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De Quervain’s thyroiditis, sometimes referred to as subacute thyroiditis (SAT), is the most common granulomatous disease of the thyroid, typically found after a viral infection in middle-aged women. The mRNA encoding for the angiotensin-converting enzyme-2 (ACE-2) receptor is expressed in follicular thyroid cells, making them a potential target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides infection, SARS-CoV-2 vaccines have also been implicated in SAT pathogenesis. We present a case of a woman developing SAT following vaccination with Comirnaty by Pfizer Inc. (New-York, USA). We performed a systematic review of similar cases available in the literature to provide a better understanding of the topic. We searched the databases PubMed and Embase and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patient records were then sorted according to the type of administered vaccine and a statistical analysis of the extracted data was performed. No statistically significant difference between mRNA vaccines and other vaccines in inducing SAT was found, nor was any found in terms of patient demographics, symptoms at presentation, initial, or follow-up blood tests. In our case report, we described the possible association between SARS-CoV-2 mRNA-based vaccine Comirnaty and SAT.

We describe how the organocatalytic, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-based lactide ring-opening polymerization can be effectively performed in a very polar solvent, N-methylpyrrolidone (NMP). Due to a low ceiling temperature, this “living” mechanism has been unreported to date, but we here demonstrate that through a combination of low temperature and repeated monomer additions (starve-fed process), this mechanism enables the generation of a plethora of multifunctional homo- and (stereo)block-poly(lactide)s (PLAs) with exquisite control of the molecular weight dispersity (typically Đ < 1.1) and topology (from linear through 4-, 6-, or 8-armed stars and up to ∼140 armed combs). They are scarcely obtainable or inaccessible through more classical synthetic methods due to the poor solubility of multifunctional initiators (polyols) in most organic solvents and monomer melts. In these precisely designed structures, branching significantly altered the nature of the materials’ hydrolytic degradation, allowing them to acquire a pronounced surface character (as opposed to the bulk degradation of linear polymers). Finally, we have assessed the amenability of this method to in situ block copolymerization by using the tacticity of PLLA blocks in PLLA-b-PDLLA versus PDLLA-b-PLLA (L-LA polymerized before or after DL-LA) as a sensitive method to detect (stereochemical) defects.

The impact of the coronavirus disease (COVID-19), caused by the novel coronavirus SARS-CoV-2, continues to be widespread, with more than 100 million cases diagnosed in more than 220 countries since the virus was first identified in January 2020. Although patients with mild to moderate forms of COVID-19 could be efficiently managed at home, thus reducing the pressure on the healthcare system and minimizing socio-psychological impact on patients, no trial has been proposed, conducted, or even published on COVID-19 home therapy to date. These expert opinions provide indications on the therapeutical at home management of COVID-19 patients, based on the evidence from the literature and on current guidelines.

Introduction Critically ill patients with COVID-19 are at increased risk of developing a hypercoagulable state due to haemostatic changes directly related to the SARS-CoV-2 infection or to the consequence of the cytokine storm. Anticoagulation is now recommended to reduce the thrombotic risk. Ilio-psoas haematoma (IPH) is a potentially lethal condition that can arise during the hospitalization, especially in intensive care units (ICUs) and frequently reported as a complication of anticoagulation treatment. Materials and methods We report a case series of seven subjects with SARS-CoV-2 pneumonia complicated by Ilio-psoas haematomas (IPHs) at our COVID-Hospital in Rome, Italy. Results Over the observation period, 925 subjects with confirmed SARS-CoV-2 infection were admitted to our COVID-hospital. Among them, we found seven spontaneous IPHs with an incidence of 7.6 cases per 1000 hospitalization. All the reported cases had a severe manifestation of COVID-19 pneumonia, with at least one comorbidity and 5/7 were on treatment with low weight molecular heparin for micro or macro pulmonary thrombosis. Conclusions Given the indications to prescribe anticoagulant therapy in COVID-19 and the lack of solid evidences on the optimal dose and duration, it is important to be aware of the iliopsoas haematoma as a potentially serious complication in COVID-19 inpatients.KEY MESSAGECritically ill patients with COVID-19 are at increased risk of hypercoagulability state and anticoagulation therapy is recommended.Ilio-psoas haematoma (IPH) is found to be a complication of anticoagulation regimen especially in severe COVID-19 cases.An incidence of 7.6 cases per 1000 admission of IPHs was reported.Hypoesthesia of the lower limbs, pain triggered by femoral rotation, hypovolaemia and anaemia are the most common symptoms and signs of IPHs that should alert physician.

