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To design, develop and study a novel drug delivery system for intraocular applications. The spin coating technique was applied to develop a polymeric, drug‐eluting thin film consisting of a blend of organic polymers [poly (D, L lactide coglycolide) lactide: glycolide 75: 25, PLGA and polycaprolactone, PCL] and dexamethasone on the surface of intraocular lenses (IOLs). The initial durability of the IOLs during spinning was assessed. Information about the structural and optical properties of the modified IOLs was extracted using atomic force microscopy, scanning electron microscopy and spectroscopic ellipsometry. A drug release study was conducted for 8 weeks. The IOLs were durable in spinning speeds higher than the ones used to develop thin films. Single‐layer thin films were successfully developed on the optics and the haptics of the lenses. The films formed nanopores with encapsulated aggregates of dexamethasone. The spectroscopic ellipsometry showed an acceptable optical transparency of the lenses regardless of the deposition of the drug‐eluting films on their surface. The drug release study demonstrated gradual dexamethasone release over the selected period. In conclusion, the novel drug‐eluting IOL system exhibited desired properties regarding its transparency and drug release rate. Further research is necessary to assess their suitability as an intraocular drug delivery system.

Background Cataract surgery is a very popular operation that requires a postoperative period of frequent instillation of antibiotic and anti-inflammatory eye drops. Modified drug-eluting intraocular lenses (IOLs) may eliminate the need for eye drops after surgery. Aim The purpose of this study is to compare the morphological characteristics of dexamethasone eluting biodegradable polymeric thin films developed on the surface of commercially available IOLs by three different methods. Method This experimental study was conducted between May and August of 2021 in the Lab for Thin Films - Nanobiomaterials - Nanosystems & Nanometrology (LTFN) of the Aristotle University of Thessaloniki. A mixture of two organic polymers [Poly (D, L-lactide-co-glycolide)(PLGA), lactide: glycolide (75:25) and Polycaprolactone (PCL)] and dexamethasone was prepared and then deposited on the surface of three-piece IOLs by spin coating, by spray coating, and by gravure printing. The modified IOLs were sterilized with the use of ultraviolet (UV) radiation and plasma treatment. Their structural properties were studied with the use of atomic force microscopy (AFM). Results Spin coating and gravure printing produced uniform thin films on the surface of the IOLs which were not damaged during the sterilization process. Spray coating led to the partial coating of the surface of the IOLs; the thin films underwent alterations following plasma treatment. Conclusions Thin films developed by spin coating and gravure printing on IOLs demonstrate the desired morphological characteristics that make them suitable candidates for further research.

Cardiovascular diseases constitute a major public health concern in industrialized nations. Oxidative stress induced free radicals play a critical role in cellular processes implicated in atherosclerosis and many other heart diseases. Quercetin (Qu) is an antioxidant drug which is shown that effectively protects against cardiovascular diseases (CVDs). Encapsulation of drugs in polymeric NPs are widely used in producing sustained and controllable drug release, or to avoid degradation of non-released drugs. In this current work, a novel system of polymeric PLGA NPs loaded with Qu, was fabricated via electrohydrodynamic atomization process (EHDA) in order to improve poor aqueous solubility and stability of the drug with the aim of preventing atherosclerosis. The fabricated nanoparticles collected in a stable glass substrate. The results of atomic force microscopy (AFM) analysis and the scanning electron microscope (SEM), confirmed the fabrication of spherical polymeric nanoparticles with diameter ranging from 300nm to350 nm, narrow size distribution and smooth surface. The release profile of quercetin from the particles was investigated by determining the drug amount released at specific intervals for by luminescence. Furthermore, XRD analysis was used to determine the physical status of Qu encapsulated in NPs compared with that of pure Qu. The information obtained from this study facilitates the design and fabrication of polymeric nanoparticles as possible delivery systems for encapsulation, protection and controlled release of the flavonoid quercetin which is aiming to protect against CVDs.

