A functional hydrogel containing biopolymer microcarriers loaded with dexamethasone was developed to address the hearing loss that results from cisplatin ototoxicity. The drug delivery platform was tested both in vitro in the HEI-OC1 inner ear cell line and in vivo in a rat animal model. The newly described formula offered prolonged release of the contained dexamethasone for up to six days and transformed into a solid state at body temperature, thus counteracting its clearing through the Eustachian tube when injected into the middle ear. When tested in vitro, the inner ear cells exposed to cisplatin showed significantly higher viability at 48 hours when seeded on hydrogel containing dexamethasone-loaded microparticles than the cells treated with free dexamethasone. In the rat in vivo model, the ears of the rats treated with the hydrogel formulation presented better hearing thresholds after cisplatin administration than contralateral ears treated with free dexamethasone. The ears of the rats treated with microcarriers without inclusion in the functional hydrogel obtained better results than the dexamethasone treatment group but not as good as the hydrogel-containing microcarrier group. Histological assessment of the rats' inner ears showed better integrity of the structures and lower apoptosis in the microcarrier-treated groups than in the control group. Overall, the newly described microcarrier of dexamethasone offers better protection against cisplatin-induced hearing loss than free dexamethasone, especially when contained in a functional hydrogel formulation.

Understanding the effect of different electric potentials upon the preferential formation of biofilms inside microfluidic devices could represent a step forward in comprehending the mechanisms that govern biofilm formation and growth. 3D printed microfluidic devices were used to investigate the influence of the dielectrophoretic forces on the formation and growth of Staphylococcus aureus ATCC 25923 biofilms. Bacterial suspensions of 2.5 McF were pushed through microfluidic channels while simultaneously applying various potential differences between 10 and 60 V. The overall electric field distribution within the channel was simulated using the COMOSL software. The effect of the electric potential variation on the preferential biofilm formation was determined using an adjusted microtiter plate technique, as well as a qualitative method, Scanning Electron Microscopy (SEM). SEM images were used to describe the morphology of the biofilm surface. The conclusions show that the dielectrophoretic forces, resulting due to inhomogeneity of the electric field, have more visible effects upon the cells up to 40 V. Above this magnitude, due to a more homogenous distribution of the electric field, the formation and growth of the biofilm become more uniform. At around 60 V, the distance between the high electric gradient regions decreases, leading to an almost uniform distribution of the electric field and, therefore, to a shift from dielectrophoretic to electrophoretic forces acting upon the bacterial cells.

Dexamethasone is one of the most often used corticosteroid drugs for sensorineural hearing loss treatment, and is used either by intratympanic injection or through systemic delivery. In this study, a biopolymer lipid hybrid microcarrier was investigated for enhanced local drug delivery and sustained release at the round window membrane level of the middle ear for the treatment of sensorineural hearing loss (SNHL). Dexamethasone-loaded and dexamethasone-free microparticles were prepared using biopolymers (polysaccharide and protein, pectin and bovine serum albumin, respectively) combined with lipid components (phosphatidylcholine and Dimethyldioctadecylammonium bromide) in order to obtain a biopolymer–liposome hybrid system, with a complex structure combining to enhance performance in terms of physical and chemical stability. The structure of the microparticles was evaluated by FTIR, XRD, thermal analysis, optical microscopy, and scanning electron microscopy (SEM). The encapsulation efficiency determination and the in vitro Dexamethasone release study were performed using UV-Vis spectroscopy. The high value of encapsulation efficiency and the results of the release study indicated six days of sustained release, encouraging us to evaluate the in vitro cytotoxicity of Dexamethasone-loaded microparticles and their influence on the cytotoxicity induced by Cisplatin on auditory HEI-OC1 cells. The results show that the new particles are able to protect the inner ear sensory cells.