Tissue contractures are processes of cell-mediated contraction, irreversible in nature and typically associated with fibrotic phenomena. Contractures can be reproduced in vitro; here, we have used a medium-throughput model based on fibroblast-seeded fibrin (the 'contracture well'). Firstly, we show how profoundly these processes depend on the location of the contractile cells: when on top of the material, fibroblasts produce an interfacial contracture (analog to capsular contraction around an implant), which tries and bends the construct; when seeded inside the material, they initiate a bulk contracture (analogue to a wound bed closure) that shrinks it from within. Secondly, we demonstrate that the interfacial and bulk contractures are also mechanically and biologically different processes. Thirdly, we show the potentially predictive value of this model, since it not only recapitulates the effect of pro-fibrotic factors (TGF-β1 for dermal (myo)fibroblasts), but can also indicate the fibrotic potential of a given cell population (here, dystrophic myoblasts more fibrotic than healthy or genetically corrected ones), which may have important implications in the identification of appropriate therapies.

A convalescent, non-severe, patient with COVID-19 was enrolled as a hyper-immune plasma voluntary donor by the Immuno-Hematology and Transfusion Unit of the Regina Elena National Cancer Institute in Rome, under the TSUNAMI national study criteria. During a nearly 6-month period (May–October 2020), the patient was closely monitored and underwent four hyperimmune plasma collections. Serum SARS-CoV-2 (anti-S + anti-N) IgG and IgM, anti-S1 IgA, and neutralizing titers (NTs) were measured. Anti-SARS-CoV-2 antibody levels steadily decreased. No correlation was found between anti-S/anti-N IgG and IgM levels and viral NT, measured by either a microneutralization test or the surrogate RBD/ACE2-binding inhibition test. Conversely, NTs directly correlated with anti-S1 IgA levels. Hyperimmune donor plasma, administered to five SARS-CoV-2 patients with persistent, severe COVID-19 symptoms, induced short-term clinical and pathological improvement. Reported data suggest that high NTs can persist longer than expected, thus widening hyperimmune plasma source, availability, and potential use. In vitro RBD/ACE2-binding inhibition test is confirmed as a convenient surrogate index for neutralizing activity and patients’ follow-up, suitable for clinical settings where biosafety level 3 facilities are not available. IgA levels may correlate with serum neutralizing activity and represent a further independent index for patient evaluation.

Objectives During the COVID-19 pandemic, several studies described an increased chance of developing pulmonary embolism (PE). Several scores have been used to predict the occurrence of PE. In this systematic review, we aim at summarizing the literature on predicting rules for PE in hospitalized COVID-19 patients (HCPs). Methods PUBMED and EMBASE databases were searched to identify articles (1 January 2020-28 April 2021) presenting data pertaining the use of a prediction rule to assess the risk for PE in adult HCPs. The investigated outcome was the diagnosis of PE. Studies presenting data on the use of a single laboratory assay for PE prediction were excluded. Included studies were appraised for methodological quality using the Newcastle - Ottawa Quality Assessment Scale for Cohort Studies (NOS). Results We obtained a refined pool of 12 studies, for a total of 5 scoring systems (Wells score, Geneva score, CHADS2/CHA2DS2VASc/M-CHA2DS2VASc, CHOD score, Padua Prediction Score), and 4526 patients. Only one score was specifically designed for HCPs. Three and nine included studies were prospective and retrospective cohort studies, respectively. Among the examined scores, CHOD score seems promising in terms of predictive ability. Conclusion New prediction rules, specifically developed and validated for estimating the risk of PE in HCP, differentiating ICU from non-ICU patients, and taking into account anticoagulation prophylaxis, comorbidities and the time from COVID-19 diagnosis are needed.

Background Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia.Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50-77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95%CI 3.2-26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7-15.9) in those exposed to pLMWH;p-value=0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95%CI 0.51-3.79) for patients with an admission PaO2/FiO2 < 300 mmHg and 0.27 (0.03-2.18) for those with PaO2/FiO2 >300 mmHg;p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

