffeic Acid-Based Thin Films onto Ti6Al4V Alloys through Hexamethylenediamine-Mediated Crosslinking.

A promising approach for advanced bone implants is the deposition on titanium surfaces of organic thin films with improved therapeutic performances. Herein, we reported the efficient dip-coating deposition of caffeic acid (CA)-based films on both polished and chemically pre-treated Ti6Al4V alloys by exploiting hexamethylenediamine (HMDA) crosslinking ability. The formation of benzacridine systems, resulting from the interaction of CA with the amino groups of HMDA, as reported in previous studies, was suggested by the yellow/green color of the coatings. The coated surfaces were characterized by means of the Folin-Ciocalteu method, fluorescence microscopy, water contact angle measurements, X-ray photoelectron spectroscopy (XPS), zeta-potential measurements, and Fourier transform infrared spectroscopy, confirming the presence of a uniform coating on the titanium surfaces. The optimal mechanical adhesion of the coating, especially on the chemically pre-treated substrate, was also demonstrated by the tape adhesion test. Interestingly, both films exhibited marked antioxidant properties (2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays) that persisted over time and were not lost even after prolonged storage of the material. The feature of the coatings in terms of the exposed groups (XPS and zeta potential titration evidence) was apparently dependent on the surface pre-treatment of the titanium substrate. Cytocompatibility, scavenger antioxidant activity, and antibacterial properties of the developed coatings were evaluated. The most promising results were obtained in the case of the chemically pre-treated CA/HMDA-based coated surface that showed good cytocompatibility and high reactive oxygen species' scavenging ability, preventing their intracellular accumulation under pro-inflammatory conditions; moreover, an anti-fouling effect preventing the formation of 3D biofilm-like bacterial aggregates was observed by scanning electron microscopy. These results open new perspectives for the development of innovative titanium surfaces with thin coatings from naturally occurring phenols for bone contact implants.

Influence of a Physiologically Formed Blood Clot on Pre-Osteoblastic Cells Grown on a BMP-7-Coated Nanoporous Titanium Surface.

Titanium (Ti) nanotopography modulates the osteogenic response to exogenous bone morphogenetic protein 7 (BMP-7) in vitro, supporting enhanced alkaline phosphatase mRNA expression and activity, as well as higher osteopontin (OPN) mRNA and protein levels. As the biological effects of OPN protein are modulated by its proteolytic cleavage by serum proteases, this in vitro study evaluated the effects on osteogenic cells in the presence of a physiological blood clot previously formed on a BMP-7-coated nanostructured Ti surface obtained by chemical etching (Nano-Ti). Pre-osteoblastic MC3T3-E1 cells were cultured during 5 days on recombinant mouse (rm) BMP-7-coated Nano-Ti after it was implanted in adult female C57BI/6 mouse dorsal dermal tissue for 18 h. Nano-Ti without blood clot or with blood clot at time 0 were used as the controls. The presence of blood clots tended to inhibit the expression of key osteoblast markers, except for Opn, and rmBMP-7 functionalization resulted in a tendency towards relatively greater osteoblastic differentiation, which was corroborated by runt-related transcription factor 2 (RUNX2) amounts. Undetectable levels of OPN and phosphorylated suppressor of mothers against decapentaplegic (SMAD) 1/5/9 were noted in these groups, and the cleaved form of OPN was only detected in the blood clot immediately prior to cell plating. In conclusion, the strategy to mimic in vitro the initial interfacial in vivo events by forming a blood clot on a Ti nanoporous surface resulted in the inhibition of pre-osteoblastic differentiation, which was minimally reverted with an rmBMP-7 coating.

Conferring Antioxidant Activity to an Antibacterial and Bioactive Titanium Surface through the Grafting of a Natural Extract.

The main unmet medical need of bone implants is multifunctional activity, including their ability to induce rapid and physiological osseointegration, counteract bacterial biofilm formation, and prevent in situ chronic inflammation at the same time. This research starts from an already developed c.p. titanium surface with proven bioactive (in vitro hydroxyl apatite precipitation) and antibacterial activities, due to a calcium titanate layer with nano- and micro-scale roughness and loaded with iodine ions. Here, antioxidant ability was added to prevent chronic inflammation by grafting polyphenols of a green tea extract onto the surface, without compromising the other functionalities of the surface. The surface was characterized before and after functionalization through XPS analysis, zeta potential titrations, ion release measurements, in vitro bioactivity tests, SEM and fluorescence microscopy, and Folin-Ciocalteu and biological tests. The presence of grafted polyphenols as a homogeneous layer was proven. The grafted polyphenols maintained their antioxidant ability and were anchored to the surface through the linking action of Ca2+ ions added to the functionalizing solution. Iodine ion release, cytocompatibility towards human mesenchymal stem cells (hMSC), and antibacterial activity were maintained even after functionalization. The antioxidant ability of the functionalized surface was effective in preserving hMSC viability in a chemically induced pro-inflammatory environment, thus showing a scavenger activity towards toxic active species responsible for inflammation.