A realistic modelling of the way biofilms form and evolve in time requests a dynamic approach. In this study, the proposed route uses continuous-flow bioreactors under controlled flow rates and temperature in the culture medium containing bacteria or fungi. 3D printed, Polylactic acid (PLA), flow-based bioreactors with integrated copper electrodes were used to investigate the effect of dielectrophoresis on the formation and growth of Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, and Klebsiella pneumoniae ATCC 13883 biofilms. Bacterial suspensions of 1McF turbidity have been prepared and circulated through the bioreactors. At the same time, a 30 V potential difference was applied on the system. The effect of the non-uniform electric field induced upon the bacterial cells was determined using quantitative methods, such as an adjusted microtiter plate technique, as well as spectral domain optical coherence tomography (SD-OCT) images. The morphology and the surface quality of the biofilms were investigated using Scanning Electron Microscopy (SEM) images. The results show that the different bacterial cells present a positive dielectrophoretic behaviour, with the preferential formation of biofilms in the high field gradient region.

This paper presents a comparative study on the effects of the in-situ surface modifications performed on “H” type microfluidic systems obtained via additive manufacturing. The microsystem was printed using a polylactic acid filament on an Ender-5 Pro printer. The surface modification of the main channel was done using chloroform by two different methods: vapor smoothing and flushing. The obtained surface roughness was studied using an optical microscope and the ImageJ software, as well as scanning electron microscopy. The effect of the channel surface treatment upon the characteristics of the fluid flow was assessed. The microfluidic systems were used for the dynamic study of biofilm growth of Candida albicans (ATCC 10231). The influence of the surface roughness of the main channel on the formation and growth of the biofilm was studied using quantitative methods, scanning electron microscopy imaging as well as optical coherence tomography.

Background: Bacterial biofilm formation (BBF) proves itself to be in the spotlight of microbiology research due to the wide variety of infections that it can be associated with, the involvement in food spoilage, industrial biofouling and perhaps sewage treatment. However, BBF remains difficult to study due to the lack of standardization of the existing methods and the expensive equipment needed. We aim to describe a new inexpensive and easy to reproduce protocol for a 3D-printed microfluidic device that can be used to study BBF in a dynamic manner. Methods: We used the SolidWorks 3D CAD Software (EducationEdition 2019–2020, Dassault Systèmes, Vélizy-Villacoublay, France) to design the device and the Creality3D Ender 5 printer (Shenzhen Creality 3D Technology Co., Ltd., Shenzhen, China) for its manufacture. We cultivated strains of Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. For the biofilm evaluation we used optical coherence tomography (OCT), scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy and crystal violet staining technique. Results: Based on the analysis, Enterococcus faecalis seems to produce more biofilm in the first hours while Pseudomonas aeruginosa started to take the lead on biofilm production after 24 h. Conclusions: With an estimated cost around €0.1285 for one microfluidic device, a relatively inexpensive and easy alternative for the study of BBF was developed.

Drug delivery systems are the most researched pharmaceutical formulation, representing promising tools in the treatment of cancer.Doxorubicin is an anti-tumour drug, widely used in malignant diseases, but with serious adverse effects.The aim of this study was to develop an analytical strategy for the evaluation of the encapsulation and release of this drug from delivery systems.The electrochemical oxidation process of doxorubicin has been studied using pencil graphite electrode by a fully optimized differential pulse voltammetry procedure.This electro-analytical method was successfully applied for the evaluation of the encapsulation and release profile of doxorubicin from biocompatible and biodegradable microcapsules, UV-Vis spectroscopy being applied as control method. RezumatSistemele de transport la țintă sunt cele mai cercetate formulări farmaceutice fiind promițătoare pentru tratamentul cancerului.Doxorubicina este un antitumoral utilizat pe scară largă în afecțiunile maligne, dar care produce reacții adverse serioase.Scopul acestui studiu a fost de a dezvolta o strategie analitică pentru evaluarea încapsulării și eliberării acestui medicament din sisteme de transport la țintă.Procesul de oxidare electrochimică a doxorubicinei a fost studiat utilizând mina de creion și o procedură optimizată de voltametrie puls diferențială.Această metodă electro-analitică a fost aplicată cu succes pentru evaluarea procesului de încărcare și eliberare a doxorubicinei din microcapsule biocompatibile, spectroscopia UV-Vis fiind utilizată ca metodă de control.

