Bacterial infections represent nowadays the major reason of biomaterials implant failure, however, most of the available implantable materials do not hold antimicrobial properties, thus requiring ...antibiotic therapy once the infection occurs. The fast raising of antibiotic-resistant pathogens is making this approach as not more effective, leading to the only solution of device removal and causing devastating consequences for patients. Accordingly, there is a large research about alternative strategies based on the employment of materials holding intrinsic antibacterial properties in order to prevent infections. Between these new strategies, new technologies involving the use of carbon-based materials such as carbon nanotubes, fullerene, graphene and diamond-like carbon shown very promising results. In particular, graphene- and graphene-derived materials (GMs) demonstrated a broad range antibacterial activity toward bacteria, fungi and viruses. These antibacterial activities are attributed mainly to the direct physicochemical interaction between GMs and bacteria that cause a deadly deterioration of cellular components, principally proteins, lipids, and nucleic acids. In fact, GMs hold a high affinity to the membrane proteoglycans where they accumulate leading to membrane damages; similarly, after internalization they can interact with bacteria RNA/DNA hydrogen groups interrupting the replicative stage. Moreover, GMs can indirectly determine bacterial death by activating the inflammatory cascade due to active species generation after entering in the physiological environment. On the opposite, despite these bacteria-targeted activities, GMs have been successfully employed as pro-regenerative materials to favor tissue healing for different tissue engineering purposes. Taken into account these GMs biological properties, this review aims at explaining the antibacterial mechanisms underlying graphene as a promising material applicable in biomedical devices.
Functional ability is the basis of healthy aging. Articular cartilage degeneration is amongst the most prevalent degenerative conditions that cause adverse impacts on the quality of life; moreover, ...it represents a key predisposing factor to osteoarthritis (OA). Both the poor capacity of articular cartilage for self-repair and the unsatisfactory outcomes of available clinical interventions make innovative tissue engineering a promising therapeutic strategy for articular cartilage repair. Significant progress was made in this field; however, a marked heterogeneity in the applied biomaterials, biofabrication, and assessments is nowadays evident by the huge number of research studies published to date. Accordingly, this literature review assimilates the most recent advances in cell-based and cell-free tissue engineering of articular cartilage and also focuses on the assessments performed via various in vitro studies, ex vivo models, preclinical in vivo animal models, and clinical studies in order to provide a broad overview of the latest findings and clinical translation in the context of degenerated articular cartilage and OA.
Abstract
In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped ...with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a ~ 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a ~ 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic pro-osteogenic effect of combined physical stimulations.
Boswellia serrata Roxb. extract (BSE), rich in boswellic acids, is well known as a potent anti-inflammatory natural drug. However, due to its limited aqueous solubility, BSE inclusion into an ...appropriate carrier, capable of improving its release in the biological target, would be highly desirable. Starting with this requirement, new hybrid composites based on the inclusion of BSE in a lamellar solid layered double hydroxide (LDH), i.e., magnesium aluminum carbonate, were developed and characterized in the present work. The adopted LDH exhibited a layered crystal structure, comprising positively charged hydroxide layers and interlayers composed of carbonate anions and water molecules; thus, it was expected to embed negatively charged boswellic acids. In the present case, a calcination process was also adopted on the LDH to increase organic acid loading, based on the replacement of the original inorganic anions. An accurate investigation was carried out by TGA, PXRD, FT-IR/ATR, XPS, SEM, and LC-MS to ascertain the nature, interaction, and quantification of the active molecules of the vegetal extract loaded in the developed hybrid materials. As a result, the significant disruption of the original layered structure was observed in the LDH subjected to calcination (LDHc), and this material was able to include a higher amount of organic acids when its composite with BSE was prepared. However, in vitro tests on the composites’ bioactivity, expressed in terms of antimicrobial and anti-inflammatory activity, evidenced LDH–BSE as a better material compared to BSE and to LDHc–BSE, thus suggesting that, although the embedded organic acid amount was lower, they could be more available since they were not firmly bound to the clay. The composite was able to significantly decrease the number of viable pathogens such as Escherichia coli and Staphylococcus aureus, as well as the internalization of toxic active species into human cells imposing oxidative stress, in comparison to the BSE.
