Versatile Biodegradable Poly(acrylic acid)-Based Hydrogels Infiltrated in Porous Titanium Implants to Improve the Biofunctional Performance.

This research work proposes a synergistic approach to improve implants' performance through the use of porous Ti substrates to reduce the mismatch between Young's modulus of Ti (around 110 GPa) and the cortical bone (20-25 GPa), and the application of a biodegradable, acrylic acid-based polymeric coating to reduce bacterial adhesion and proliferation, and to enhance osseointegration. First, porous commercially pure Ti substrates with different porosities and pore size distributions were fabricated by using space-holder techniques to obtain substrates with improved tribomechanical behavior. On the other hand, a new diacrylate cross-linker containing a reduction-sensitive disulfide bond was synthesized to prepare biodegradable poly(acrylic acid)-based hydrogels with 1, 2, and 4% cross-linker. Finally, after the required characterization, both strategies were implemented, and the combination of 4% cross-linked poly(acrylic acid)-based hydrogel infiltrated in 30 vol % porosity, 100-200 µm average pore size, was revealed as an outstanding choice for enhancing implant performance.

Emerging Strategies to Improve the Design and Manufacturing of Biocompatible Therapeutic Materials.

Currently, the field of medicine is drastically advancing, mainly due to the progress in emerging areas such as nanomedicine, regenerative medicine, and personalized medicine. For example, the development of novel drug delivery systems in the form of nanoparticles is improving the liberation, absorption, distribution, metabolism, and excretion (LADME) properties of the derived formulations, with a consequent enhancement in the treatment efficacy, a reduction in the secondary effects, and an increase in compliance with the dosage guidelines. Additionally, the use of biocompatible scaffolds is translating into the possibility of regenerating biological tissues. Personalized medicine is also benefiting from the advantages offered by additive manufacturing. However, all these areas have in common the need to develop novel materials or composites that fulfill the requirements of each application. Therefore, the aim of this Special Issue was to identify novel materials/composites that have been developed with specific characteristics for the designed biomedical application.

Antimicrobial and Antibiofilm Effect of 4,4'-Dihydroxy-azobenzene against Clinically Resistant Staphylococci.

The spread of antibiotic resistance among human and animal pathogens is one of the more significant public health concerns. Moreover, the restrictions on the use of particular antibiotics can limit the options for the treatment of infections in veterinary clinical practice. In this context, searching for alternative antimicrobial substances is crucial nowadays. In this study, 4,4'-dihydroxy-azobenzene (DHAB) was tested for its potential in vitro as an antimicrobial agent against two relevant human and animal pathogens, namely Staphylococcus aureus and Staphylococcus pseudintermedius. The values of minimal inhibitory concentration (MIC) were 64 and 32 mg/L respectively, and they comparable to other azo compounds of probed antimicrobial activity. In addition, the minimal bactericidal concentrations (MCB) were 256 and 64 mg/L. The mechanism by which DHAB produces toxicity in staphylococci has been investigated. DHAB caused membrane damage as revealed by the increase in thiobarbituric acid reactive substances (TBARS) such as malondialdehyde. Furthermore, differential induction of the enzymes peroxidases and superoxide dismutase in S. aureus and S. pseudintermedius suggested their prevalent role in ROS-scavenging due to the oxidative burst induced by this compound in either species. In addition, this substance was able to inhibit the formation of biofilms by both bacteria as observed by colorimetric tests and scanning electron microscopy. In order to assess the relevance of DHAB against clinical strains of MRSA, 10 clinical isolates resistant to either methicillin or daptomycin were assayed; 80% of them gave values of CMI and CMB similar to those of the control S. aureus strain. Finally, cutaneous plasters containing a composite formed by an agar base supplemented with DHAB were designed. These plasters were able to inhibit in vitro the growth of S. aureus and S. pseudintermedius, particularly the later, and this suggests that this substance could be a promising candidate as an alternative to antibiotics in the treatment of animal skin infections, as it has been proven that the toxicity of this substance is very low particularly at a dermal level.

Different Effects of Low Selenite and Selenium-Nanoparticle Supplementation on Adipose Tissue Function and Insulin Secretion in Adolescent Male Rats.