Chemokine-induced chemotaxis mediates physiological and pathological immune cell trafficking, as well as several processes involving cell migration. Among them, the role of CXCL12/CXCR4 signaling in cancer and metastasis is well known, and CXCR4 has been often targeted with small molecule-antagonists or short CXCL12-derived peptides to limit the pathological processes of cell migration and invasion. To reduce CXCR4-mediated chemotaxis, we adopted a different approach. We manufactured poly(lactic acid-co-glycolic acid) (PLGA)/Pluronic F127 nanoparticles through microfluidics-assisted nanoprecipitation and functionalized them with streptavidin to docking a biotinylated CXCL12 to be exposed on the nanoparticle surface. Our results show that CXCL12-decorated nanoparticles are non-toxic and do not induce inflammatory cytokine release in THP-1 monocytes cultured in fetal bovine and human serum-supplemented media. The cell internalization of our chemokine receptor-targeting particles increases in accordance with CXCR4 expression in FBS/medium. We demonstrated that CXCL12-decorated nanoparticles do not induce cell migration on their own, but their pre-incubation with THP-1 significantly decreases CXCR4+-cell migration, thereby antagonizing the chemotactic action of CXCL12. The use of biodegradable and immune-compatible chemokine-mimetic nanoparticles to reduce cell migration opens the way to novel antagonists with potential application in cancer treatments and inflammation.

Funder: AstraZeneca; doi: http://dx.doi.org/10.13039/100004325, Funder: University of Manchester; doi: http://dx.doi.org/10.13039/501100000770, This study is about fine tuning the targeting capacity of peptide-decorated nanoparticles to discriminate between cells that express different integrin make-ups. Using microfluidic-assisted nanoprecipitation, we have prepared poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles with a PEGylated surface decorated with two different arginine-glycine-aspartic acid (RGD) peptides: one is cyclic (RGDFC) and has specific affinity towards αvβ3 integrin heterodimers; the other is linear (RGDSP) and is reported to bind equally αvβ3 and α5β1. We have then evaluated the nanoparticle internalization in two cell lines with a markedly different integrin fingerprint: ovarian carcinoma A2780 (almost no αvβ3, moderate in α5β1) and glioma U87MG (very high in αvβ3, moderate/high in α5β1). As expected, particles with cyclic RGD were heavily internalized by U87MG (proportional to the peptide content and abrogated by anti-αvβ3) but not by A2780 (same as PEGylated particles). The linear peptide, on the other hand, did not differentiate between the cell lines, and the uptake increase vs. control particles was never higher than 50%, indicating a possible low and unselective affinity for various integrins. The strong preference of U87MG for cyclic (vs. linear) peptide-decorated nanoparticles was shown in 2D culture and further demonstrated in spheroids. Our results demonstrate that targeting specific integrin make-ups is possible and may open the way to more precise treatment, but more efforts need to be devoted to a better understanding of the relation between RGD structure and their integrin-binding capacity.

The Gram-positive, anaerobic bacterium Clostridioides difficile (CD) represents the most common cause of nosocomial diarrhea worldwide and is responsible for increased morbidity and mortality, and prolonged hospital stays [...]

In this study, a textile-based wearable strain sensor is fabricated to monitor human muscular activities with high sensitivity and large working range. To achieve electrical conductivity, a gum-like sticky polyvinyl acetate-co-vinyl laurate polymer (commercial name: VINNAPASS) is mixed with 50 wt % of carbon nanofiber (CNFs) using ethyl acetate as co-solvent. The VINNAPASS/CNFs-based ink is spray coated onto a stretchable polyethylene terephthalate fabric (commercial name: Lycra) and subsequently covered and stabilized with polydimethylsiloxane protective layer. Another reference sensor is also prepared using thermoplastic polyurethane (TPU) with equal concentration of CNFs. The strain sensor made with VINNAPASS demonstrated sheet resistance, maximum elongation at break, gauge factor (GF) and working range of 32.27 ± 1.60 Ω/□, 230 ± 6%, 67.12, >170% as compared to 48.44 ± 2.33 Ω/□, 122 ± 7%, 39.97 and ~100% for the sensor made with TPU, respectively. Moreover, the VINAPASS-based strain sensor displayed complete self-healing and >90% reversible electrical properties on damage, while the TPU-based sensor was not healable. Finally, the VINNAPASS-based sensor is used to monitor folding-unfolding of human finger and wrist as well as bicep muscle contraction and relaxation, and is envisioned for monitoring human muscular motions during physical activities and exercising.

