Preparation of biofunctional textiles by surface functionalization based on the nanoencapsulation technique.

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Tailoring crystallinity for hemocompatible and durable PEEK cardiovascular implants

Polymers have the potential to replace metallic or bioprosthetic heart valve components due to superior durability and inertness while allowing for native tissue-like flexibility. Despite these appealing properties, certain polymers such as polyetheretherketone (PEEK) have issues with hemocompatibility, which have previously been addressed through assorted complex processes. In this paper, we explore the enhancement of PEEK hemocompatibility with polymer crystallinity. Amorphous, semi-crystalline and crystalline PEEK are investigated in addition to a highly crystalline carbon fiber (CF)/PEEK composite material (CFPEEK). The functional group density of the PEEK samples is determined, showing that higher crystallinity results in increased amount of surface carbonyl functional groups. The increase of crystallinity (and negatively charged groups) appears to cause significant reductions in platelet adhesion (33 vs. 1.5 % surface coverage), hemolysis (1.55 vs. 0.75 %∙cm$^{-2}$), and thrombin generation rate (4840 vs. 1585 mU/mL/min/cm$^{2}$). In combination with the hemocompatibility study, mechanical characterization demonstrates that tailoring crystallinity is a simple and effective method to control both hemocompatibility and mechanical performance of PEEK. Furthermore, the results display that CFPEEK composite performed very well in all categories due to its enhanced crystallinity and complete carbon encapsulation, allowing the unique properties of CFPEEK to empower new concepts in cardiovascular device design

Assessment of antioxidant and drug releasing properties of cellulose fabrics functionalized with polymeric nanoparticles as potential biofunctional garments

Drug administration through skin raised a great interest as a not invasive and sustained method to deliver active substances both at topical and systemic levels. Biofunctional textiles are a new class of materials that combine conventional fabrics with advanced drug delivery systems in order to develop a wearable functional biomaterial [1]. The present research aims to functionalize cellulosic fabrics (e.g. cotton and viscose) with curcumin (CUR)-loaded polycaprolactone (PCL) nanoparticles (NPs) in order to assess their potential as biofunctional garments. The NPs were produced by the flash nanoprecipitation technique in a confined impinging jet mixer. Such technology was proven to be a simple and scalable approach to produce polymeric nanoparticles; moreover it was successfully applied to curcumin encapsulation [2]. Nanoparticles were then characterized in terms of size and zeta potential by dynamic light scattering (DLS), while the loading capacity (LC%) and encapsulation efficiency (EE%) were measured by exploiting fluorescence spectroscopy. Cotton and viscose fabrics were functionalized by imbibition with the NPs suspensions and the effectiveness of the treatment was observed under wide-field fluorescence microscopy. The release properties of the nanoparticles suspensions were studied in vitro in a multicompartment rotating cell, while the curcumin release from textile support was tested ex vivo in a Franz diffusion cell using porcine skin as membrane. Furthermore, the antioxidant activity of the NPs and of the functionalized fabrics was measured by electron paramagnetic resonance spectroscopy. Curcumin loaded NPs were successfully prepared with good control of particle size and loading capacity, high stability over several days and encapsulation efficiency higher than 99%. Nanoparticles were successfully attached to the textiles material as evidenced by fluorescent imaging. The prepared materials showed an improved antioxidant activity and the capability of controlling curcumin release both in vivo and ex vivo. The present research shows the possibility of producing biofunctional materials by simple and scalable process and opens a route for a new generation of garments that can benefit people health

Préparation de textiles biofonctionnels par fonctionnalisation de surface basée sur la nanoencapsulation