Milka Janjic,1,2 Foteini Pappa,1 Varvara Karagkiozaki,1 Christakis Gitas,2 Kiriakos Ktenidis,2 Stergios Logothetidis1 1Department of Physics, Laboratory for Thin Films – Nanosystems and Nanometrology, University of Thessaloniki, 2School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract: This study describes the development of drug-loaded nanofibrous scaffolds as a nanocoating for endovascular stents for the local and sustained delivery of rosuvastatin (Ros) and heparin (Hep) to injured artery walls after endovascular procedures via the electrospinning process.Purpose: The proposed hybrid covered stents can promote re-endothelialization; improve endothelial function; reduce inflammatory reaction; inhibit neointimal hyperplasia of the injured artery wall, due to well-known pleiotropic actions of Ros; and prevent adverse events such as in-stent restenosis (ISR) and stent thrombosis (ST), through the antithrombotic action of Hep.Methods: Biodegradable nanofibers were prepared by dissolving cellulose acetate (AC) and Ros in N,N-dimethylacetamide (DMAc) and acetone-based solvents. The polymeric solution was electrospun (e-spun) into drug-loaded AC nanofibers onto three different commercially available stents (Co–Cr stent, Ni–Ti stent, and stainless steel stent), resulting in nonwoven matrices of submicron-sized fibers. Accordingly, Hep solution was further used for fibrous coating onto the engineered Ros-loaded stent. The functional encapsulation of Ros and Hep drugs into polymeric scaffolds further underwent physicochemical analysis. Morphological characterization took place via scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses, while scaffolds’ wettability properties were obtained by contact angle (CA) measurements.Results: The morphology of the drug-loaded AC nanofibers was smooth, with an average diameter of 200–800nm, and after CA measurement, we concluded to the superhydrophobic nature of the engineered scaffolds. In vitro release rates of the pharmaceutical drugs were determined using a high-performance liquid chromatography assay, which showed that after the initial burst, drug release was controlled slowly by the degradation of the polymeric materials.Conclusion: These results imply that AC nanofibers encapsulated with Ros and Hep drugs have great potential in the development of endovascular grafts with anti-thrombogenic properties that can accelerate the re-endothelialization, reduce the neointimal hyperplasia and inflammatory reaction, and improve the endothelial function. Keywords: cardiovascular disease, stent, drug delivery, scaffolds, nanocoating

The number of patients in need of orthopaedic implants has increased rapidly over the past few years. Implant associated infections that are created after an invasive orthopaedic surgery are one of the major causes of implant failure. In this work, a drug delivery nano platform system was fabricated, consisted of Polycaprolactone (PCL) scaffolds loaded with the antibiotic drug vancomycin via Electrospinning process. Titanium implants’ surface has been modified with non-woven fibrous coatings while the efficacy and toxicity on fibroblasts were investigated in vitro. Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM) measurements showed the successful fabrication of those structures. Cytotoxicity studies took place in order to examine the cytocompatibilty of the nanoplatform. MTT assay and methylene blue staining showed an excellent cell adhesion and proliferation, thus enhance the cytocompatible behavior in vitro. Drug release kinetics further took place in line with degradation studies in order to evaluate the mass loss of polymers. This drug delivery nano platform is a promising nanovehicle to prevent and treat orthopedic implant-associated infections along with a simultaneously release of the drug in a controllable and sustainable manner.

Bacterial infections are a leading cause of death for millions of people worldwide, while few antibiotics have been proved effective against multidrug-resistant bacteria. Recently, nanoparticles have been used for the delivery of therapeutic agents to reduce bacterial infections due to their antimicrobial activity and unique mode of action. In our studies, silver nanoparticles (Ag NPs) have been used in order to meddle with associated infections for orthopaedic applications, due to their unique morphology and size. Nanoprecipitation method was used for the development of the NPs, using PVP (polyvinylpyrrolidone) as a reducing agent. Chitosan was used as a stabilizing and a coating agent at different concentrations (0.1%, 0.01% and 0.001%) in order to evaluate the most optimum capped coating. Atomic Force Microscopy (AFM) was the appropriate indicator for the morphological and topography analysis. Results showed that chitosan-capped NPs with 0.01% were found to be the most optimum. Transmittance measurements at plasmon emission at ∼320nm wavelength have showed Ag nanoparticles which were identified due to the sharp absorption peak. Variations of the absolute transmittance values due to the different thickness of the samples confirmed the coating of chitosan in Ag NPs. XRD measurements further took place and successfully have indicated the presence of chitosan in Ag nanoparticles’ surface. Electrospinning System was used for the formation of PCL (poly-e-caprolactone) scaffolds where Ag NPs were deposited via Electrospraying System. The final scaffolds were then studied with AFM and SEM (Scanning Electron Microscopy) Images. As a conclusion, the fabricated Ag NPs into polymer scaffolds appeared to be a valuable tool with antibacterial properties towards implant-associated orthopedic infections.

