Theoretical modeling approach for adsorption of fibronectin on the nanotopographical implants

The success of orthopedic implants depends on the sufficient integration between tissue and implant, which is influenced by the cellular responses to their microenvironment. The conformation of adsorbed extracellular matrix is crucial for cellular behavior instruction via manipulating the physiochemical features of materials. To investigate the electrostatic adsorption mechanism of fibronectin on nanotopographies, a theoretical model was established to determine surface charge density and Coulomb’s force of nanotopography – fibronectin interactions using a Laplace equation satisfying the boundary conditions. Surface charge density distribution of nanotopographies with multiple random fibronectin was simulated based on random number and Monte Carlo hypothesis. The surface charge density on the nanotopographies was compared to the experimental measurements, to verify the effectiveness of the theoretical model. The model was implemented to calculate the Coulomb’s force generated by nanotopographies to compare the fibronectin adsorption. This model has revealed the multiple random quantitative fibronectin electrostatic adsorption to the nanotopographies, which is beneficial for orthopedic implant surface design. Significance: The conformation and distribution of adsorbed extracellular matrix on biomedical implants are crucial for directing cellular behaviors. However, the Ti nanotopography-ECM interaction mechanism remains largely unknown. This is mostly because of the interactions that are driven by electrostatic force, and any experimental probe could interfere with the electric field between the charged protein and Ti surface. A theoretical model is hereby proposed to simulate the adsorption between nanotopographies and fibronectin. Random number and Monte Carlo hypothesis were applied for multiple random fibronectin simulation, and the Coulomb’s force between nanoconvex and nanoconcave structures was comparatively analyzed

Stochastic Modeling of Biofilm Formation with Bacterial Quorum Sensing

Bacteria generally live in complicated structures called biofilms, consisting of communicating bacterial colonies and extracellular polymeric substance (EPS). Since biofilms are related to detrimental effects such as infection or antibiotic resistance in different settings, it is essential to model their formation. In this paper, a stochastic model is proposed for biofilm formation, using bacterial quorum sensing (QS). In this model, the biological processes in the biofilm formation are modeled as a chemical reaction network which includes bacterial reproduction, productions of autoinducer and EPS, and their diffusion. The modified explicit tau-leap simulation algorithm is adapted based on the two-state QS mechanism. Our approach is validated by using the experimental results of $\textit{Pseudomonas putida}$ IsoF bacteria for autoinducer and bacteria concentration. It is also shown that the percentage of EPS in the biofilm increases significantly after the state change in QS, while it decreases before QS is activated. The presented work shows how the biofilm growth can be modeled realistically by using the QS mechanism in stochastic simulations of chemical reactions.Comment: Submitted to ICC 202

Impact of lactoferrin on bone regenerative processes and its possible implementation in oral surgery - a systematic review of novel studies with metanalysis and metaregression

Background: Lactoferrin is an iron - binding glycoprotein with anti-inflammatory and anabolic properties found in many internal fluids. It is worth looking at novel studies, because of their methodology and observations that may once be applicable in modern implantology. The aim of the study is to answer the question if lactoferrin is a promising factor for bone regenerative process in oral surgery. Method: An electronic search was conducted on 14th October 2019 on the PubMed, Scopus and Web of Science databases. The keywords used in the search strategy were: lactoferrin AND bone regeneration AND oral surgery. The qualitative evaluation was conducted using the Jadad and Newcastle-Ottawa Quality Assessment Form. Then a metanalysis of a new bone growth and percentage of the resorbed graft were performed with the metaregression of lactoferrin dose to its outcome effects on bone regeneration. Results: The search strategy identified potential articles: 133 from PubMed, 2 from Scopus, 4 from Web of science. After removal of duplicates, 136 articles were analyzed. Subsequently, 131 papers were excluded because they did not meet the inclusion criteria. The remaining 5 papers were included in the qualitative synthesis. The use of lactoferrin clearly increases the growth of a newly formed bone (2.58, CI:[0.79, 4.37]), as well as shortens the time of the graft resorption (- 1.70, Cl:[3.43, 0.03]) and replaces it with a species-specific bone. Heterogeneity is significant at p < 0.001 level. Metaregression indicates that one unit increase in the log (Treatment dose), i.e. a 2.78 times increase of the Treatment dose, results in an increase of the Effect size by 0.682. Conclusions: The use of lactoferrin both systemically and locally promotes anabolic processes (new bone formation). There is a relationship between the increase in administered dose of lactoferrin and the intensity of new bone formation. However, it is not only necessary to continue experimental research, but also to extend it to the clinical studies on patients, due to the limitations of different animal model research and different methodology, to introduce lactoferrin as a standard procedure for the treatment of bone defects, because it is a promising product