La présente thèse a été réalisée dans le cadre du projet de doctorat joint SMD-Tex, en partenariat entre le POLITO (Italie), l’ENSAIT (France) et à l'Université de Soochow (Chine). Le but de ce travail est de proposer de nouvelles approches pour la production de textiles biofonctionnels. Ces produits sont constitués de textiles qui ont subi des traitements de finition spéciaux pour conférer des propriétés qui présentent des effets bénéfiques pour la santé de l'utilisateur.Longtemps la recherche pharmaceutique a étudié des outils nouveaux et plus efficaces pour administrer un médicament au patient. Le but de ces études est d’admiistrer des dosages thérapeutiques efficaces sur une longue période, en minimisant le nombre d'administrations requises et les effets secondaires possibles. Dans ce contexte, la peau a été considérée comme une voie de libération de médicaments locaux et systémiques. Une telle approche est plus simple et moins invasive que d'autres voies. Donc, plusieurs stratégies ont été développées pour délivrer efficacement des médicaments à travers la barrière cutanée. Parmi celles-ci, la technologie d'encapsulation permet l'incorporation des substances actives à l'intérieur des nanoparticules (NP) pour i) protéger le médicament, ii) le délivrer efficacement à travers la peau iii) contrôler la libération au fil du temps.Dans le présent travail, des NP chargés de médicament ont été produits en utilisant de la polycaprolactone (PCL) comme membrane. Les nanoparticules produites ont ensuite été utilisées pour le finissage des tissus en coton produisant des textiles biofonctionnels destinés à être utilisés comme dispositifs portables de distribution de médicaments. La technique de nanoprécipitation flash (FNP) a été exploitée pour la production des NPs en raison de sa productivitè, et simplicité. La pertinence du procédé FNP pour produire des NP destinés à être utilisés dans la préparation de textiles biofonctionnels a été étudiée. Les nanoparticules PCL ont été produites en chargeant trois médicaments différents dans le système, à savoir la caféine, la mélatonine et la curcumine. Ces médicaments sont en effet considérés comme des médicaments modèles en termes de niveau d'hydrophilie. Ce dernier est une propriété clé dans la détermination du résultat du processus d'encapsulation et de la perméation cutanée.Le procédé FNP a été exécuté en dissolvant le polymère dans un solvant organique et en faisant entrer le courant de solution en collision avec un courant d'antisolvant dans un micromélangeur, entraînant la précipitation du polymère sous forme de nanoparticules. Pour chaque substance active, les protocoles expérimentaux et les méthodes analytiques ont été ajustés pour mieux étudier le système de NP chargé de médicament. L'effet de la formulation ainsi que les paramètres du procédé sur les taille et la capacité d’enrobement des nanoparticules ont été étudiés. De plus, les formulations de NP ont été caractérisées pour obtenir des informations sur leurs propriétés physiques et chimiques par diverses techniques. Les particules ont été appliquées au textile de coton soit par des méthodes d'imbibition ou d'imprégnation. L'efficacité du traitement de fonctionnalisation a été évaluée en combinant différentes analyses. Les propriétés biofonctionnelles ont été étudiées en termes d'activité antioxydante, de facteurs de protection UV et de libération de médicaments. Pour ce dernier test, la méthode des cellules de Franz a été employée. L'étude a montré que le FNP permet de produire des NPs de PCL chargées de médicament pour les trois substances étudiées. Le traitement de finition proposé a permis de fonctionnaliser efficacement la surface du tissu. Les textiles traités ont permis de délivrer efficacement les principes actifs à la peau avec des profils de perméation dépendant des propriétés du médicament. La finition des nanoparticules confère également au coton des propriétés antioxydantes et de protection contre les UV.This study was performed in the frame of the SMD-Tex Joint Doctorate project. The doctoral research activities were carried out in three mobility periods at POLITO (Italy), Ensait (France), and University of Soochow (China). This work aims to propose novel approaches for the production of biofunctional textiles. These products consist of textile fabrics which underwent special finishing treatments to confer properties that display beneficial effects to the user's health.In the last decades, pharmaceutical research has been investigating novel and more effective tools to administer a drug to the patient. The scope of these studies is to provide effective therapeutic dosages over a long time, minimizing the number of required administrations and the possible side effects. In this context, the skin has been regarded as a potential route for the release of local and systemic drugs. Such an approach is simpler and less invasive compared to other routes. Therefore, several strategies have been developed to effectively deliver drugs across the skin barrier. Among them encapsulation technology allows the incorporation of the active substances inside nanoparticles (NPs) to i) protect the drug, ii) effectively deliver it through the skin iii) control the release over time.In the present work, drug-loaded NPs were produced by employing polycaprolactone (PCL) as shell material. The produced nanoparticles were then used to finish cotton fabrics producing biofunctional textiles to be employed as wearable drug delivery devices. The flash nanoprecipitation technique (FNP) was exploited for the nanocarrier production being identified as a simple, sustainable and efficient production process. The suitability of the FNP process to produce NPs to be used in the preparation of biofunctional textiles was investigated. The PCL nanoparticles were produced by loading three different drugs in the system i.e. caffeine, melatonin, and curcumin. Such drugs are indeed considered model drugs in terms of hydrophilicity level. The latter is a key property in determining the outcome of the encapsulation process and the dermal permeation.The FNP process was run by dissolving the polymer in an organic solvent and making the solution stream collide against an antisolvent stream in a micromixer, resulting in the polymer precipitation in the form of nanoparticles. The drugs were precipitated together with the polymer upon being added either to the solvent or the antisolvent stream. For each active substance, the experimental protocols and analytical methods were adjusted to better investigated the drug-loaded NPs system. The effect of the formulation as well as the process parameters on the properties of the nanoparticles was investigated. The process was optimized to produce particles with a diameter lower than the one of skin pores. The amount of drug loaded in particles was investigated by loading capacity (LC) and encapsulation efficiency (EE). Furtherly, the NP formulations were characterized to obtain insights on their physical, chemical, and morphological properties by various analytical techniques.The particles were applied to the cotton fabric either by imbibition or impregnation methods. The effectiveness of the functionalization treatment was evaluated combining different analyses. The biofunctional properties were studied in terms of antioxidant activity, UV protection factors, and drug release. For the latter test, the Franz cell method was employed using either artificial and excised porcine skin membranes.The study showed that the FNP allows producing drug loaded PCL NPs for all the three investigated substances. The proposed finishing treatment allowed to effectively functionalize the fabric surface. The treated textiles allowed to effectively deliver the active principles to the skin with permeation profiles dependent on the drug properties. The nanoparticle finishing also imparted cotton antioxidant and UV protection properties