To study the development, characterisation, and drug release of one‐ and two‐layered thin films based on organic polymers [poly(D,L‐lactide‐co ‐glycolide) lactide:glycolide (65:35), poly(D,L‐lactide‐co ‐glycolide) lactide:glycolide (75:25), and polycaprolactone] and dexamethasone. To examine their applicability for intraocular lenses (IOLs) and function in intraocular drug delivery systems. Four series of thin films, single and double‐layer, were prepared by the spin‐coating method on a silicon substrate. The films were studied using atomic force microscopy and spectroscopic ellipsometry. The release rate of dexamethasone was studied for a period of ten weeks. Series A and C demonstrated the formation of large dexamethasone aggregates. The monolayer films of series C and D formed pores, in agreement with previous findings. The spectroscopic ellipsometry study demonstrated that the samples were transparent. The drug release study demonstrated that dexamethasone was released during the first 6 weeks at a desirable rate. The films exhibited properties suitable for use in intraocular drug delivery systems. The single‐layer thin films demonstrated a sufficient encapsulation of dexamethasone and appropriate release of the therapeutic substance. Further studies are necessary to investigate the possibility of developing the films directly on the surface of the IOL.

Electrospun nanofibrous scaffolds have been extensively used in several biomedical applications for tissue engineering due to their morphological resemblance to the extracellular matrix (ECM). Especially, there is a need for the cardiovascular implants to exhibit a nanostructured surface that mimics the native endothelium in order to promote endothelialization and to reduce the complications of thrombosis and implant failure. Thus, we herein fabricated poly-ε-caprolactone (PCL) electrospun nanofibrous scaffolds, to serve as coatings for cardiovascular implants and guide tissue regeneration. Oxygen plasma treatment was applied in order to modify the surface chemistry of the scaffold and its effect on cell attachment and growth was evaluated. The conditions of the surface modification were properly adjusted in order to define those conditions of the treatment that result in surfaces favorable for cell growth, while maintaining morphological integrity and mechanical behavior. Goniometry (contact angle measurements), scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS) measurements were used to evaluate the morphological and chemical changes induced by the plasma treatment. Moreover, depth-sensing nanoindentation was performed to study the resistance of the plasma-treated scaffolds to plastic deformation. Lastly, the cell studies indicated that all scaffolds were cytocompatible, with the plasma-treated ones expressing a more pronounced cell viability and adhesion. All the above findings demonstrate the great potential of these biomimetic tissue-engineering constructs as efficient coatings for enhanced compatibility of cardiovascular implants.

Thromboembolic diseases constitute a plague in our century, wherein an imbalance of hemostasis leads to thrombus formation and vessels constriction reducing blood flow. Hence, the recent rise of nanomedicine gives birth to advanced diagnostic modalities and therapeutic agents for the early diagnosis and treatment of such diseases. Multimodal nanoagents for the detection of intravascular thrombi and nanovehicles for thrombus-targeted fibrinolytic therapy are few paradigms of nanomedicine approaches to overcome current diagnostic treatment roadblocks and persistent clinical needs. This review highlights the nanomedicine strategies to improve the imaging and therapy of acute thrombi by nanoparticles and nanotheranostics, the detailed imaging of thrombogenic proteins and platelets via atomic force microscopy with the knowledge basis of thrombosis pathophysiology and nanotoxicity., Lay abstract: The present review highlights the perspectives of nanomedicine in enhancing the diagnostic and therapeutic strategies to deal with thrombosis. The basics in thrombosis are highlighted to provide the reader with better comprehension of the application of nanotools and various multimodal nanocarriers for diagnosis, targeted therapy and monitoring of the disease. The visualization and treatment of acute thrombi using multifunctional nanoparticles and nanotheranostics, along with the structural investigation of the blood-clotting proteins exploiting the atomic force microscopy capabilities are comprehensively described. At the same time, toxicity and biocompatibility issues regarding nanoparticles are discussed.

