Self-healing layer on non-ferrous metals using polyoxometalates

The invention relates to a method for applying a multifunctional layer on a substrate. Accordingly said layer is applied by means of a process by using an aqueous solution that comprises a POM and/or a crack-healing agent, which POM and/or a crack healing agent is/are incorporated in said layer during said process to obtain a self-healing layer.Mechanical, Maritime and Materials Engineerin

Synthesis and characterisation of autocatalytic nickel composite coatings on aluminium

Applied Science

High-Precision 3D Printing of Microporous Cochlear Implants for Personalized Local Drug Delivery

Hearing loss is a highly prevalent multifactorial disorder affecting 20% of the global population. Current treatments using the systemic administration of drugs are therapeutically ineffective due to the anatomy of the cochlea and the existing blood–labyrinth barrier. Local drug delivery systems can ensure therapeutic drug concentrations locally while preventing adverse effects caused by high dosages of systemically administered drugs. Here, we aimed to design, fabricate, and characterize a local drug delivery system for the human cochlea. The design was relevant to the size of the human ear, included two different shapes, and incorporated two different microporous structures acting as reservoirs for drug loading and release. The four cochlear implant designs were printed using the two-photon polymerization (2PP) technique and the IP-Q photoresist. The optimized 2PP process enabled the fabrication of the cochlear implants with great reproducibility and shape fidelity. Rectangular and cylindrical implants featuring cylindrical and tapered tips, respectively, were successfully printed. Their outer dimensions were 0.6 × 0.6 × 2.4 mm3 (L × W × H). They incorporated internal porous networks that were printed with high accuracy, yielding pore sizes of 17.88 ± 0.95 μm and 58.15 ± 1.62 μm for the designed values of 20 μm and 60 μm, respectively. The average surface roughness was 1.67 ± 0.24 μm, and the water contact angle was 72.3 ± 3.0°. A high degree of polymerization (~90%) of the IP-Q was identified after printing, and the printed material was cytocompatible with murine macrophages. The cochlear implants designed and 3D printed in this study, featuring relevant sizes for the human ear and tunable internal microporosity, represent a novel approach for personalized treatment of hearing loss through local drug delivery.Biomaterials & Tissue Biomechanic

Enrichment of anodic MgO layers with Ag nanoparticles for biomedical applications

The growing fight against infections caused by bacteria poses new challenges for development of materials and medical devices with antimicrobial properties. Silver is a well known antimicrobial agent and has recently started to be used in nanoparticulate form, with the advantage of a high specific surface area and a continuous release of enough concentration of silver ions/radicals. The synthesis of MgO–Ag nanocomposite coatings by in situ deposition of silver nanoparticles during plasma electrolytic oxidation of a magnesium substrate is presented in this study. The process was performed in an electrolyte containing Ag nanoparticles under different oxidation conditions (i.e., current density, oxidizing time, silver nanoparticles concentration in the electrolyte). Surface morphology, phase composition and elemental composition (on the surface and across the thickness of MgO–Ag nanocomposite coatings) were assessed by scanning electron microscopy, X-ray diffraction, energy X-ray dispersive spectrometry and radio frequency glow discharge optical emission spectroscopy, respectively. The coatings were found to be porous, around 7 µm thick, consisting of a crystalline oxide matrix embedded with silver nanoparticles. The findings suggest that plasma electrolytic oxidation process has potential for the synthesis of MgO–Ag nanocomposite coatings.Materials Science and EngineeringMechanical, Maritime and Materials Engineerin

Size effect of PLGA spheres on drug loading efficiency and release profiles

Drug delivery systems (DDS) based on poly (lactide-co-glycolide) (PLGA) microspheres and nanospheres have been separately studied in previous works as a means of delivering bioactive compounds over an extended period of time. In the present study, two DDS having different sizes of the PLGA spheres were compared in morphology, drug (dexamethasone) loading efficiency and drug release kinetics in order to investigate their feasibility with regard to production of medical combination devices for orthopedic applications. The loaded PLGA spheres have been produced by the oil-in-water emulsion/solvent evaporation method following two different schemes. Their morphology was assessed by scanning electron microscopy and the drug release was monitored in phosphate buffer saline solution at 37°C for 550 h using high performance liquid chromatography. The synthesis schemes used produced spheres with two different and reproducible size ranges (20 ± 10 and 1.0 ± 0.4 ?m) having a smooth outer surface and regular shape. The drug loading efficiency of the 1.0 ?m spheres was found to be 11% as compared to just 1% for the 20 ?m spheres. Over the 550 h release period, the larger spheres (diameter 20 ± 10 ?m) released 90% of the encapsulated dexamethasone in an approximately linear fashion whilst the relatively small spheres (diameter 1.0 ± 0.4 ?m) released only 30% of the initially loaded dexamethasone, from which 20% within the first 25 h. The changes observed were mainly attributed to the difference in surface area between the two types of spheres as the surface texture of both systems was visibly similar. As the surface area per unit volume increases in the synthesis mixture, as is the case for the 1.0 ?m spheres formulation, the amount of polymer-water interfaces increases allowing more dexamethasone to be encapsulated by the emerging polymer spheres. Similarly, during the release phase, as the surface area per unit volume increases, the rate of inclusion of water into the polymer increases, permitting faster diffusion of dexamethasone.Materials Science and EngineeringMechanical, Maritime and Materials Engineerin

Antibacterial Titanium Implants Biofunctionalized by Plasma Electrolytic Oxidation with Silver, Zinc, and Copper: A Systematic Review

Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against S. aureus. Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.Biomaterials & Tissue Biomechanic