We have employed microfluidics (cross-shaped chip) for the preparation of drug-loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles. The polymer precipitates from an acetone solution upon its controlled laminar mixing (flow focusing) with an aqueous solution of a surfactant, allowing for an operator-independent, up-scalable and reproducible preparative process of nanoformulations. Firstly, using PEGylated surfactants we have compared batch and microfluidic processes, and showed the superior reproducibility of the latter and its strong dependency on the acetone/water ratio (flow rate ratio). We have then focused on the issue of purification from free surfactant, and employed advanced characterization techniques such as flow-through dynamic light scattering as the in-line quality control technique, and field flow fractionation (FFF) with dynamic and static light scattering detection, which allowed the detection of surfactant micelles in mixture with nanoparticles (hardly possible with stand-alone dynamic light scattering). Finally, we have shown that the choice of polymer and surfactant affects the release behaviour of a model drug (paclitaxel), with high molecular weight PLGA (RG756) and low molecular weight surfactant (tocopheryl poly(ethylene glycol) 1000 succinate, TPGS) apparently showing higher burst and accelerated release.

Hybrids composed of liposomes (L) and metallic nanoparticles (NP) hold great potential for imaging and drug delivery purposes. However, the efficient incorporation of metallic nanoparticles into liposomes using conventional methodologies has so far proved to be challenging. In this study, we report the fabrication of hybrids of liposomes and hydrophobic gold nanoparticles of size 2-4 nm (Au) using a microfluidic assisted self-assembly process. The incorporation of increasing amounts of Au nanoparticles into liposomes was examined using microfluidics and compared to L-AuNP hybrids prepared by the reverse-phase evaporation method. Our microfluidics strategy produced L-AuNP hybrids with a homogeneous size distribution, smaller polydispersity index, and a 3-fold increase in loading efficiency when compared to those hybrids prepared using the reverse-phase method of production. Quantification of the loading efficiency was determined by ultraviolet spectroscopy, inductively coupled plasma mass spectroscopy and centrifugal field flow fractionation and confirmed qualitatively by transmission electron microscopy. The higher loading of gold nanoparticles into the liposomes achieved using microfluidics produced a slightly thicker and more rigid bilayer as determined with small angle neutron scattering. These observations were confirmed using fluorescent anisotropy and atomic force microscopy, respectively. Structural characterization of the liposomal-nanoparticle hybrids with cryo-electron microscopy revealed the co-existence of membrane-embedded and interdigitated nanoparticle-rich domains suggesting AuNP incorporation through hydrophobic interactions. The microfluidic technique that we describe in this study allows for the automated production of monodisperse liposomal-nanoparticle hybrids with high loading capacity highlighting the utility of microfluidics to improve the payload of metallic nanoparticles within liposomes, thereby enhancing their application for imaging and drug delivery.

The rapid vascularisation of biomaterials and artificial tissues is a key determinant for their in vivo viability and ultimately for their integration in a host; therefore promoting angiogenesis and maintaining the newly formed vascular beds has become a major goal of tissue engineering. The arteriovenous loop (AVL) has been an extensively studied platform which integrates microsurgery with cells scaffolds and growth factors to form neotissues. Most AVL studies to date are limited to larger animal models, which are surgically easier to perform, but have inherent limits for the understanding and interrogation of the underlying in vivo mechanisms due the paucity of transgenic models. Here, we demonstrate for the first time in a mouse model the utility of the AVL in the de novo production of vascularized tissue. We also present the combined use of the model with 3D printed chambers, which allow us to dictate size and shape of the tissues formed. This novel platform will allow for an understanding of the fundamental mechanisms involved in tissue generation de novo.

Herein, the development of biobased colorimetric pH porous indicators composed of a polyvinyl alcohol, polyvinyl pyrrolidone and microcrystalline cellulose functionalized with anthocyanins deriving from red cabbage, is presented. As revealed, the presence of 62.5%wt. of microcrystalline cellulose in the composite improves the stability of the porous system in aqueous environments, enhances the porosity, the pores’ interconnectivity and reduces the pores’ size that in turn significantly improves the responsiveness of the porous indicator to acidic or basic vapors. Specifically, the developed material shows distinct color change when subjected to acidic or basic vapors with a response 6 times faster compared to the indicator without any microcrystalline cellulose content. The color changes are reversible, making possible the use of the same indicator for several times. When the developed material was introduced in a package containing fresh prawns or chicken, its color was efficiently modified after one day of storage at ambient conditions demonstrating the possibility to be used as a food spoilage indicator. We prove by CIELab analysis that all color changes can be easily perceived visually, as the differences between the initial and the final color of the indicator after its interaction with the modified environment are well above the limit for visual perception. Therefore, the presented colorimetric porous indicator is suitable for multiple applications dealing with environmental protection and intelligent food packaging.