Stainless steel implants are suitable candidates for bone replacement due to their cytocompatibility and mechanical resistance, but they suffer from lack of bioactivity and are prone to bacterial ...infections. Accordingly, to overcome those limitations, in this study we developed by electrophoretic deposition (EPD), an innovative surface coating made of (i) zein, a natural fibroblast-friendly polymer, (ii) bioactive glass, a pro-osteogenic inorganic material and (iii) copper containing bioactive glass, an antibacterial and pro-angiogenic material. FESEM images confirmed that porous, uniform and free of cracks coatings were obtained by EPD; moreover, coatings were resistant to mechanical stress as demonstrated by the tape test, resulting in a 4B classification of adhesion to the substrate. The coatings were cytocompatible as indicated by metabolism evaluation of human fibroblasts, endothelial cells and mature or progenitor osteoblasts cultivated in direct contact with the specimens. They also maintained pro-osteogenic properties towards undifferentiated progenitor cells that expressed osteogenic genes after 15 days of direct cultivation. Copper conferred antibacterial properties as biofilm formation of the joint pathogens Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli was significantly reduced in comparison with copper-free coatings (p < 0.05). Moreover, this anti-infective activity resulted as targeted towards bacteria while the cells viability was preserved when cells and bacteria were cultivated in the same environment by a co-culture assay. Finally, copper ability to recruit blood vessels and to inhibit bacterial infection was confirmed in vivo where the growth of S. aureus biofilm was inhibited and the formation of new (<50 μm diameter spread) blood vessels was observed.
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•Zein and copper doped bioactive glass combined in composite coating.•Coating was compatible with fibroblast, osteoblast progenitor and endothelial cells.•Copper was strongly antibacterial towards joint pathogens.•Copper promoted angiogenesis in vivo.
It is widely recognized that surface nanotextures applied on a biomaterial can affect wettability, protein absorption and cellular and/or bacterial adhesion; accordingly, they are nowadays of great ...interest to promote fast osseointegration and to maintain physiological healing around biomedical implants. In order to be suitable for clinical applications, surface nanotextures must be not only safe and effective, but also, they should be produced through industrial processes scalable to real devices with sustainable processes and costs: this is often a barrier to the market entry. Based on these premises, a chemical surface treatment designed for titanium and its alloys able to produce an oxide layer with a peculiar sponge like nanotexture coupled with high density of hydroxyl group is here presented. The modified Ti-based surfaces previously showed inorganic bioactivity intended as the ability to induce apatite precipitation in simulated body fluid. Physicochemical properties and morphology of the obtained layers have been characterized by means of FESEM, XPS, and Zeta-potential. Biological response to osteoblasts progenitors and bacteria has been tested. The here proposed nanotextured surfaces successfully supported osteoblasts progenitors' adhesion, proliferation and extracellular matrix deposition thus demonstrating good biocompatibility. Moreover, the nanotexture was able to significantly reduce bacteria surface colonization when the orthopedic and the periodontal pathogens
and
strains were applied for a short time. Finally, the applicability of the proposed surface treatment to real biomedical devices (a 3D acetabular cup, a dental screw and a micro-sphered laryngeal implant) has been here demonstrated.
To promote osteointegration and simultaneously limit bacterial contamination without using antibiotics, we designed innovative composite cements containing copper (Cu)-doped bioactive glass powders. ...Cu-doped glass powders were produced by a melt and quenching process, followed by an ion-exchange process in a Cu salt aqueous solution. Cu-doped glass was incorporated into commercial polymethyl methacrylate (PMMA)-based cements with different viscosities. The realized composites were characterized in terms of morphology, composition, leaching ability, bioactivity, mechanical, and antibacterial properties. Glass powders appeared well distributed and exposed on the PMMA surface. Composite cements showed good bioactivity, evidencing hydroxyapatite precipitation on the sample surfaces after seven days of immersion in simulated body fluid. The leaching test demonstrated that composite cements released a significant amount of copper, with a noticeable antibacterial effect toward
strain. Thus, the proposed materials represent an innovative and multifunctional tool for orthopedic prostheses fixation, temporary prostheses, and spinal surgery.
Air-polishing with low abrasiveness powders is fast arising as a valid and mini-invasive instrument for the management of biofilm colonizing dental implants. In general, the reported advantage is the ...efficient removal of plaque with respect to the titanium integrity. In the present study, we evaluated the in situ plaque removal and the preventive efficacy in forestalling further infection of an innovative erythritol/chlorhexidine air-polishing powder and compared it with sodium bicarbonate. Accordingly, two peri-implantitis-linked biofilm formers, strains
and
, were selected and used to infect titanium disks before and after the air-polishing treatment to test its ability in biofilm removal and re-colonization inhibition, respectively. Biofilm cell numbers and viability were assayed by colony-forming unit (CFU) count and metabolic-colorimetric (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2
-Tetrazolium-5-Carboxanilide) (XTT) assay. Results demonstrated that air-polishing performed with either sodium bicarbonate or erythritol/chlorhexidine was effective in reducing bacteria biofilm viability and number on pre-infected specimens, thus showing a similar ability in counteracting existing infection in situ; on the other hand, when air-polished pre-treated disks were infected, only erythritol/chlorhexidine powder showed higher post-treatment biofilm re-growth inhibition. Finally, surface analysis via mechanical profilometry failed to show an increase in titanium roughness, regardless of the powder selected, thus excluding any possible surface damage due to the use of either sodium bicarbonate or erythritol/chlorhexidine.
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