The effects of plasma electrolytically oxidized layers containing Sr and Ca on the osteogenic behavior of selective laser melted Ti6Al4V porous implants

Surface biofunctionalization is frequently applied to enhance the functionality and longevity of orthopedic implants. Here, we investigated the osteogenic effects of additively manufactured porous Ti6Al4V implants whose surfaces were biofunctionalized using plasma electrolytic oxidation (PEO) in Ca/P-based electrolytes with or without strontium. Various levels of Sr and Ca were incorporated in the oxide layers by using different current densities and oxidation times. Increasing the current density and oxidation time resulted in thicker titanium oxide layers and enhanced the release of Ca2+ and Sr2+. Biofunctionalization with strontium resulted in enhanced pore density, a thinner TiO2 layer, four-fold reduced release of Ca2+, and mainly anatase phases as compared to implants biofunctionalized in electrolytes containing solely Ca/P species under otherwise similar conditions. Different current densities and oxidation times significantly increased the osteogenic differentiation of MC3T3-E1 cells on implants biofunctionalized with strontium, when the PEO treatment was performed with a current density of 20 A/dm2 for 5 and 10 min as well as for a current density of 40 A/dm2 for 5 min. Therefore, addition of Sr in the PEO electrolyte and control of the PEO processing parameters represent a promising way to optimize the surface morphology and osteogenic activity of future porous AM implants.Biomaterials & Tissue Biomechanic

On-Demand Magnetically-Activated Drug Delivery from Additively Manufactured Porous Bone Implants to Tackle Antibiotic-Resistant Infections

This study proposes a new concept for an on-demand drug releasing device intended for integration into additively manufactured (i.e., 3D printed) orthopedic implants. The system comprises a surface with conduits connected to a subsurface reservoir used for storage and on-demand release of antimicrobial agents, covered with a cap that prevents the antibacterial agents from being released until alternating magnetic field (AMF) raises the temperature of the cap, thus, releasing the stored drug. To demonstrate this concept, Ti6Al4V specimens are directly 3D printed using selective laser melting and their surface, reservoirs, and drug releasing properties are characterized. A new synthetic antimicrobial peptide, SAAP-148, is thereafter tested for its cytotoxic, osteogenic, and immunomodulatory effects at concentrations relevant for its minimal bactericidal concentration (MBC) and is compared with its natural analogue, LL-37. The results showed that AMF successfully activated the release from the 3D printed loaded samples. Both peptides demonstrated to be non-cytotoxic within the MBC levels for macrophages and preosteoblasts and did not influence their osteoimmunomodulatory behavior. The findings of this study indicate that the proposed concept is technically feasible and has the potential to be used for the development of bone implants with on-demand delivery systems to fight IAI without systemic or continuous local release of antibiotics.Biomaterials & Tissue Biomechanic

Inorganic Agents for Enhanced Angiogenesis of Orthopedic Biomaterials

Aseptic loosening of a permanent prosthesis remains one of the most common reasons for bone implant failure. To improve the fixation between implant and bone tissue as well as enhance blood vessel formation, bioactive agents are incorporated into the surface of the biomaterial. This study reviews and compares five bioactive elements (copper, magnesium, silicon, strontium, and zinc) with respect to their effect on the angiogenic behavior of endothelial cells (ECs) when incorporated on the surface of biomaterials. Moreover, it provides an overview of the state-of-the-art methodologies used for the in vitro assessment of the angiogenic properties of these elements. Two databases are searched using keywords containing ECs and copper, magnesium, silicon, strontium, and zinc. After applying the defined inclusion and exclusion criteria, 59 articles are retained for the final assessment. An overview of the angiogenic properties of five bioactive elements and the methods used for assessment of their in vitro angiogenic potential is presented. The findings show that silicon and strontium can effectively enhance osseointegration through the simultaneous promotion of both angiogenesis and osteogenesis. Therefore, their integration onto the surface of biomaterials can ultimately decrease the incidence of implant failure due to aseptic loosening.Biomaterials & Tissue Biomechanic

Immunomodulation of surface biofunctionalized 3D printed porous titanium implants

Additive manufacturing (AM) techniques have provided many opportunities for the rational design of porous metallic biomaterials with complex and precisely controlled topologies that give rise to unprecedented combinations of mechanical, physical, and biological properties. These favorable properties can be enhanced by surface biofunctionalization to enable full tissue regeneration and minimize the risk of implant-associated infections (IAIs). There is, however, an increasing need to investigate the immune responses triggered by surface biofunctionalized AM porous metals. Here, we studied the immunomodulatory effects of AM porous titanium (Ti-6Al-4V) printed using selective laser melting and of two additional groups consisting of AM implants surface biofunctionalized using plasma electrolytic oxidation (PEO) with/without silver nanoparticles. The responses of human primary macrophages and human mesenchymal stromal cells (hMSCs) were studied in terms of cell viability, cell morphology and biomarkers of macrophage polarization. Non-treated AM porous titanium triggered a strong pro-inflammatory response in macrophages, albeit combined with signs of anti-inflammatory effects. The PEO treatment of AM porous titanium implants showed a higher potential to induce polarization towards a pro-repair macrophage phenotype. We detected no cytotoxicity against hMSCs in any of the groups. However, the incorporation of silver nanoparticles resulted in strong cytotoxicity against attached macrophages. The results of this study indicate the potential immunomodulatory effects of the AM porous titanium enhanced with PEO treatment, and point towards caution and further research when using silver nanoparticles for preventing IAIs.ChemE/Product and Process EngineeringBiomaterials & Tissue Biomechanic