This work proposes a novel complex multi-layered material consisting of porous titanium as a substrate and a complex coating consisting of a chitosan film engulfing microsphere loaded with growth factors such as BMP2 (bone morphogenic protein 2) and IGF1 (insulin-like growth factor-1). The microspheres were obtained through deposition of dual layers of calcium cross linked pectin–chitosan/pectin polyelectrolyte onto a BSA (bovine serum albumin) gel core. The multilayer was conceived to behave like a 3rd generation biomaterial, by slow delivery of viable growth factors around implants, and to assist the healing of implantation wound and the development of new vital bone. The biologic effect of the delivery of growth factors was studied in vitro, on MSC-CD1 mesenchymal stem cells, and in vivo, on CD1 mice. Proliferation and differentiation of cells were accelerated by growth factors, especially IGF1 for proliferation and BMP2 for differentiation. In vivo tests analyzed histologically and by MicroCT show a more structured tissue around BMP2 samples. The present concept will give the best clinical results if both growth factors are delivered together by a coating film that contains a double population of microcarriers.

The development of systems for targeted delivery of Sorafenib in unresectable hepatocellular carcinoma to reduce the systemic toxicity is a challenge. In our article, we successfully prepared core-shell microcapsules based on bovine serum albumin gel with polyelectrolyte complex multilayer shell of polysaccharides with opposite charges, hyaluronic acid, and chitosan, encapsulating Sorafenib, as targeting delivery system for improved hepatocellular carcinoma therapy. A bovine serum albumin gel core was formed by a method based on a sacrificial CaCO3 template, followed by the multilayer shell build-up of Ca2+ cross-linked hyaluronic acid hydrogel, and subsequently alternating multilayers of the polyelectrolyte complex formed between hyaluronic acid and chitosan. The following techniques: Fourier-transform infrared and UV-Vis spectroscopy, X-ray diffraction, differential scanning calorimetry, confocal laser scanning microscopy, atomic force microscopy, and scanning electron microscopy were used for the physicochemical characterization. These tests revealed the spherical shape of core-shell type, the micro-size, as well as the composition of microcapsules after their synthesis and proved the successful encapsulation and release of the drug. The promising results regarding encapsulation efficiency, Sorafenib release profile and cytotoxicity on HepG2 and mesenchymal stem cells, recommend Sorafenib loaded microcapsules as suitable targeted drug carriers for further in vivo studies for hepatocellular carcinoma therapy.

Abstract The aim of this study is to develop core shell microcapsules of bovine serum albumin (BSA) gel with a complex polyelectrolite multilayer shell of natural polysaccharides with opposite charges, pectin (P), chitosan (Chi), and hyaluronic acid (HA) respectively, encapsulating Doxorubicin (Dox) as a carrier for targeted anti-tumoral treatment of hepatic cell carcinoma (HCC). A sacrificial CaCO3 template method was used in order to obtain microcapsules with a BSA gel core and a layer-by-layer (Lbl) deposition technique of polyelectrolite complexes formed between P/Chi in the inner layers and HA/Chi in the outer shell layers. The preformed microcapsules, BSA gel/P/Chi/HA, noted as ms, have been applied for Dox encapsulation (ms-Dox). Dox encapsulation and release in different pH media were studied in order to elucidate the interactions between pH dependently charged species involved in the Dox loading/releasing processes. The structure characterization of ms/ms-Dox was evaluated by FTIR and UV-Vis spectroscopy, X-ray diffraction, thermal analy sis, optical microscopy, confocal laser scanning microscopy, and scanning electron microscopy. The in vitro study for citotoxicity assessment on normal and tumoral cells of both ms and ms-Dox was performed using mesenchymal stem cells (MSCs) and Hep2G HCC cell lines. Results of physical-chemical analyses confirm the successful encapsulation of Dox in ms, and the in vitro biological study recommends ms-Dox as a candidate for future in vivo research as a targeted anti-tumoral treatment modality applications. Graphical Abstract