Digital image correlation in dental materials and related research: A review

OBJECTIVE: Digital image correlation (DIC) is a non-contact image processing technique for full-field strain measurement. Although DIC has been widely used in engineering and biomechanical fields, it is in the spotlight only recently in dental materials. Therefore, the purpose of this review paper is introducing the working principle of the DIC technique with some modifications and providing further potential applications in various dental materials and related fields. METHODS: The accuracy of the algorithm depending on the environmental characteristics of the DIC technique, as well as the advantages and disadvantages of strain measurement using optical measurements, have been elaborated in dental materials and related fields. Applications to those researches have been classified into the following categories: shrinkage behavior of light-cured resin composite, resin-tooth interface, mechanical properties of tooth structure, crack extension and elastic properties of dental materials, and deformation of dental restoration and prosthesis. This classification and discussion were performed using literature survey and review based on numerous papers in the international journals published over the past 20 years. The future directions for predicting the precise deformation of dental materials under various environments, as well as limitations of the DIC technique, was presented in this review. RESULTS: The DIC technique was demonstrated as a more effective tool to measure full-field polymerization shrinkage of composite resin, even in a simulated clinical condition over the existing methods. Moreover, the DIC combined with other technologies can be useful to evaluate the mechanical behavior of material-tooth interface, dentine structure and restorative and prosthetic materials with high accuracy. Three-dimensional DIC using two cameras extended the measurement range in-plane to out-of-plane, enabling measure of the strain directly on the surface of dental restorations or prosthesis. SIGNIFICANCE: DIC technique is a potential tool for measuring and predicting the full-field deformation/strain of dental materials and actual prostheses in diverse clinical conditions. The versatility of DIC can replace the existing complex sensor devices in those studies

Bactericidal Surfaces: An Emerging 21st Century Ultra-Precision Manufacturing and Materials Puzzle

Progress made by materials scientists in recent years has greatly helped the field of ultra-precision manufacturing. Ranging from healthcare to electronics components, phenomena such as twinning, dislocation nucleation, and high-pressure phase transformation have helped to exploit plasticity across a wide range of metallic and semiconductor materials. One current problem at the forefront of the healthcare sector that can benefit from these advances is that of bacterial infections in implanted prosthetic devices. The treatment of implant infections is often complicated by the growth of bacterial biofilms on implant surfaces, which form a barrier that effectively protects the infecting organisms from host immune defenses and exogenous antibiotics. Further surgery is usually required to disrupt the biofilm, or to remove the implant altogether to permit antibiotics to clear the infection, incurring considerable cost and healthcare burdens. In this review, we focus on elucidating aspects of bactericidal surfaces inspired by the biological world to inform the design of implant surface treatments that will suppress bacterial colonization. Alongside manufacturing and materials related challenges, the review identifies the most promising natural bactericidal surfaces and provides representative models of their structure, highlighting the importance of the critical slope presented by these surfaces. The scalable production of these complex hierarchical structures on freeform metallic implant surfaces has remained a scientific challenge to date and, as identified by this review, is one of the many 21st-century puzzles to be addressed by the field of applied physics

Challenges of biofilm control and utilization : lessons from mathematical modelling

Funding This work was supported by a scholarship grant from the School of Natural and Computing Sciences at the University of Aberdeen and the Faculty of Health Sciences at Curtin University.Peer reviewedPostprin

