Papers by Eleonora Marsich
Highly monodisperse colloidal coacervates based on a bioactive lactose-modified chitosan: From synthesis to characterization
Carbohydrate Polymers, Oct 1, 2017
The present contribution aims at describing the fabrication of coacervates in the nano-size range... more The present contribution aims at describing the fabrication of coacervates in the nano-size range starting from a 1-deoxylactit-1-yl chitosan (in this manuscript termed as CTL60) and the multivalent anion tripolyphosphate (TPP). Colloidal coacervates have been obtained for precise values of the molar ratio of TPP to CTL60 repeating unit. Coacervation is ensured only at pH 4.5 and not at 7.4, thus demonstrating the key role of electrostatic interactions in the stabilization of the coacervates. At a variance with chitosan, CTL60 favors the formation of highly homogeneous coacervates with very low values of the polydispersity index (PDI). Moreover, CTL60 coacervates can be freeze-dried without any cryoprotectant, they can host a model molecule and are stable up to three weeks at 4°C. Conversely, such coacervates dissolve upon increasing pH and ionic strength. By considering the bioactive polycation CTL60, the present system can be suggested as a first step in the development of innovative biologically-active nano-carriers to be used as drug delivery systems.
Immediate stress dissipation in dual cross-link hydrogels controls osteogenic commitment of mesenchymal stem cells
Carbohydrate Polymers, Feb 1, 2023
Nottingham Trent University's Institutional Repository (Nottingham Trent Repository), 2017
Colloids and interfaces, Mar 2, 2020
Herein, we synthetized and characterized polysaccharide-based complex coacervates starting from t... more Herein, we synthetized and characterized polysaccharide-based complex coacervates starting from two water-soluble biopolymers, i.e., hydrochloride chitosans and sodium hyaluronan. We used chitosans encompassing a range of molecular weights from 30,000 to 400,000 and showing different fraction of acetylated units (i.e., F A = 0.16, 0.46, and 0.63). This set of chitosans was mixed with a low molecular weight hyaluronan to promote electrostatic interactions. Resulting colloids were analyzed in terms of size, polydispersity and surface charge by Dynamic Light Scattering. The weight ratio between the two polyelectrolytes was studied as additional parameter influencing the liquid-liquid phase separation. Main results include the following: the polymers weight ratio was fundamental in dictating the colloids surface charge, whereas chitosan physical-chemical features influenced the dimension and homogeneity of colloids. This contribution presents additional understanding of the complex coacervation between these two oppositely charged polysaccharides, with the potential translation of present system in food and biomedical sectors.
Macromolecular Bioscience, Sep 4, 2017
Tissue damage caused by excessive amounts of neutrophil-derived reactive oxygen species (ROS) occ... more Tissue damage caused by excessive amounts of neutrophil-derived reactive oxygen species (ROS) occurs in many inflammatory diseases. Butyrate is a short-chain fatty acid (SCFA) with known antiinflammatory properties, able to modulate several neutrophil functions. Evidence is provided here that butyrate inhibits neutrophil ROS release in a dose-and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization and mucoadhesiveness. B-NPs appear as promising tools to limit ROS-dependent tissue injury during inflammation. Particularly, by virtue of their mucoadhesiveness, B-NPs administered by enema can be effective in the treatment of inflammatory bowel diseases.
Idrogeli Omogenei Da Derivati Oligosaccaridici Del Chitosano e Loro Applicazioni
L\u2019invenzione concerne un procedimento per la preparazione di idrogeli di derivati oligosacca... more L\u2019invenzione concerne un procedimento per la preparazione di idrogeli di derivati oligosaccaridici del chitosano e di acido borico, che permette di formare idrogeli omogenei evitando la formazione di precipitati. Sotto un altro aspetto viene descritto un idrogelo ottenibile da tale procedimento. Vengono altres\uec descritti gli usi degli idrogeli in campo biomedico e farmaceutico, nelle applicazioni di viscosupplementazione, come sostituto della matrice extracellulare e come dispositivo di somministrazione di farmaci
Sulfated lactose-modified chitosan. A novel synthetic glycosaminoglycan-like polysaccharide inducing chondrocyte aggregation
Carbohydrate Polymers, Jul 1, 2022
Lactose-modified chitosan (CTL) is sulfated using SO3·py or SO3·DMF as sulfating agents. The two ... more Lactose-modified chitosan (CTL) is sulfated using SO3·py or SO3·DMF as sulfating agents. The two products are characterized by elemental analysis, FT-IR, 1H,13C-DEPT-HSQC and 1H,13C-HSQC-TOCSY experiments which allow the extent and selectivity of chemical sulfation to be determined. Dynamic Light Scattering shows a pH-dependent association of the sulfated polysaccharides which are described as flexible by the Smidsrød's B parameter and the intrinsic viscosity at infinite ionic strength. Shear viscosity and intrinsic viscosity show that sulfation protocols lead to chain scission which is more pronounced when SO3·DMF is used. The sulfated samples are able to induce aggregation of human bone marrow mesenchymal stem cells, resulting in the formation of smaller nodules compared to the unmodified CTL sample. Over time, the sample with the higher degree of sulfation allows further aggregation between cell clusters while the sample with the lower degree of sulfation shows dissolution of the aggregates.