Adolescence is a period of intense growth and endocrine changes, and obesity and insulin-resistance processes during this period have lately been rising. Selenium (Se) homeostasis is related to lipid metabolism depending on the form and dose of Se. This study tests the actions of low-dose selenite and Se nanoparticles (SeNPs) on white (WAT) and brown adipose tissue (BAT) deposition, insulin secretion, and GPx1, IRS-1 and FOXO3a expression in the WAT of adolescent rats as regards oxidative stress, adipocyte length and adipokine secretion. Four groups of male adolescent rats were treated: control (C), low selenite supplementation (S), low SeNP supplementation (NS) and moderate SeNP supplementation (NSS). Supplementation was received orally through water intake; NS and NSS rats received two- and tenfold more Se than C animals, respectively. SeNPs were obtained by reducing Se tetrachloride in the presence of ascorbic acid. For the first time in vivo, it was demonstrated that low selenite supplementation contributed to increased adipogenesis via the insulin signaling pathway and LCN2 modulation, while low SeNP administration prevented fat depots in WAT via the decrease in insulin signaling and FOXO3a autophagy in WAT, lowering inflammation. These effects were independent of GPx1 expression or activity in WAT. These findings provide data for dietary approaches to prevent obesity and/or anorexia during adolescence. These findings may be relevant to future studies looking at a nutritional approach aimed at pre-venting obesity and/or anorexia in adolescence.

Novel Utilization of Therapeutic Coatings Based on Infiltrated Encapsulated Rose Bengal Microspheres in Porous Titanium for Implant Applications.

Despite the increasing progress achieved in the last 20 years in both the fabrication of porous dental implants and the development of new biopolymers for targeting drug therapy, there are important issues such as bone resorption, poor osseointegration, and bacterial infections that remain as critical challenges to avoid clinical failure problems. In this work, we present a novel microtechnology based on polycaprolactone microspheres that can adhere to porous titanium implant models obtained by the spacer holder technique to allow a custom biomechanical and biofunctional balance. For this purpose, a double emulsion solvent evaporation technique was successfully employed for the fabrication of the microparticles properly loaded with the antibacterial therapeutic agent, rose bengal. The resulting microspheres were infiltrated into porous titanium substrate and sintered at 60 °C for 1 h, obtaining a convenient prophylactic network. In fact, the sintered polymeric microparticles were demonstrated to be key to controlling the drug dissolution rate and favoring the early healing process as consequence of a better wettability of the porous titanium substrate to promote calcium phosphate nucleation. Thus, this joint technology proposes a suitable prophylactic tool to prevent both early-stage infection and late-stage osseointegration problems.

Fabrication and Characterization of Bioactive Gelatin-Alginate-Bioactive Glass Composite Coatings on Porous Titanium Substrates.

In this research work, the fabrication of biphasic composite implants has been investigated. Porous, commercially available pure Ti (50 vol % porosity and pore distributions of 100-200, 250-355, and 355-500 µm) has been used as a cortical bone replacement, while different composites based on a polymer blend (gelatin and alginate) and bioactive glass (BG) 45S5 have been applied as a soft layer for cartilage tissues. The microstructure, degradation rates, biofunctionality, and wear behavior of the different composites were analyzed to find the best possible coating. Experiments demonstrated the best micromechanical balance for the substrate containing 200-355 µm size range distribution. In addition, although the coating prepared from alginate presented a lower mass loss, the composite containing 50% alginate and 50% gelatin showed a higher elastic recovery, which entails that this type of coating could replicate the functions of the soft tissue in areas of the joints. Therefore, results revealed that the combinations of porous commercially pure Ti and composites prepared from alginate/gelatin/45S5 BG are candidates for the fabrication of biphasic implants not only for the treatment of osteochondral defects but also potentially for any other diseases affecting simultaneously hard and soft tissues.

Latest Trends in Surface Modification for Dental Implantology: Innovative Developments and Analytical Applications.

An increase in the world population and its life expectancy, as well as the ongoing concern about our physical appearance, have elevated the relevance of dental implantology in recent decades. Engineering strategies to improve the survival rate of dental implants have been widely investigated, focusing on implant material composition, geometry (usually guided to reduce stiffness), and interface surrounding tissues. Although efforts to develop different implant surface modifications are being applied in commercial dental prostheses today, the inclusion of surface coatings has gained special interest, as they can be tailored to efficiently enhance osseointegration, as well as to reduce bacterial-related infection, minimizing peri-implantitis appearance and its associated risks. The use of biomaterials to replace teeth has highlighted the need for the development of reliable analytical methods to assess the therapeutic benefits of implants. This literature review considers the state-of-the-art strategies for surface modification or coating and analytical methodologies for increasing the survival rate for teeth restoration.

Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices.

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.

Native Chilean Berries Preservation and In Vitro Studies of a Polyphenol Highly Antioxidant Extract from Maqui as a Potential Agent against Inflammatory Diseases.

The best conservation method for native Chilean berries has been investigated in combination with an implemented large-scale extract of maqui berry, rich in total polyphenols and anthocyanin to be tested in intestinal epithelial and immune cells. The methanolic extract was obtained from lyophilized and analyzed maqui berries using Folin-Ciocalteu to quantify the total polyphenol content, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) to measure the antioxidant capacity. Determination of maqui's anthocyanins profile was performed by ultra-high-performance liquid chromatography (UHPLC-MS/MS). Viability, cytotoxicity, and percent oxidation in epithelial colon cells (HT-29) and macrophages cells (RAW 264.7) were evaluated. In conclusion, preservation studies confirmed that the maqui properties and composition in fresh or frozen conditions are preserved and a more efficient and convenient extraction methodology was achieved. In vitro studies of epithelial cells have shown that this extract has a powerful antioxidant strength exhibiting a dose-dependent behavior. When lipopolysaccharide (LPS)-macrophages were activated, noncytotoxic effects were observed, and a relationship between oxidative stress and inflammation response was demonstrated. The maqui extract along with 5-aminosalicylic acid (5-ASA) have a synergistic effect. All of the compiled data pointed out to the use of this extract as a potential nutraceutical agent with physiological benefits for the treatment of inflammatory bowel disease (IBD).

Exploiting Generative Design for 3D Printing of Bacterial Biofilm Resistant Composite Devices.

As the understanding of disease grows, so does the opportunity for personalization of therapies targeted to the needs of the individual. To bring about a step change in the personalization of medical devices it is shown that multi-material inkjet-based 3D printing can meet this demand by combining functional materials, voxelated manufacturing, and algorithmic design. In this paper composite structures designed with both controlled deformation and reduced biofilm formation are manufactured using two formulations that are deposited selectively and separately. The bacterial biofilm coverage of the resulting composites is reduced by up to 75% compared to commonly used silicone rubbers, without the need for incorporating bioactives. Meanwhile, the composites can be tuned to meet user defined mechanical performance with ±10% deviation. Device manufacture is coupled to finite element modelling and a genetic algorithm that takes the user-specified mechanical deformation and computes the distribution of materials needed to meet this under given load constraints through a generative design process. Manufactured products are assessed against the mechanical and bacterial cell-instructive specifications and illustrate how multifunctional personalization can be achieved using generative design driven multi-material inkjet based 3D printing.

Erratum: Guillermo M., et al. Environmental Impact of Nanoparticles' Application as an Emerging Technology: A Review. Materials 2021, 14, 166.

The authors wish to make the following corrections to this paper [...].

Author Correction: Design of highly stabilized nanocomposite inks based on biodegradable polymer-matrix and gold nanoparticles for Inkjet Printing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects.

The complexity of some diseases-as well as the inherent toxicity of certain drugs-has led to an increasing interest in the development and optimization of drug-delivery systems. Polymeric nanoparticles stand out as a key tool to improve drug bioavailability or specific delivery at the site of action. The versatility of polymers makes them potentially ideal for fulfilling the requirements of each particular drug-delivery system. In this review, a summary of the state-of-the-art panorama of polymeric nanoparticles as drug-delivery systems has been conducted, focusing mainly on those applications in which the corresponding disease involves an important morbidity, a considerable reduction in the life quality of patients-or even a high mortality. A revision of the use of polymeric nanoparticles for ocular drug delivery, for cancer diagnosis and treatment, as well as nutraceutical delivery, was carried out, and a short discussion about future prospects of these systems is included.

Biofunctional and Tribomechanical Behavior of Porous Titanium Substrates Coated with a Bioactive Glass Bilayer (45S5-1393).

