Nanoscale surface modifications of medically relevant metals: state-of-the art and perspectives

Evidence that nanoscale surface properties stimulate and guide various molecular and biological processes at the implant/tissue interface is fostering a new trend in designing implantable metals. Cutting-edge expertise and techniques drawn from widely separated fields, such as nanotechnology, materials engineering and biology, have been advantageously exploited to nanoengineer surfaces in ways that control and direct these processes in predictable manners. In this review, we present and discuss the state-of-the-art of nanotechnology-based approaches currently adopted to modify the surface of metals used for orthopedic and dental applications, and also briefly consider their use in the cardiovascular field. The effects of nanoengineered surfaces on various in vitro molecular and cellular events are firstly discussed. This review also provides an overview of in vivo and clinical studies with nanostructured metallic implants, and addresses the potential influence of nanotopography on biomechanical events at interfaces. Ultimately, the objective of this work is to give the readership a comprehensive picture of the current advances, future developments and challenges in the application of the infinitesimally small to biomedical surface science. We believe that an integrated understanding of the in vitro and particularly of the in vivo behavior is mandatory for the proper exploitation of nanostructured implantable metals and, indeed, of all biomaterials.     

Developing pyrrole-derived antimycobacterial agents: a rational lead optimization approach

Tuberculosis (TB) represents a never-ending challenge toward which research efforts are needed. Drug resistance is the key problem that scientists in the field need to fight. The development of new drugs endowed with novel modes of action against different biological targets is of extreme importance; these new agents should also exhibit lower toxicity compared with the anti-TB drugs currently available. Furthermore, new drugs should be inexpensive since most of the TB-infected population lives in developing nations. In the last few years, numerous researchers have focused their attention on TB, leading to the discovery of some interesting compounds. Among these, the pyrrole-derived compounds we developed can be considered very promising antimycobacterial agents. Aided by molecular modeling studies, we synthesized numerous compounds characterized by the same 1,5-diarylpyrrole scaffold and elucidated very interesting antitubercular/antimycobacterial properties. Some compounds identified are extremely promising and represent a step towards the design of novel lead structures in the fight against TB. Our efforts to this end are reviewed here.     

Color changes due to thermal ageing and artificial weathering of pigmented and textured ABS

Acrylonitrile–butadiene–styrene copolymers (ABS) are known to be sensitive towards ageing which can lead to color changes, primary interest in this study. The color changes were expressed in terms of the CIELAB color system. ABS plaques were subjected to heat ageing and artificial weathering. Uncolored ABS and dark gray colored specimens were employed. The pigmented ABS plaques were also imposed with different surface textures. In general, the uncolored material suffered from the most severe discoloration and the artificial weathering produced the strongest effect. For both types of specimens, a clear yellowing took place. Both the pigment system and the surface texture affected the color development during the ageing test. The latter can be of significant importance in certain applications when components with different surface textures are placed adjacent to each other. The surface micro‐hardness increased with increasing ageing time and its change followed that of the discoloration. Chemical changes of the surface layers were characterized by FTIR and were in accordance with results reported in the literature; i.e., an increase of the bands associated with carbonyl groups with increasing ageing time and a decrease of the bands associated with the polybutadiene phase clearly indicated chemical degradation due to ageing treatments. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers     

OPTIMAL KINETIC PARAMETERS AND BATCH MODELING FOR PECTIN HYDROLYSIS TO GALACTURONIC ACID WITH PECTINEX ULTRA SP-L ENZYME

Galacturonic acid is a monosaccharide obtained by pectin hydrolysis and a suitable substrate to produce bioethanol by fermentation. This article focuses on quantification of citrus pectin hydrolysis to galacturonic acid and provides new, reliable kinetic parameters for the Michaelis-Menten equation when the well-known commercial Pectinex Ultra SP-L is employed as enzyme. They are: r _max  = 1.10 g/(L min), K _m  = 10.42 g/L, and K _IGA  = 10.05 g/L, as obtained with a great accuracy by a nonlinear regression method and confirmed by the three classical linearization procedures (Lineweaver-Burk, Langmuir, and Eadie-Hofstee). The quantification of product inhibition has been achieved, with its inclusion in the rate equation. A batch reactor model yields perfect agreement between predictions and experiments, even under conditions different from those on which the parameters had been determined by regression.     

Synthesis and characterization of new poly(arylene ether 1,3,4-oxadiazole)s based on dihydroxynaphthalene isomers

Summary A series of new poly(arylene ether 1,3,4-oxadiazole)s has been obtained starting from a difluorosubstituted monomer containing 1,3,4-oxadiazole rings and some dihydroxynaphthalene isomers. The polymers have been prepared by polycondensation in solution and have been obtained in quantitative yield. They had inherent viscosity from 0.2 to 0.82 dL/g, showed good thermal stability (10% weight loss temperatures in nitrogen and air were above 460 and 450°C, respectively) and high glass transition temperatures (in the range of 197–232°C). The polymers were characterized by elemental and infrared analyses, GPC and wide angle X-ray diffraction. Received: 27 June 2000/Revised version: 2 October 2000/Accepted: 2 October 2000     

Influence of Nano,Micro, and Macro Topography of Dental Implant Surfaces on Human Gingival Fibroblasts