Varvara Karagkiozaki,1,2 Panagiotis G Karagiannidis,1 Nikolaos Kalfagiannis,1 Paraskevi Kavatzikidou,1 Panagiotis Patsalas,3 Despoina Georgiou,1 Stergios Logothetidis11Lab for Thin Films – Nanosystems and Nanometrology (LTFN), Physics Department, Aristotle University of Thessaloniki, Thessaloniki, 2AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, 3Department of Materials Science and Engineering, University of Ioannina, Ioannina, Epirus, GreeceBackground: Nanomedicine has the potential to revolutionize medicine and help clinicians to treat cardiovascular disease through the improvement of stents. Advanced nanomaterials and tools for monitoring cell–material interactions will aid in inhibiting stent thrombosis. Although titanium boron nitride (TiBN), titanium diboride, and carbon nanotube (CNT) thin films are emerging materials in the biomaterial field, the effect of their surface properties on platelet adhesion is relatively unexplored.Objective and methods: In this study, novel nanomaterials made of amorphous carbon, CNTs, titanium diboride, and TiBN were grown by vacuum deposition techniques to assess their role as potential stent coatings. Platelet response towards the nanostructured surfaces of the samples was analyzed in line with their physicochemical properties. As the stent skeleton is formed mainly of stainless steel, this material was used as reference material. Platelet adhesion studies were carried out by atomic force microscopy and scanning electron microscopy observations. A cell viability study was performed to assess the cytocompatibility of all thin film groups for 24 hours with a standard immortalized cell line.Results: The nanotopographic features of material surface, stoichiometry, and wetting properties were found to be significant factors in dictating platelet behavior and cell viability. The TiBN films with higher nitrogen contents were less thrombogenic compared with the biased carbon films and control. The carbon hybridization in carbon films and hydrophilicity, which were strongly dependent on the deposition process and its parameters, affected the thrombogenicity potential. The hydrophobic CNT materials with high nanoroughness exhibited less hemocompatibility in comparison with the other classes of materials. All the thin film groups exhibited good cytocompatibility, with the surface roughness and surface free energy influencing the viability of cells.Keywords: platelets, cell viability, titanium boron nitride, atomic force microscopy, carbon nanotubes

Cardiovascular stents are commonly used for the treatment of cardiovascular diseases that in developed societies are the most frequent causes of mortality and morbidity. In recent years, thorough research and development of drug-eluting stents has been done, with emphasis on coronary stenting to avoid the most common complication, in-stent thrombosis. Dipyridamole (DPM) is a medication that inhibits blood clot formation. Drug delivery nanoplatforms consisting of biodegradable polymers can be fabricated via electrospinning deposition, known for its cost-effective and versatile advantages, that produces fibrous scaffolds that are able to sustain and control drug release. A novel drug delivery nanosystem of polylactic acid fibrous scaffold loaded with the anti-platelet drug DPM was fabricated by electrospinning as coating for cardiovascular stents. The surface morphology and topography that were evaluated via atomic force microscopy, scanning electron microscopy and optical microscopy, were found to be good and suitable for tissue engineering. Contact angle measurements established the hydrophobic behavior of these fibrous nanoplatforms. Drug-release kinetics and degradation studies were conducted and revealed a sustained and controllable release of DPM, through this fibrous matrix over time. Finally, cytotoxicity studies took place to evaluate the cytocompatibility of the scaffold that confirmed its compatible behavior. The successful performance of this nanoplatform can lead to it being a valuable tool for atherosclerosis treatment.

Varvara C Karagkiozaki1,2, Stergios D Logothetidis2, Spyridon N Kassavetis2, George D Giannoglou11Aristotle University of Thessaloniki, Medical School, AHE PA University General Hospital, 1st Cardiology Department, Cardiovascular Engineering and Atherosclerosis Laboratory, Greece; 2Aristotle University of Thessaloniki, Physics Department, Laboratory for Thin Films – Nanosystems and Nanometrology (LTFN), GreeceAbstract: The treatment of patients with drug-eluting stents (DES) continues to evolve with the current emergence of DES technology that offers a combination of pharmacological and mechanical approaches to prevent arterial restenosis. However, despite the promising short-term and mid-term outcomes of DES, there are valid concerns about adverse clinical effects of late stent thrombosis. In this study, we present an example of how nanomedicine can offer solutions for improving stent coating manufacturing, by producing nanomaterials with tailored and controllable properties. The study is based on the exploitation of human platelets response towards carbon-based nanocoatings via atomic force microscope (AFM). AFM can facilitate the comprehensive analysis of platelets behavior onto stent nanocoatings and enable the study of thrombogenicity. Platelet-rich plasma from healthy donors was used for the real-time study of biointerfacial interactions. The carbon nanomaterials were developed by rf magnetron sputtering technique under controllable deposition conditions to provide favorable surface nanotopography. It was shown that by altering the surface topography of nanocoatings, the activation of platelets can be affected, while the carbon nanocoatings having higher surface roughness were found to be less thrombogenic in terms of platelets adhesion. This is an actual solution for improving the stent coating fabrication.Keywords: stents nanomedicine, carbon coating, atomic force microscopy platelets nanotechnology