The porous substrates of commercially pure titanium have been coated with a novel bilayer of bioactive glasses (BGs), 45S5 and 1393, to improve the osseointegration and solve the stress-shielding phenomenon of titanium partial implants. The porosity of the substrates and the scratch resistance and bioactivity of the coating have been evaluated. Results are discussed in terms of stiffness and yield strength of the substrates, as well as the chemical composition, thickness, and design of the bioglass coating (monolithic vs bilayer). The role of the pores was a crucial issue in the anchoring of the coating, both in porosity percentage (30 and 60 vol %) and in pore range size (100-200 and 355-500 µm). The study was focused on the adhesion and infiltration of a 1393 bioglass layer (in contact with a porous titanium substrate), in combination with the biofunctionality of the 45S5 bioglass layer (surrounded by the host bone tissue), as 1393 bioglass enhances the adherence, while 45S5 bioglass promotes higher bioactivity. This bioactivity of the raw powder was initially estimated by nuclear magnetic resonance, through the evaluation of the chemical environments, and confirmed by the formation of hydroxyapatite when immersed in a simulated body fluid. The results revealed that the substrate with 30 vol % of porosity and a range of 355-500 µm pore size, coated with this novel BG bilayer, presented the best combination in terms of mechanical and biofunctional properties.

Environmental Impact of Nanoparticles' Application as an Emerging Technology: A Review.

The unique properties that nanoparticles exhibit, due to their small size, are the principal reason for their numerous applications, but at the same time, this might be a massive menace to the environment. The number of studies that assess the possible ecotoxicity of nanomaterials has been increasing over the last decade to determine if, despite the positive aspects, they should be considered a potential health risk. To evaluate their potential toxicity, models are used in all types of organisms, from unicellular bacteria to complex animal species. In order to better understand the environmental consequences of nanotechnology, this literature review aims to describe and classify nanoparticles, evaluating their life cycle, their environmental releasing capacity and the type of impact, particularly on living beings, highlighting the need to develop more severe and detailed legislation. Due to their diversity, nanoparticles will be discussed in generic terms focusing on the impact of a great variety of them, highlighting the most interesting ones for the industry.

Design of highly stabilized nanocomposite inks based on biodegradable polymer-matrix and gold nanoparticles for Inkjet Printing.

Nowadays there is a worldwide growing interest in the Inkjet Printing technology owing to its potentially high levels of geometrical complexity, personalization and resolution. There is also social concern about usage, disposal and accumulation of plastic materials. In this work, it is shown that sugar-based biodegradable polyurethane polymers exhibit outstanding properties as polymer-matrix for gold nanoparticles composites. These materials could reach exceptional stabilization levels, and demonstrated potential as novel robust inks for Inkjet based Printing. Furthermore, a physical comparison among different polymers is discussed based on stability and printability experiments to search for the best ink candidate. The University of Seville logo was printed by employing those inks, and the presence of gold was confirmed by ToF-SIMS. This approach has the potential to open new routes and applications for fabrication of enhanced biomedical nanometallic-sensors using stabilized AuNP.

Glutathione-mediated biodegradable polyurethanes derived from L-arabinitol.

The synthesis, characterization, and some properties of new glutathione-mediated biodegradable sugar-based copolyurethanes are described. These copolyurethanes were obtained by polyaddition reaction of mixtures of 2,2'-dithiodiethanol (DiT) and 2,3,4-tri-O-benzyl-L-arabinitol (ArBn) or 2,3,4-tri-O-methyl-L-arabinitol (ArMe) to 1,6-hexamethylene diisocyanate (HMDI). The copolymer compositions were studied by elemental microanalyses and (1)H NMR, revealing that the content of the copolymer units is in all cases very similar to that of their corresponding feed. The PU(DiT-HMDI) homopolymer exhibited a high crystallinity, but the introduction of the arabinitol-based diols led to a reduction in the crystallinity of the copolymers. In their TG curves, the copolymers exhibited a mixed trend of the related homopolymers, and all of them were thermally stable, with degradation temperatures above 220 degrees C. The degradation properties of the macromolecules under physiological conditions in the presence of glutathione were tested. All the copolyurethanes proved to be biodegradable under the experimental conditions (pH = 7.02 and 37 degrees C). The degradation pattern of the copolymers depended not only on the dithiodiethanol (DiT) reactive units ratio in the polymer backbone, but also on the crystallinity of the macromolecule.