Current research on dental implants has mainly focused on the influence of surface roughness on the rate of osseointegration, while studies on the development of surfaces to also improve the interaction of peri-implant soft tissues are lacking. To this end, the first purpose of this study was to evaluate the response of human gingival fibroblasts (hGDFs) to titanium implant discs (Implacil De Bortoli, Brazil) having different micro and nano-topography: machined (Ti-M) versus sandblasted/double-etched (Ti-S). The secondary aim was to investigate the effect of the macrogeometry of the discs on cells: linear-like (Ti-L) versus wave-like (Ti-W) surfaces. The atomic force microscopy (AFM) and scanning electron microscopy (SEM) analysis showed that the Ti-S surfaces were characterized by a significantly higher micro and nano roughness and showed the 3D macrotopography of Ti-L and Ti-W surfaces. For in vitro analyses, the hGDFs were seeded into titanium discs and analyzed at 1, 3, and 5 days for adhesion and morphology (SEM) viability and proliferation (Cck-8 and MTT assays). The results showed that all tested surfaces were not cytotoxic for the hGDFs, rather the nano-micro and macro topography favored their proliferation in a time-dependent manner. Especially, at 3 and 5 days, the number of cells on Ti-L was higher than on other surfaces, including Ti-W surfaces. In conclusion, although further studies are needed, our in vitro data proved that the use of implant discs with Ti-S surfaces promotes the adhesion and proliferation of gingival fibroblasts, suggesting their use for in vivo applications.     

Early Osteogenic Marker Expression in hMSCs Cultured onto Acid Etching-Derived Micro- and Nanotopography 3D-Printed Titanium Surfaces

Polyetheretherketone (PEEK) titanium composite (PTC) is a novel interbody fusion device that combines a PEEK core with titanium alloy (Ti6Al4V) endplates. The present study aimed to investigate the in vitro biological reactivity of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) to micro- and nanotopographies produced by an acid-etching process on the surface of 3D-printed PTC endplates. Optical profilometer and scanning electron microscopy were used to assess the surface roughness and identify the nano-features of etched or unetched PTC endplates, respectively. The viability, morphology and the expression of specific osteogenic markers were examined after 7 days of culture in the seeded cells. Haralick texture analysis was carried out on the unseeded endplates to correlate surface texture features to the biological data. The acid-etching process modified the surface roughness of the 3D-printed PTC endplates, creating micro- and nano-scale structures that significantly contributed to sustaining the viability of hBM-MSCs and triggering the expression of early osteogenic markers, such as alkaline phosphatase activity and bone-ECM protein production. Finally, the topography of 3D-printed PTC endplates influenced Haralick’s features, which in turn correlated with the expression of two osteogenic markers, osteopontin and osteocalcin. Overall, these data demonstrate that the acid-etching process of PTC endplates created a favourable environment for osteogenic differentiation of hBM-MSCs and may potentially have clinical benefit.     

Eco-Sustainable Silk Fibroin/Pomegranate Peel Extract Film as an Innovative Green Material for Skin Repair

Skin disorders are widespread around the world, affecting people of all ages, and oxidative stress represents one of the main causes of alteration in the normal physiological parameters of skin cells. In this work, we combined a natural protein, fibroin, with antioxidant compounds extracted in water from pomegranate waste. We demonstrate the effective and facile fabrication of bioactive and eco-sustainable films of potential interest for skin repair. The blended films are visually transparent (around 90%); flexible; stable in physiological conditions and in the presence of trypsin for 12 days; able to release the bioactive compounds in a controlled manner; based on Fickian diffusion; and biocompatible towards the main skin cells, keratinocytes and fibroblasts. Furthermore, reactive oxygen species (ROS) production tests demonstrated the high capacity of our films to reduce the oxidative stress induced in cells, which is responsible for various skin diseases.     

Supplementation with SCFAs Re-Establishes Microbiota Composition and Attenuates Hyperalgesia and Pain in a Mouse Model of NTG-Induced Migraine

Migraine is a common brain-disorder that affects 15% of the population. Converging evidence shows that migraine is associated with gastrointestinal disorders. However, the mechanisms underlying the interaction between the gut and brain in patients with migraine are not clear. In this study, we evaluated the role of the short-chain fatty acids (SCFAs) as sodium propionate (SP) and sodium butyrate (SB) on microbiota profile and intestinal permeability in a mouse model of migraine induced by nitroglycerine (NTG). The mice were orally administered SB and SP at the dose of 10, 30 and 100 mg/kg, 5 min after NTG intraperitoneal injections. Behavioral tests were used to evaluate migraine-like pain. Histological and molecular analyses were performed on the intestine. The composition of the intestinal microbiota was extracted from frozen fecal samples and sequenced with an Illumina MiSeq System. Our results demonstrated that the SP and SB treatments attenuated hyperalgesia and pain following NTG injection. Moreover, SP and SB reduced histological damage in the intestine and restored intestinal permeability and the intestinal microbiota profile. These results provide corroborating evidence that SB and SP exert a protective effect on central sensitization induced by NTG through a modulation of intestinal microbiota, suggesting the potential application of SCFAs as novel supportive therapies for intestinal disfunction associated with migraine.