Surface Functionalization of Ti6Al4V-ELI Alloy with Antimicrobial Peptide Nisin.

Implant-associated infections are a severe global concern, especially in the case of orthopedic implants intended for long-term or permanent use. The traditional treatment through systemic antibiotic administration is often inefficient due to biofilm formation, and concerns regarding the development of highly resistant bacteria. Therefore, there is an unfulfilled need for antibiotic-free alternatives that could simultaneously support bone regeneration and prevent bacterial infection. This study aimed to perform, optimize, and characterize the surface functionalization of Ti6Al4V-ELI discs by an FDA-approved antimicrobial peptide, nisin, known to hold a broad antibacterial spectrum. Accordingly, nisin bioactivity was also evaluated by in vitro release tests both in physiological and inflammatory pH conditions. Several methods, such as X-ray photoelectron spectroscopy (XPS), and Kelvin Probe atomic force microscopy confirmed the presence of a physisorbed nisin layer on the alloy surface. The functionalization performed at pH 6-7 was found to be especially effective due to the nisin configuration exposing its hydrophobic tail outwards, which is also responsible for its antimicrobial action. In addition, the first evidence of gradual nisin release both in physiological and inflammatory conditions was obtained: the static contact angle becomes half of the starting one after 7 days of soaking on the functionalized sample, while it becomes 0° on the control samples. Finally, the evaluation of the antibacterial performance toward the pathogen Staphylococcus aureus after 24 h of inoculation showed the ability of nisin adsorbed at pH 6 to prevent bacterial microfouling into biofilm-like aggregates in comparison with the uncoated specimens: viable bacterial colonies showed a reduction of about 40% with respect to the un-functionalized surface and the formation of (microcolonies (biofilm-like aggregates) is strongly affected.

UV-Cured Chitosan-Based Hydrogels Strengthened by Tannic Acid for the Removal of Copper Ions from Water.

In this work, a new environmentally friendly material for the removal of heavy metal ions was developed to enhance the adsorption efficiency of photocurable chitosan-based hydrogels (CHg). The acknowledged affinity of tannic acid (TA) to metal ions was investigated to improve the properties of hydrogels obtained from natural and renewable sources (CHg-TA). The hydrogel preparation was performed via a simple two-step method consisting of the photocrosslinking of methacrylated chitosan and its subsequent swelling in the TA solution. The samples were characterized using ATR-FTIR, SEM, and Folin-Ciocalteu (F&C) assay. Moreover, the mechanical properties and the ζ potential of CHg and CHg-TA were tested. The copper ion was selected as a pollutant model. The adsorption capacity (Qe) of CHg and CHg-TA was assessed as a function of pH. Under acidic conditions, CHg-TA shows a higher Qe than CHg through the coordination of copper ions by TA. At an alkaline pH, the phenols convert into a quinone form, decreasing the Qe of CHg-TA, and the performance of CHg was found to be improved. A partial TA release can occur in the copper solution due to its high hydrophilicity and strong acidic pH conditions. Additionally, the reusability of hydrogels was assessed, and the high number of recycling cycles of CHg-TA was related to its high mechanical performance (compression tests). These findings suggest CHg-TA as a promising green candidate for heavy metal ion removal from acidic wastewater.

Functionalization with Polyphenols of a Nano-Textured Ti Surface through a High-Amino Acid Medium: A Chemical-Physical and Biological Characterization.