The aim of this work was to develop a novel fully natural drug delivery system for the treatment of acne, based on core-shell microcapsules that contain Berberine (Brb). The two main objectives of the work were: a) the synthesis and the characterization of complex microcapsules (ms), ms encapsulating Berberine (ms-Brb), and b) in vitro evaluation of the release of Brb, of the cytotoxicity on normal skin cells and of the antimicrobial effect on Cutibacterium acnes (formerly Propionibacterium acnes) (C. acnes). For a), bovine serum albumin (BSA) gel-core microcapsules with alternating multilayer shells of calcium cross-linked Pectin (P) hydrogel and the polyelectrolyte complex formed by P and Chitosan (Chi) (BSA gel/P/Chi/P) were synthesized. The BSA gel-core microcapsules were obtained using a sacrificial CaCO3 template method, while the multilayer shell was formed through a technique consisting in the layer-by-layer (Lbl) deposition of polyelectrolyte complex formed by P and Chi. Brb was encapsulated into the resulting microcapsules, by a process of diffusion from solution. The structure characterization of ms/ms-Brb was performed by FTIR and UV–Vis spectroscopy, X-ray diffraction, confocal laser scanning microscopy, and scanning electron microscopy. The in vitro assessment of ms/ms-Brb cytotoxicity on skin cells was performed using keratinocyte (HaCaT) cell line. Results of physicochemical analyses confirm the successful encapsulation of Brb in ms, and the in vitro biological study recommends ms-Brb as a candidate for future in vivo research targeting anti-acne treatment.

This paper alms to develop a bloactive biomaterial based on porous titanium coated with chitosan (Chi) hydrogel film (Chi(hf)), which releases antibiotic, for tissue engineering of bone. The chosen antibiotic was Tetracycline (Tet); as a carrier, we used core-shell microcapsules of Bovine Serum Albumin (BSA) gel with k-carrageenan/chitosan polyelectrolite complex multilayer shell (xns). The structures of both Chi(hf) and Tet-loaded microcapsules (Tet-ms) were characterized by: FTIR, XRD, SEM, CISM, Fluorescence spectroscopy, and Fluorescence optical microscopy. The Tet release in pH 7.4 PBS is much slower from Tet-ms embedded in Chi(hf) than simply from Tetms. The values of mechanical properties of Chi films reveal significant adhesiveness to the "skin model" film, a good premise for implant anchorage and osseointegration. The in vitro biological study of the film that releases the antibiotic indicates a good biocompadbility and the assessment of antibacterial activity shows a prolonged release of Tet, avoiding the biofilm formation and its adhesion.

The aim of the paper is to obtain and characterize k-carrageenan-chitosan dual hydrogel multilayers shell BSA gel microcapsules, as a carrier for curcumin, and as a possible antitumoral agent in biological studies. We used the CaCO3 template to synthesize non-toxic CaCO3/BSA particles as microtemplates by coprecipitating a CaCl2 solution that contains dissolved BSA, with an equimolar Na2CO3 solution. The microcapsules shell is assembled through a layer-by-layer deposition technique of calcium cross-linked k-carrageenan hydrogel alternating with polyelectrolite complex hydrogel formed via electrostatic interactions between k-carrageenan and chitosan. After the removal of CaCO3 through Ca2+ complexation with EDTA, and by a slightly treatment with HCl diluted solution, the BSA core is turned into a BSA gel through a thermal treatment. The BSA gel microcapsules were then loaded with curcumin, through a diffusion process from curcumin ethanolic solution. All the synthesized particles and microcapsules were stucturally characterized by: Fourier Transform Infrared Spectroscopy, UV-Vis Spectrometry, X-ray diffraction, thermal analysis, fluorescence spectroscopy, fluorescence optical microscopy, confocal laser scanning microscopy and scanning electron microscopy. The behavior of curcumin loaded microcapsules in media of different pH (SGF, SIF and PBS) was studied in order to reveal the kinetics and the release profile of curcumin. The invitro evaluation of the antitumoral activity of encapsulated curcumin microcapsules on HeLa cell line and the primary culture of mesenchymal stem cells is the main reason of the microcapsules synthesis as BSA-based vehicle meant to enhance the biodisponibility of curcumin, whose anti-tumor, anti-oxidant and anti-inflammatory properties are well known.