Overcoming the Limits of Flash Nanoprecipitation: Effective Loading of Hydrophilic Drug into Polymeric Nanoparticles with Controlled Structure

Flash nanoprecipitation (FNP) is a widely used technique to prepare particulate carriers based on various polymers, and it was proven to be a promising technology for the industrial production of drug loaded nanoparticles. However, up to now, only its application to hydrophobic compounds has been deeply studied and the encapsulation of some strongly hydrophilic compounds, such as caffeine, remains a challenge. Caffeine loaded poly-ε-caprolactone (PCL) nanoparticles were produced in a confined impinging jet mixer using acetone as the solvent and water as the antisolvent. Caffeine was dissolved either in acetone or in water to assess the effects of two different process conditions. Nanoparticles properties were assessed in terms of loading capacity (LC%), encapsulation efficiency (EE%), and in vitro release kinetics. Samples were further characterized by dynamic light scattering, scanning electron microscopy, X-ray photo electron spectroscopy, and infrared spectroscopy to determine the size, morphology, and structure of nanoparticles. FNP was proved an effective technique for entrapping caffeine in PCL and to control its release behavior. The solvent used to solubilize caffeine influences the final structure of the obtained particles. It was observed that the active principle was preferentially adsorbed at the surface when using acetone, while with water, it was embedded in the matrix structure. The present research highlights the possibility of extending the range of applications of FNP to hydrophilic molecules

Preparation of hierarchical material by chemical grafting of carbon nanotubes onto carbon fibers

A hierarchical material was produced by grafting multiwalled carbon nanotubes (MWCTNs) onto the surface of carbon fibers. A single oxidation treatment based on the combination of strong acids and ultrasounds was employed for both materials, while grafting was obtained by mean of a mild thermal treatment. The effectiveness of the oxidation treatment was evaluated by Thermogravimetric Analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR), while the success of the grafting was studied by TGA and Field Emission Scanning Electron Microscope (FESEM) observation. Different carbon fibers (CFs)/carbon nanotubes (CNTs) weight ratios have been used in the grafting process in order to assess how the amount of grafted CNTs can affect the final morphology of the hierarchical material. A novel hierarchical structure was observed and a mechanism for its production was proposed

Production of PCL nanoparticles by flash nanoprecipitation for controlled release of caffeine

Caffeine (CAF) is one of the most consumed drug worldwide due to its large application in food, pharmaceuticals, cosmetics and supplements; upon oral administration caffeine is cleared into the stomach in 20 minutes and absorbed into the blood within 1 hour. Polycaprolactone (PCL) is biodegradable polymer extensively studied in drug delivery applications where long lasting releases are required. Caffeine was encapsulated in PCL nanoparticles by exploiting the Flash nanoprecitation technique which is well known method to encapsulate hydrophobic drug, but not yet studied on hydrophilic active principles. The nanoparticles were produced in a confined impinging jet mixer by dissolving caffeine alternatively in the solvent (acetone) or in the antisolvent (water). The effect of the process parameters on the mean particle diameter and zeta potential of the nanoparticles was investigated by Dynamic Light Scattering. A novel procedure to accurately quantify drug Loading Capacity (LC) and Encapsulation Efficiency was developed and implemented. The in vitro release kinetic was assessed by dynamic dialysis method. Nanoparticles with average diameter ranging from 250 to 500 nm were successfully produced, the mean size was correlated to the flow rate. LC and EE were assessed in the range of 10-45% and 5-25% respectively. The release test showed a delay in the peak of caffeine in blood mimicking solution up to 6 hours