We report a novel, inexpensive and green method for preparing aqueous dispersions of various biofunctional transition-metal dichalcogenides (MoS2, WS2, TiS2 and MoSe2) and their related heterostructures directly via ultrasonic exfoliation mediated by the presence of phospholipids. The dispersions predominantly consist of few-layer flakes coated with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), as confirmed by Raman, photoluminescence and X-ray photoelectron spectroscopies. The phospholipid coating renders the flakes biofunctional, which coupled with the unique properties of transition-metal dichalcogenides and their heterostructures, suggests this method will have great potential in biological applications.

In this work we evaluate the effect of polymer composition and architecture of (PEGylated) polyesters on particle size and paclitaxel (PTX) loading for particles manufactured via microfluidic-assisted, continuous-flow nanoprecipitation using two microfluidic chips with different geometries and mixing principles. We have prepared poly ( d , l -lactic acid-co-caprolactone) (PLCL) from ring-opening polymerization (ROP) of LA and CL mixtures and different (macro) initiators (namely, 1-dodecanol, a MeO-PEG-OH, and a 4-armed star PEG-OH), rendering polyesters that vary in monomer composition (i.e. LA/CL ratios) and architecture (i.e. linear vs 4-armed star). Continuous-flow nanoprecipitation was assayed using two microfluidic chips: a cross-flow chip with a X-shaped mixing junction (2D laminar flow focusing) and a micromixer featuring a Y-shaped mixing junction and a split and recombine path (2D laminar flow focusing convinced with stream lamination for faster mixing). Nanoparticle formulations were produced with Z-average sizes in the range of 30–160 nm, although size selectivity could be seen for different polymer/chip combinations; for instance, smaller particles were obtained with Y-shaped micromixer (30–120 nm), specially for the PEGylated polyesters (30–50 nm), whereas the cross-flow chip systematically produced larger particles (80–160 nm). Loading of the anti-cancer drug paclitaxel (PTX) was also heavily influenced not only by the nature of the polyester, but also by the geometry of the microfluidic chip; higher drug loadings were obtained with the cross-flow reactor and the star block copolymers. Finally, decreasing the LA/CL ratio generally had a positive effect on drug loading.

This paper deals with simple, inexpensive and 'green' methods of production for graphene in colloidal dispersion. Herein, we report on such a method by preparing aqueous graphene dispersions via ultrasonic exfoliation in the presence of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The product predominantly consists of few-layer graphene flakes coated by DOPC with a lateral size of a few tens to hundreds of nm, as confirmed by Raman and X-ray photoelectron spectroscopies, thermogravimetric analysis (TGA), dynamic light scattering (DLS) and atomic force microscopy (AFM). The novelty of this method lies in its dependence on a typical soft matter property: the fluidity of the hydrophobic chains. Stiffer phospholipids such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, which possesses two palmitoyl chains) or 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC, one palmitoyl, one oleyl chain) are ineffective at dispersing graphene; however, in the presence of cholesterol these phospholipids also become effective mediators. The phospholipid coating renders the flakes compatible with biological environments.

The high-throughput generation of polymeric nanoparticles (PNPs) with tailored size and narrow size distribution is key for applications as relevant as sensing and nanomedicine. Here we show how cavitation bubbles in a microfluidic channel can induce rapid nanoprecipitation of PNPs with user-selectable control. Specifically, we used two tip-electrodes perpendicular to the flow to induce electrical breakdown of a polymer solution and a miscible non-solvent. As a result, a plasma is formed causing cavitation and rapid mixing of the fluids, yielding nanoprecipitates of polymer. We demonstrated mL/min generation of PNPs with a diameter as low as 150 nm and polydispersity below 0.15.

We report here on a method to functionalize silicone surfaces, which is based on the deposition of silicone-containing amphiphilic block copolymers from a colloidal water–ethanol dispersion. Using cross-linked silicones (Sylgard 184) as substrates, copolymers composed of two poly(glycerol monomethacrylate) (PGMMA) terminal blocks and a central poly(dimethylsiloxane) (PDMS) block can be effectively deposited when the PDMS content is ≥46 wt%. (≥65 mol%); the deposition provides smooth and stable surfaces, which significantly affected the protein adsorption behaviour of the substrate, suggesting a possible application in biomaterial coating. In air, the block copolymer surface films underwent a reorganization, which differs from the classical hydrophobic recovery of silicones and may be related to a disordered folding of lamellar structures. This led to a predominant surface coverage by thin, possibly monomolecular layers, which displayed a non-restructuring polar surface. However, as a consequence of the reorganization also larger aggregates were produced, albeit in relatively small numbers; these aggregates underwent a progressive hydrophobization (in this case a hydrophobic recovery) and probably dominated the contact angle behaviour of the material. In summary, the colloidal deposition of amphiphilic silicone-based block copolymers successfully modifies the surface properties of silicone substrates; however, attention must paid to reorganization phenomena in order to maximize the stability of the coating.