The study aimed to identify an effective mechanism of adsorption of polyphenols on a nano-textured Ti surface and to evaluate the osteogenic differentiation on it. The source of polyphenols was a natural extract from red grape pomace. A chemical etching was used to form an oxide layer with a nanoscale texture on Ti; this layer is hydrophilic, but without hydroxyl groups with high acidic-basic chemical reactivity. The samples were characterized by electron and fluorescence microscopies, UV-Vis spectroscopy, contact angle measurements, zeta potential titration curves, and Folin-Ciocâlteu test. The presence of an adsorbed layer of polyphenols on the functionalized surface, maintaining redox ability, was confirmed by several tests. Consistent with the surface features, the adsorption was maximized by dissolving the extract in a high-amino acid medium, with respect to an inorganic solution, exploiting the high affinity of amino acids for polyphenols and for porous titanium surfaces. The osteogenic differentiation was assessed on an osteoblastic cell line by immunofluorescence, cell viability, expression of key osteoblast markers, and extracellular matrix mineralization. The surfaces functionalized with the extract diluted in the range 1 × 10-5-1 mg/mL resulted in having a greater osteogenic activity for the highest concentration, with lower values of cell viability; higher expression of alkaline phosphatase, bone sialoprotein, and collagen; and lower levels of osteopontin. In conclusion, the functionalization of a nano-textured Ti surface with polyphenols can potentially favor the osteogenic activity of osseointegrated implants.

Effects of rmBMP-7 on Osteoblastic Cells Grown on a Nanostructured Titanium Surface.

This study evaluates the effects of the availability of exogenous BMP-7 on osteoblastic cells' differentiation on a nanotextured Ti surface obtained by chemical etching (Nano-Ti). The MC3T3-E1 and UMR-106 osteoblastic cell lines were cultured for 5 and 7 days, respectively, on a Nano-Ti surface and on a control surface (Control-Ti) in an osteogenic medium supplemented with either 40 or 200 ng/mL recombinant mouse (rm) BMP-7. The results showed that MC3T3-E1 cells exhibited distinct responsiveness when exposed to each of the two rmBMP-7 concentrations, irrespective of the surface. Even with 40 ng/mL rmBMP-7, important osteogenic effects were noticed for Control-Ti in terms of cell proliferation potential; Runx2, Osx, Alp, Bsp, Opn, and Smad1 mRNA expression; and in situ ALP activity. For Nano-Ti, the effects were limited to higher Alp, Bsp, and Opn mRNA expression and in situ ALP activity. On both surfaces, the osteogenic potential of UMR-106 cultures remained unaltered with 40 ng/mL rmBMP-7, but it was significantly reduced when the cultures were exposed to the 200 ng/mL concentration. The availability of rmBMP-7 to pre-osteoblastic cells at the concentrations used alters the expression profile of osteoblast markers, indicative of the acquisition of a more advanced stage of osteoblastic differentiation. This occurs less pronouncedly on the nanotextured Ti and without reflecting in higher mineralized matrix production by differentiated osteoblasts on both surfaces.

Polyphenols from Grape Pomace: Functionalization of Chitosan-Coated Hydroxyapatite for Modulated Swelling and Release of Polyphenols.

Chitosan is known for its specific antibacterial mechanism and biodegradability, while polyphenols are known for their antioxidant and anti-inflammatory properties: coupling these properties on a surface for bone contact, such as hydroxyapatite, is of great interest. The system developed here allows the combination of hydroxyapatite, chitosan, and polyphenol properties in the same multifunctional biomaterial in order to modulate the host response after implantation. Crosslinked chitosan is used in this research to create a stable coating on hydroxyapatite, and then it is functionalized for a smart release of the polyphenols. The release is higher in inflammatory conditions and lower in physiological conditions. The properties of the coated and functionalized samples are characterized on the as-prepared samples and after the samples are immersed (for 24 h) in solutions, which simulate the inflammatory and physiological conditions. Characterization is performed in order to confirm the presence of polyphenols grafted within the chitosan coating, the stability of grafting as a function of pH, the morphology of the coating and distribution of polyphenols on the surface, and the redox reactivity and radical scavenging activity of the functionalized coating. All the results are in line with previous results, which show a successful coating with chitosan and functionalization with polyphenols. Moreover, the polyphenols have a different release kinetics that is faster in a simulated inflammatory environment compared to that in the physiological environment. Even after the release tests, a fraction of polyphenols are still bound on the surface, maintaining the antioxidant and radical scavenging activity for a longer time. An electrostatic bond occurs between the negative-charged polar groups of polyphenols (carboxyls and/or phenols) and the positive amide groups of the chitosan coating, and the substitution of the crosslinker by the polyphenols occurs during the functionalization process.

Iodine-Loaded Calcium Titanate for Bone Repair with Sustainable Antibacterial Activity Prepared by Solution and Heat Treatment.