Investigation of new formulations of acrylic bone cement containing antibiotics

Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2015Antibiotic-loaded bone cement (ALABC), is the common designation for polymethylmethacrylate bone cement (BC), used as drug-delivery system to prevent or to treat bone related-infections. Although presenting some disadvantages, the use of ALABC is still considered the standard of care for patients with chronic bone and joint infection, providing local delivery of high levels of antibiotics for an extended period without exceeding systemic toxicity, while being a more costeffective procedure when compared to cementless implants. Described and reported ALABCs drawbacks include the inadequate release of the loaded antibiotic, the lack of bioactivity and the poor diversity of antibiotics available in commercial premixed formulations. The base-concept of this study was to develop a novel ALABC with improved antibiotic release through the inclusion of particulate drug delivery systems and a release modulator without hampering the antibacterial activity of antibiotics or the BC mechanical and biocompatibility properties. Levofloxacin, a 3rd generation fluoroquinolone, and minocycline, a tetracycline, were the elected antibiotics to load into BC. The rationale behind this choice was related to their adequate microbiological and physicochemical characteristics. Both antibiotics present a broad-spectrum of activity against the main organisms responsible for bone and joint infections, namely Staphylococcus spp. Physicochemically, both are molecules with amphiphilic characteristics - greater for levofloxacin; soluble in acidic aqueous media; with high melting points (over 200ºC) and available in powder form; the latter two characteristics being restrictive when choosing for antibiotics to load into BC. Two main strategies were explored for the inclusion of antibiotics into particulate systems previous to incorporation into BC: 1) by encapsulation into PMMA; 2) by adsorption into calciumphosphate particles (CaPs). To improve drug release from the matrix, a pharmaceutical excipient was used as release modulator, lactose, and loaded into the BC powder component. A step-by-step approach was pursued: 1st. Assessment of antibiotics encapsulation into PMMA particles and of antibiotics in vitro release followed by loading antibiotic-loaded-particles into BC; The PMMA biopolymer was chosen to prepare PMMA-particles (PMMAp) foreseeing a mechanical reinforcement of the final ALABC matrix, because PMMA is the base-polymer of both systems. Plain, levofloxacin- and minocycline-loaded particles were successfully prepared using the double-emulsion solvent evaporation method. Since only minocycline-PMMAp registered an interesting in vitro release profile, studies proceeded with these particles and 15% (wparticles/wBC) were loaded into BC, which, on the other hand, hindered BC setting. 2nd. Effect of the inclusion of lactose into BC, monitoring antibiotics in vitro release, quasi-static mechanical properties and biocompatibility of the resultant matrices; Each powdered antibiotic was directly loaded into BC, and lactose, was added to each formulation. The amount of antibiotic loaded corresponded to the low-dose currently used in commercial ALABCs formulations - 2.5% (w/wBC) - in order to provide an effective antimicrobial activity and preserve the mechanical properties. As to lactose, 10% (wL/wBC) resulted in the optimised amount to be loaded into BC. This lactose-modified BC matrix allowed total release of the minocycline after a one-week period, and a 3.5-fold increase of levofloxacin release compared to control without lactose, over a 7-week period. 3rd. Inclusion of levofloxacin-adsorbed doped CaPs into BC and monitoring of the antibiotics in vitro release, quasi-static mechanical properties and biocompatibility of the resultant matrices; Intending to improve antibiotic release and bioactivity calcium-phosphate particles (CaPs) were tested as drug delivery system. Mg- and Sr-doped CaPs were prepared as levofloxacin carriers and were loaded into the 10% (wL/wBC) lactose-modified acrylic BC at 2.5% (wCaPs/wBC). This novel BC composite revealed a sustained release of levofloxacin over an 8-week period, with concentrations over the Staphylococcus spp. minimum inhibitory concentration values after 48 h. The novel 10% (wL/wBC) lactose-loaded ALABC, independently of the antibiotic or CaPs loaded, followed the same release mechanistic based on dissolution and subsequent diffusion of the antibiotic from the matrix. Both minocycline and levofloxacin maintained antibacterial activity against the Staphylococcus spp. after being released from ALABC matrix. Though this result suggest that polymerization setting did not affect these antibiotics, a novel in silico approach revealed the existence of covalent and non-covalent interactions between the levofloxacin and the BC matrix. Evaluation of the antibiotic-lactose-modified BC matrices regarding the quasi-static mechanical properties according to standard ISO 5833, clearly demonstrated that the mechanical performance was not compromised. Biocompatibility was also successfully evaluated following standard ISO 10993-5 with fibroblasts and osteoblasts cell lines incubated with extracts or in direct contact with BC composites, respectively. Results have shown that neither lactose nor the loaded antibiotics compromised the biocompatibility of the BC. All considered, these features justify the potential of lactose-loaded BC as a valuable step forward on the development of novel BC composites, namely with lactose, as release modulator, and doped CaP particles, as antibiotic carriers, for the control of bone and joint infections.Fundação para a Ciência e a Tecnologia (FCT), projetos, PEst-OE/SAU/UI4013/201

Fabrication and characterization of antibacterial surfaces derived from geranium essential oil using PECVD