We report for the first time the combination of ATRP and ring-opening episulfide polymerization as a means to synthesize polysulfide-based low-dispersity amphiphilic block copolymers. The most significant finding is the possibility to perform ATRP under mild conditions using poly(propylene sulfide) macroinitiators, apparently without any significant copper sequestration by the polysulfides. Using glycerol monomethacrylate (GMMA) as a hydrophilic monomer, the polymers self-assembled in colloidal structures with a morphology depending on the PS/GMMA ratio, but also probably on GMMA degree of polymerization. We here also present a new AFM-based method to calculate the average number of amphiphilic macromolecules per micelle. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

This study focuses on the comparative evaluation of star (branched) and linear poly(L,D-lactic acid) (PDLLA) as degradable materials employed in controlled release. The polymers were prepared via ring-opening polymerization initiated by decanol (linear), pentaerythritol (4-armed star) and dipentaerythritol (6-armed star), and processed both in the form of films and nanoparticles. Independently on the length or number of their arms, star polymers degrade slower than linear polymers, possibly through a surface (vs. bulk) mechanism Further, the release of a model drug (atorvastatin) followed a zero-order-like kinetics for the branched polymers, and a first order kinetics for linear PDLLA. Using NHOst osteoblastic cells, both linear and star polymers were devoid of any significant toxicity and released atorvastatin in a bioavailable form; cell adhesion was considerably lower on star polymer films, and the slower release from theirnanoparticles appeared to be beneficial to avoid atorvastatin overdosing.

The natural turnover of free hyaluronic acid (HA) is predominantly based on its CD44-mediated internalisation in leukocytes. In a phagocytic cell model (RAW 264.7 murine macrophages) we here provide conclusive evidence that this receptor-mediated mechanism endocytosis is responsible also of the uptake of materials where HA is used as a coating agent, in this case chitosan/triphosphate nanoparticles on whose surface HA is electrostatically adsorbed. Alginate-coated nanoparticles were used as a control and they appeared to undergo a qualitatively similar endocytic process, which was mediated by a different scavenging receptor yet to be identified. In this general picture, an important, modulating role appears to be played by how receptors can cluster around individual nanoparticles. The CD44 slow representation (24-48h) enforces a limit in the amount of available HA internalisation receptors; therefore a higher affinity, and hence a higher degree of clustering, would yield a lower number of internalised nanoparticles. HA presentation can be varied by acting on nanoparticle structure/morphology, and our data suggest that a better presentation may be linked to both higher affinity and lower capacity/uptake rate. Paradoxically, this result would suggest that particles with a lower affinity for CD44 may allow a more efficient HA-mediated delivery of payloads. Copyright 2013 Elsevier Ltd. All rights reserved.

The study aimed to explore the influence of the network architecture on the mechanical properties and degradability of HA/PEG gels, and to highlight the relationship between Young's modulus and cell colonization with a selected architecture. Three different families of hyaluronic acid (HA)-based photopolymerized PEG diacrylate (PEGDA) hydrogels were compared, using different concentrations and molecular weights (64 and 234 kDa) of HA: semi-IPNs containing native HA in a PEG network (type I gels); co-networks obtained using thiolated HA as chain transfer agent during PEGDA polymerization (type II gels); co-networks obtained from the in situ preparation of a macromonomer derived from the Michael-type addition of thiolated HA on PEGDA (type III gels). From a comparative study of rheological properties and enzymatic degradability, type II gels were selected for a further study aiming to link their mechanical properties to cell spreading. Employing RGD-functionalized materials, Young's moduli were measured via AFM nanoindentation while the cell spreading behavior was quantitatively evaluated by monitoring morphology and metabolic activity (MTS assay) of L929 fibroblasts. By revealing a clear relation between increasing modulus and increasing cell spreading/proliferation, the study showed the possibility to fine tune the cell/material interactions with appropriate reactive processing techniques. © 2011 Elsevier Ltd.