In the orthopedic and dental fields, simultaneously conferring titanium (Ti) and its alloy implants with antibacterial and bone-bonding capabilities is an outstanding challenge. In the present study, we developed a novel combined solution and heat treatment that controllably incorporates 0.7% to 10.5% of iodine into Ti and its alloys by ion exchange with calcium ions in a bioactive calcium titanate. The treated metals formed iodine-containing calcium-deficient calcium titanate with abundant Ti-OH groups on their surfaces. High-resolution XPS analysis revealed that the incorporated iodine ions were mainly positively charged. The surface treatment also induced a shift in the isoelectric point toward a higher pH, which indicated a prevalence of basic surface functionalities. The Ti loaded with 8.6% iodine slowly released 5.6 ppm of iodine over 90 days and exhibited strong antibacterial activity (reduction rate >99%) against methicillin-resistant Staphylococcus aureus (MRSA), S. aureus, Escherichia coli, and S. epidermidis. A long-term stability test of the antibacterial activity on MRSA showed that the treated Ti maintained a >99% reduction until 3 months, and then it gradually decreased after 6 months (to a 97.3% reduction). There was no cytotoxicity in MC3T3-E1 or L929 cells, whereas apatite formed on the treated metal in a simulated body fluid within 3 days. It is expected that the iodine-carrying Ti and its alloys will be particularly useful for orthopedic and dental implants since they reliably bond to bone and prevent infection owing to their apatite formation, cytocompatibility, and sustainable antibacterial activity.

Vitamin E: A Review of Its Application and Methods of Detection When Combined with Implant Biomaterials.

Vitamin E is a common compound used for tocopherols and tocotrienols (α, ß, γ, δ); it is the component of many natural products of both plant and animal origin. Thanks to its powerful antioxidant capacity, vitamin E has been very successful in hip and knee arthroplasty, used to confer resistance to oxidation to irradiated UHMWPE. The positive results of these studies have made vitamin E an important object of research in the biomedical field, highlighting other important properties, such as anti-bacterial, -inflammatory, and -cancer activities. In fact, there is an extensive literature dealing with vitamin E in different kinds of material processing, drug delivery, and development of surface coatings. Vitamin E is widely discussed in the literature, and it is possible to find many reviews that discuss the biological role of vitamin E and its applications in food packaging and cosmetics. However, to date, there is not a review that discusses the biomedical applications of vitamin E and that points to the methods used to detect it within a solid. This review specifically aims to compile research about new biomedical applications of vitamin E carried out in the last 20 years, with the intention of providing an overview of the methodologies used to combine it with implantable biomaterials, as well as to detect and characterize it within these materials.

Contact Guidance Effect and Prevention of Microfouling on a Beta Titanium Alloy Surface Structured by Electron-Beam Technology.

Nano- and micro-structuring of implantable materials constitute a promising approach to introduce mechanical contact guidance effect, drive cells colonization, as well as to prevent bacteria adhesion and biofilm aggregation, through antifouling topography. Accordingly, this paper aims to extend the application of e-beam surface texturing and nano-structuring to the beta titanium alloys, which are of great interest for biomedical implants because of the low Young modulus and the reduction of the stress shielding effect. The paper shows that surface texturing on the micro-scale (micro-grooves) is functional to a contact guidance effect on gingival fibroblasts. Moreover, nano-structuring, derived from the e-beam surface treatment, is effective to prevent microfouling. In fact, human fibroblasts were cultivated directly onto grooved specimens showing to sense the surface micro-structure thus spreading following the grooves' orientation. Moreover, Staphylococcus aureus colonies adhesion was prevented by the nano-topographies in comparison to the mirror-polished control, thus demonstrating promising antifouling properties. Furthermore, the research goes into detail to understand the mechanism of microfouling prevention due to nano-topography and microstructure.

Titanium and Protein Adsorption: An Overview of Mechanisms and Effects of Surface Features.

Titanium and its alloys, specially Ti6Al4V, are among the most employed materials in orthopedic and dental implants. Cells response and osseointegration of implant devices are strongly dependent on the body-biomaterial interface zone. This interface is mainly defined by proteins: They adsorb immediately after implantation from blood and biological fluids, forming a layer on implant surfaces. Therefore, it is of utmost importance to understand which features of biomaterials surfaces influence formation of the protein layer and how to guide it. In this paper, relevant literature of the last 15 years about protein adsorption on titanium-based materials is reviewed. How the surface characteristics affect protein adsorption is investigated, aiming to provide an as comprehensive a picture as possible of adsorption mechanisms and type of chemical bonding with the surface, as well as of the characterization techniques effectively applied to model and real implant surfaces. Surface free energy, charge, microroughness, and hydroxylation degree have been found to be the main surface parameters to affect the amount of adsorbed proteins. On the other hand, the conformation of adsorbed proteins is mainly dictated by the protein structure, surface topography at the nano-scale, and exposed functional groups. Protein adsorption on titanium surfaces still needs further clarification, in particular concerning adsorption from complex protein solutions. In addition, characterization techniques to investigate and compare the different aspects of protein adsorption on different surfaces (in terms of roughness and chemistry) shall be developed.