Overcoming the Limits of Flash Nanoprecipitation: Effective Loading of Hydrophilic Drug into Polymeric Nanoparticles with Controlled Structure

Flash nanoprecipitation (FNP) is a widely used technique to prepare particulate carriers based on various polymers, and it was proven to be a promising technology for the industrial production of drug loaded nanoparticles. However, up to now, only its application to hydrophobic compounds has been deeply studied and the encapsulation of some strongly hydrophilic compounds, such as caffeine, remains a challenge. Caffeine loaded poly-ε-caprolactone (PCL) nanoparticles were produced in a confined impinging jet mixer using acetone as the solvent and water as the antisolvent. Caffeine was dissolved either in acetone or in water to assess the effects of two different process conditions. Nanoparticles properties were assessed in terms of loading capacity (LC%), encapsulation efficiency (EE%), and in vitro release kinetics. Samples were further characterized by dynamic light scattering, scanning electron microscopy, X-ray photo electron spectroscopy, and infrared spectroscopy to determine the size, morphology, and structure of nanoparticles. FNP was proved an effective technique for entrapping caffeine in PCL and to control its release behavior. The solvent used to solubilize caffeine influences the final structure of the obtained particles. It was observed that the active principle was preferentially adsorbed at the surface when using acetone, while with water, it was embedded in the matrix structure. The present research highlights the possibility of extending the range of applications of FNP to hydrophilic molecules

Multiscale composites based on carbon fibers and carbon nanotubes

The observation of hierarchical structures in nature has shown how great mechanical performances can be achieved by relatively weak constituents if the matter is distributed along multiple length scales[1]. In order to reproduce a biomimetic multiscale material in laboratory[2] pure carbon material have been chosen both for of the intrinsic strength of such materials and for the availability of carbon materials with different length scales (micro and nano). The chemical grafting was performed by dispersing the oxidized nanotubes (CNTs) in acetone by mean of an ultrasound probe, and by pouring the obtained dispersion over the carbon fibers (CFs) drop-by-drop, allowing the solvent evaporation. Then the CF-CNT system was heated in order to create the chemical bonding, finally the thermally treated fibers were washed with water and dried. The composite preparation was done by tape casting technology using a polyvinyl butyral matrix and modifying the type and content of the fillers: at first, only CFs or CNTs in different concentrations in order to asset the properties of the single filler; secondly, a physical mixture of CFs and CNTs; finally, the mixture of CFs and CNTs with hierarchical structure. The composite tapes were cut into specimens that underwent tensile testing. Further characterizations were done by optical microscopy and SEM observation of the fracture surfaces. The work allowed the assessment of mechanical properties and the collection of a wide and statistically sound range of data that is possible to consider reliable for modelling purposes, both because of the rigorous methodology followed in preparation and testing and because of the matching between the collected data and the ones expected by theory

Designing Polymeric Cardiovascular Biomaterials for Hemocompatibility and Mechanical Performance

One of the greatest challenges facing polymeric cardiovascular devices is the issue of hemocompatibility. Devices such as polymeric heart valves potentially offer improved mechanical properties and quality of life compared to their animal tissue counterparts. However, they are still strongly limited by problematic interactions with blood. The reduction of platelet adhesion, thrombogenicity, and calcification have been addressed in a variety of surface and bulk modification methods, generally by increasing the hydrophilic character of polymers. However, most hydrophilization processes – oxygen plasma in particular – tend to offer limited longevity. The crystallinity of polymers has previously been observed to influence the extent of platelet adhesion, though the underlying mechanisms for this phenomenon are not clear. In this research, we report on the effect of crystallinity on hemolysis, thrombogenicity, and platelet adhesion in PEEK surfaces. By tailoring the bulk crystallinity, we demonstrate changes in the surface chemical composition and propose a potential strategy to achieve longer term surface modification for improved hemocompatibility. Additionally, we explore the influence of crystallinity on the mechanical properties of thin PEEK films, establishing the multi-dimensional impact of polymer crystallinity. The results shown here may have implications for the design of polymeric cardiovascular devices and considerations that should be taken during material selection