Essential oils and plant extracts are rich sources of biologically-active compounds that can be used for manufacturing of antibacterial surfaces. This thesis reports the fabrication of pristine polymers, and zinc oxide/polymer films from geranium essential oil utilizing low power plasmaenhanced chemical vapor deposition technique (PECVD). The topographical, optical, mechanical, chemical, electrical and antibacterial properties of the fabricated films were in-depth studied. Geranium-derived polymer films were fabricated at various input RF power. The resultant polymer were founded to be optically transparent in the visibly region. The refractive index, extinction coefficient, and optical band gap were found to be not significantly dependent on the RF power. The crosslinking of the material increased with increasing input power. The topographical features appeared to be uniform, smooth, and pinhole free for all samples, and the surface roughness increased with an increase in the input power. Sample fabricated at 10 W demonstrated a remarkable reduction in the number of cells, biovolume, or biofilm thickness, while there was no significant difference in the bacterial growth between samples fabricated at 50 W and control. Zinc oxide nanoparticles were incorporated in the fabricated polymer films via a single-step approach that combines simultaneous plasma polymerization of geranium oil with thermal decomposition of zinc acetylacetonate Zn(acac)₂. The resultant nanocomposite thin films were systematically investigated. XPS survey proved the presence of ZnO in the matrix of formed polymers at 10 W and 50 W. SEM images demonstrated that the average size of ZnO nanoparticle slightly increased with an increase in the power of deposition from approximately 60 nm at 10 W to approximately 80 nm at 50 W. Confocal scanning laser microscopy images showed that viability of S. aureus and E.coli cells significantly reduced on surfaces of ZnO/composites compare to pristine polymers. The electrical properties of pristine and ZnO/composites thin films were investigated in metal– insulator–metal (MIM) structures. It was found that the capacitance of the films decreases at low frequencies (C ≈ 10⁻¹¹) and remains at a relatively constant value (C ≈ 10⁻¹⁰) at high frequencies. These films also have a low dielectric constant across a wide range of frequencies that decreases as the input RF power increases. The conductivity of pristine polymers was determined to be around 10⁻¹⁶–10⁻¹⁷ Ω⁻¹ m⁻¹, which is typical for insulating materials. Incorporation of ZnO nanoparticles into the polymer films did not change the nature of charge transport, as the nanocomposite films were found to behave as an insulator. However, the conductivity slightly of nanocomposite materials slightly improved measuring 10⁻¹⁴ Ω⁻¹ m⁻¹. Increasing the input power, along with introducing hydrogen gas to the plasma tube, produces desired sp2-bonded carbon nanostructures such as graphene materials. PECVD) had been utilized for the fabrication of high-quality vertically erected graphene nano-walls from geranium essential oil. The graphene synthesized using well-controllable system directly on silicon and quartz substrates without use any catalyst. SEM showed that the formed graphene had a length of few hundreds nanometers with thickness of 7 to 25 nm. AFM further confirmed the very sharp edges of the produced graphene. The material revealed relatively high water contact angle value ranging around 123˚. Antibacterial performance of graphene nano-walls was studied against grampositive and gram-negative microorganisms. Confocal scanning laser microscopy images demonstrated that the viability of E.coli and S. aureus cells were 32% and 38% were alive on graphene compare to controls, respectively

Cytotoxicity and Antibiofilm Activity of Silver-Polypropylene Nanocomposites

The development of biocompatible nanomaterials that interface with human skin and tissue is critical for advancing prosthetics and other therapeutic medical needs. In this perspective, the development of nanoparticles with cytotoxicity and antibiofilm properties and biocompatibility characteristics are important. Metallic silver (Ag) exhibits good biocompatibility, but it is often challenging to integrate it into a nanocomposite without compromising its antibiofilm properties for optimal applications. In this study, new polymer nanocomposites (PNCs) with ultra-low filling content (0.0023-0.046 wt%) of Ag nanoplates were manufactured and tested. The cytotoxicity and antibiofilm activity of different composites with polypropylene (PP) matrix were examined. At first, PNCs surface were analyzed by means of AFM (atomic force microscopy) with phase contrast evaluation and FTIR (Fourier-transform infrared spectroscopy) to study the Ag nanoplates distribution. Subsequently, the cytotoxicity and growth properties of biofilms were assessed by MTT assay protocol and detection of nitric oxide radicals. Antibacterial and antibiofilm activities were measured against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (K. pneumoniae). The PNCs with silver exhibited antibiofilm activity although they did not inhibit regular planktonic bacterial growth. Moreover, the PNCs were not cytotoxic to mammalian cells and did not induce significant immune response. These features reveal the potential of the PNCs developed in this study for usage in fabrication of prosthetics and other smart structures for biomedical applications.The work was made possible by an Internal Qatar University grant (IRCC-2022-563) and co-funded by University of Rome Tor Vergata. The statements made herein are solely the responsibility of the authors.Scopu