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is among the most widely used polymers that are used as printed transparent electrodes for flexible Organic Electronic (OE) devices, such as Organic Photovoltaics (OPVs). The understanding of their optical properties and the correlation of the optical properties with their electronic properties and metallic-like behavior can lead to the optimization of their functionality as transparent electrodes in multilayer OE device architectures. In this work, we study the optical properties of different PEDOT:PSS formulations by non-destructive Spectroscopic Ellipsometry (SE), from the infrared to the far ultraviolet spectral regions. The optical response of PEDOT:PSS includes an intense optical absorption originated from the conductive part (PEDOT) at lower photon energies, whereas the electronic transition energies of the non-conductive PSS part have been measured at higher photon energies. Based on the different PEDOT:PSS formulations, the optical investigation revealed significant information on the relative contribution of conductive PEDOT and insulating PSS parts of the PEDOT:PSS formulation in the overall optical response, which can strongly impact the final device functionality and its optical transparency.

Varvara Karagkiozaki,1 Eleftherios Vavoulidis,1 Panagiotis G Karagiannidis,1 Maria Gioti,1 Dimitrios G Fatouros,2 Ioannis S Vizirianakis,3 Stergios Logothetidis11Lab for Thin Films–Nanosystems and Nanometrology, Physics Department, 2Department of Pharmaceutical Technology, 3Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, GreeceAbstract: Biodegradable polymers can be applied to a variety of implants for controlled and local drug delivery. The aim of this study is to develop a biodegradable and nanoporous polymeric platform for a wide spectrum of drug-eluting implants with special focus on stent-coating applications. It was synthesized by poly(DL-lactide-co-glycolide) (PLGA 65:35, PLGA 75:25) and polycaprolactone (PCL) in a multilayer configuration by means of a spin-coating technique. The antiplatelet drug dipyridamole was loaded into the surface nanopores of the platform. Surface characterization was made by atomic force microscopy (AFM) and spectroscopic ellipsometry (SE). Platelet adhesion and drug-release kinetic studies were then carried out. The study revealed that the multilayer films are highly nanoporous, whereas the single layers of PLGA are atomically smooth and spherulites are formed in PCL. Their nanoporosity (pore diameter, depth, density, surface roughness) can be tailored by tuning the growth parameters (eg, spinning speed, polymer concentration), essential for drug-delivery performance. The origin of pore formation may be attributed to the phase separation of polymer blends via the spinodal decomposition mechanism. SE studies revealed the structural characteristics, film thickness, and optical properties even of the single layers in the triple-layer construct, providing substantial information for drug loading and complement AFM findings. Platelet adhesion studies showed that the dipyridamole-loaded coatings inhibit platelet aggregation that is a prerequisite for clotting. Finally, the films exhibited sustained release profiles of dipyridamole over 70 days. These results indicate that the current multilayer phase therapeutic approach constitutes an effective drug-delivery platform for drug-eluting implants and especially for cardiovascular stent applications.Keywords: drug delivery, implants, stents, polymers, spin-coating, atomic force microscopy

Varvara Karagkiozaki1,2, Stergios Logothetidis1, Sylvie Lousinian1, George Giannoglou21Physics Department, Laboratory for Thin Films – Nanosystems and Nanometrology (LTFN); 2Medical School, AHEPA University General Hospital, 1st Cardiology Department, Aristotle University of Thessaloniki, GreeceAbstract: Electric surface properties of biomaterials, playing key role to various biointerfacial interactions, were related to hemocompatibility and biosensing phenomena. In this study, the examination of surface electric properties of amorphous hydrogenated carbon thin films (a-C:H) was carried out by means of electrostatic force microscope (EFM) and observation of differences in spatial charge distribution on the surface of the examined films during platelets adhesion was made. The thrombogenic potential of a-C:H thin films developed by agnetron sputtering with ∼42% sp3 content and hydrogen partial pressure during deposition was evaluated, by in situ observation with atomic force microscope (AFM) of platelets’ activation and their subsequent adhesion. Platelet-rich plasma drawn from healthy donors was used and semi-contact mode of AFM was applied. Platelets behavior and their correlation with the electric surface properties of the examined a-C:H films by EFM was made for hemocompatibility enhancement and sensing platelets that are less electrical negatively charged and with higher tendency to aggregate and form thrombus. The results are discussed in view of the effect of different deposition conditions of hydrogenated carbon films on their structural and morphological characteristics, surface roughness and electrical properties attributing to different hemocompatibility and sensing aspects.Keywords: amorphous hydrogenated carbon, platelets, thrombogenicity, atomic force microscopy, electric force microscopy, medical applications&nbsp