In the present study, Zn-hydroxyapatite (Zn-HA) was synthesized, the powder was thermally treated at different temperatures and then characterized. The Zn-HA powder was characterized mainly by FTIR and XRD, but have been performed investigations like SEM, BET and size distribution. The addition of ZnO in hydroxyapatite causes alleged interactions with the existing groups in HA, which amend the corresponding signals to these groups in the IR spectra. X-ray diffractograms for samples (untreated and heat-treated) have been recorded and microstructural parameters for the all samples have been calculated. The obtained average sizes of the crystallites and the network tensions support the idea that Zn-HA powders are nanostructured. The SEM images and size distributions for Zn-HA indicate a cluster of crystals with nanometer-scale of the population-base. Was determined the adsorption-desorption isotherms for Zn-HA powder at 100 o C and 800 o C. The dates obtained from the analysis of particle size distribution indicates for the Zn-HA powder an size distribution for granules in the range from 0.05 to 0.3μm

The aim of this paper is obtaining and characterizing hydrogels based on different ratios of oxidized alginate (oA) and k-carrageenan (C), chemically cross-linked with adipic dihydrazide (adh). The alginate (A) was first oxidized with sodium metaperiodate in order to transform it into the dialdehyde derivative, a more reactive compound than alginate. A known procedure for oxidation of alginate with sodium metaperiodate in ethanol-water in order to improve alginate reactivity by transforming the hydroxyl end-groups into dialdehyde was used, preceded by a partially cleavage of the alginate chains. In the second stage, the mixture of dialdehydic derivative of oxidized alginate, k-carrageenan and glycerol subjected to reaction with adipic dihydrazide leads to a Semi-Interpenetrated Network covalently cross-linked alginate/k-carrageenan hydrogel (oAC adh ), based on the dihydrazone compound which is responsible for the chemical cross-linking. Pure alginate, k-carrageenan, oxidized alginate, adipic dihydrazide and the cross-linked hydrogel were characterized by: FTIR, XRD, and SEM.

A series of six experimental dental copolymers of different compositions has been prepared from new synthesized Bis-GMA-type oligomers and triethyleneglicol dimethacrylate by photochemical initiation of polymerization. The paper studies the influence of the chemical composition upon the extent of polymerization, mechanical properties and water sorption of the experimental copolymers. The corresponding commercial Bis-GMA-based copolymers were used as control. The extent of the polymerization, determined by FTIR method, ranged between 61.67% for the new copolymers containing 75% bis-GMA-type oligomers and 79.6% for the new copolymers containing 50% bis-GMA-type oligomers in the matrix. From the comparison of the mechanical properties, we came to the conclusion that the values for compressive strengths and diametral tensile strengths were in the same range to those obtained for the corresponding commercial Bis-GMA-based copolymers, while the flexural strength values were higher than the values for to corresponding control copolymers. The water sorption values were in the limit of clinical requirements.

The purpose of this work was to prepare an alginate/k-carrageenan composite film cross-linked with CaCl2 that could be used in biomedical applications. The influence of the alginate/carrageenan ratio on the composite films properties was studied in order to establish the optimal composition of the films. Several characterization methods such as: FTIR, XRD, TG/DTG, SEM were used, and the mechanical properties and the swelling behaviour of the obtained composite films were studied. (c) 2011 Elsevier B.V. All rights reserved.

The paper presents methodologies for the determination of corn starch packaging ultimate biodegradability under controlled composting conditions by measurement of the amount of carbon dioxide evolved and the degree of packaging disintegration at the end of the test. The composting takes place in an installation with controlled temperature, aeration and humidity.