3D Printing of PDMS-Like Polymer Nanocomposites with Enhanced Thermal Conductivity: Boron Nitride Based Photocuring System.

This study demonstrates the possibility of forming 3D structures with enhanced thermal conductivity (k) by vat printing a silicone-acrylate based nanocomposite. Polydimethylsiloxane (PDSM) represent a common silicone-based polymer used in several applications from electronics to microfluidics. Unfortunately, the k value of the polymer is low, so a composite is required to be formed in order to increase its thermal conductivity. Several types of fillers are available to reach this result. In this study, boron nitride (BN) nanoparticles were used to increase the thermal conductivity of a PDMS-like photocurable matrix. A digital light processing (DLP) system was employed to form complex structures. The viscosity of the formulation was firstly investigated; photorheology and attenuate total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) analyses were done to check the reactivity of the system that resulted as suitable for DLP printing. Mechanical and thermal analyses were performed on printed samples through dynamic mechanical thermal analysis (DMTA) and tensile tests, revealing a positive effect of the BN nanoparticles. Morphological characterization was performed by scanning electron microscopy (SEM). Finally, thermal analysis demonstrated that the thermal conductivity of the material was improved, maintaining the possibility of producing 3D printable formulations.

Surface Functionalization of a Silica-Based Bioactive Glass with Compounds from Rosa canina Bud Extracts.

Bud extracts are a new category of vegetal products, which are used in gemmotherapy. These products are liquid preparation sources of bioactive molecules (phytochemicals) and are used in medicine as health-promoting agents. Rosa canina is a medicinal plant belonging to the family Rosaceae. The R. canina bud extracts, in particular, possess anti-inflammatory and antioxidant activities due to the presence of flavonoids and other phenolic compounds. The combination of R. canina bud extracts with biomaterials can be promising for obtaining multifunctional materials carrying both inorganic and biological properties. In this work, a protocol of functionalization has been properly designed, for the first time in the literature, in order to graft various bud extracts of R. canina to a silica-based bioactive glass (CEL2). The Folin-Ciocalteu method was used to determine the redox capacity of total polyphenols in the extracts and on functionalized solid samples. X-ray photoelectron spectroscopy analysis and fluorescence microscopy were employed to investigate the presence of phenol substances on the material surface. Bioactivity (in terms of ability of inducing hydroxyapatite precipitation) has been investigated by soaking the samples, with or without functionalization, in simulated body fluid. The presence of the polyphenols from bud extracts not only preserved glass bioactivity but even enhanced it. In particular, the solution obtained from the byproducts of primary extraction in glycerol macerate showed the best performances. Moreover, the presence and antioxidant activity of bud extract compounds on the material surface after grafting demonstrate the possibility of combining the glass inorganic bioactivity with the biomolecule-specific properties, making possible a local action at the implant site. The promising results reported in this work pave the way for the realization of new multifunctional materials with a green approach.

Topographical and Biomechanical Guidance of Electrospun Fibers for Biomedical Applications.

Electrospinning is gaining increasing interest in the biomedical field as an eco-friendly and economic technique for production of random and oriented polymeric fibers. The aim of this review was to give an overview of electrospinning potentialities in the production of fibers for biomedical applications with a focus on the possibility to combine biomechanical and topographical stimuli. In fact, selection of the polymer and the eventual surface modification of the fibers allow selection of the proper chemical/biological signal to be administered to the cells. Moreover, a proper design of fiber orientation, dimension, and topography can give the opportunity to drive cell growth also from a spatial standpoint. At this purpose, the review contains a first introduction on potentialities of electrospinning for the obtainment of random and oriented fibers both with synthetic and natural polymers. The biological phenomena which can be guided and promoted by fibers composition and topography are in depth investigated and discussed in the second section of the paper. Finally, the recent strategies developed in the scientific community for the realization of electrospun fibers and for their surface modification for biomedical application are presented and discussed in the last section.