Macromolecular Bioscience, Sep 25, 2020
temporal complexity of living tissues. Native tissues are in fact seldom static networks; they di... more temporal complexity of living tissues. Native tissues are in fact seldom static networks; they display dynamics relevant for complex tissue homeostasis. Groundbreaking biomaterials should therefore mimic extracellular matrix (ECM) environment, dynamically respond to cell stimuli and self-remodel polymer mesh following to forces applied by cells, ECM production and neo-tissue formation. Among dynamic (out-of-equilibrium) matrices, boronic acid containing gels have shown great potential in tissue engineering and, more broadly speaking, in medicine. The binding of boronic acids to polyols leads to the formation of transient esters, especially with 1,2-and 1,3-diols. Specifically, the cross-linker behaves as a sticker, with borate residues associating and dissociating in a highly dynamic fashion. Hence, this dynamic material can flow under its own weight. Though endowed with unique features such as selfhealing, continuous network rearrangement due to cross-linker binding/unbinding dynamics may affect its final performance. Conversely, gels containing permanent cross-links bear their own weight-without apparent flow-but suffer from marked brittleness, as to hamper ultimate application thereof, especially for load-bearing conditions. Over the last few years, gels composed of dual cross-links, i.e., "temporary and weak" on one side and "permanent and strong" on the other have attracted great interest. They in fact overcome flaws above reported forming a stretchable and elastic network with respect to the counterparts containing sole permanent or temporary junctions. Poly(vinyl alcohol), polyampholytes and alginate/polyacrylamide mixtures represent the typical polymers used hitherto for assembling dual systems. However, none of them possesses inborn tissue-inductive properties. Hence, regenerative medicine longs for innovative networks showing peculiar mechanics that simultaneously could assist and direct cells in repairing injured tissues. In this contribution we describe for the first time dual cross-link hydrogels based on a lactose-derivative of chitosan, shortly named CTL, containing both temporary and permanent reticulations. CTL is a branched diol-rich polysaccharide endowed with bioactive features in terms of cartilage, bone and nerve regeneration. Recently, CTL showed the ability to form dynamic gels in the presence of boric acid as temporary Mounting evidences have recognized that dual cross-link and double-network gels can promisingly recapitulate the complex living tissue architecture and overcome mechanical limitations of conventional scaffolds used hitherto in regenerative medicine. Here, dual cross-link gels formed of a bioactive lactose-modified chitosan reticulated via both temporary (boric acid-based) and permanent (genipin-based) cross-linkers are reported. While boric acid rapidly binds to lactitol flanking diols increasing the overall viscosity, a slow temperature-driven genipin binding process takes place allowing for network strengthening. Combination of frequency and stress sweep experiments in the linear stress-strain region shows that ultimate gel strength, toughness, and viscoelasticity depend on polymer-to-genipin molar ratio. Notably, herewith it is demonstrated that linear stretching correlates with strain energy dissipation through boric acid binding/unbinding dynamics. Strainhardening effect in the nonlinear regime, along with good biocompatibility in vitro, points at an interesting role of present system as biological extracellular matrix substitute.
Hyaluronic acid/lactose-modified chitosan electrospun wound dressings – Crosslinking and stability criticalities
Carbohydrate Polymers, Jul 1, 2022
Polysaccharide electrospun wound dressings should be an effective strategy in the field of wound ... more Polysaccharide electrospun wound dressings should be an effective strategy in the field of wound care, as they combine an extracellular matrix-like structure with excellent biomimicry. However, their high hydrophilicity and large surface area cause a rapid dissolution in aqueous environments, compromising their clinical employment. In the present paper, electrospun membranes prepared using hyaluronic acid, a bioactive lactose-modified chitosan (CTL), and polyethylene oxide have been crosslinked using glutaraldehyde, genipin, EDC/NHS or thermal treatments, obtaining very poor results in terms of membrane stability. Therefore, carbonyldiimidazole (CDI) and methacrylic anhydride were investigated in an innovative way, where CDI proved to be the best compromise between nanofiber water resistance, architecture maintenance and degradability. Indeed, the swelling and degradation behavior as well as the water vapor permeability of these matrices were tested, revealing the effectiveness of the electrospun products in absorbing large amount of liquid while maintaining the balance between water retention and gas permeability.
ACS Biomaterials Science & Engineering, Sep 4, 2019
Polymeric wound dressings, an insight into polysaccharide-based electrospun membranes
Applied Materials Today, Sep 1, 2021
Abstract Chronic wounds deeply invalidate patient's quality of life, involving very high cost... more Abstract Chronic wounds deeply invalidate patient's quality of life, involving very high costs for the medical system. Numerous wound dressings have been studied over the years, and active wound dressings replaced traditional passive dressings to promote tissue regeneration and wound closure. Aiming at an optimal reproduction of the physiological environment, electrospun wound dressings are emerging since they mimic the architecture of the extracellular matrix and provide a large contact surface area, enabling exudate absorption and permeability as well as good conformability to the wound site. The use of polysaccharides offers an excellent biomimicry, as they ensure good biocompatibility, biodegradability, and non-immunogenicity. Furthermore, they possess bioactive properties, such as antimicrobial, anti-inflammatory, and antioxidant properties, which can promote and enhance the healing process. The aim of this review is to present the morphological, physical, and chemical features of an ideal wound dressing together with the traditional and the current strategies, and the already commercialized wound dressings. Moreover, the review is focused on the preparation of polysaccharide-based electrospun nanofibrous devices and on the strategies for the modulation and improvement of membrane stability and bioactivity. Lastly, a comprehensive consideration on the process and requirements that lead to the commercialization of the wound dressings is reported.
Correction to “Lactose-Modified Chitosan Gold(III)-PEGylated Complex-Bioconjugates: From Synthesis to Interaction with Targeted Galectin-1 Protein”
Bioconjugate Chemistry, Jun 22, 2022
Development of di-methacrylate quaternary ammonium monomers with antibacterial activity
Acta Biomaterialia, Jul 1, 2021
Nine antibacterial di-methacrylate monomers based on bis-quaternary ammonium salts (bis-QAMs) wer... more Nine antibacterial di-methacrylate monomers based on bis-quaternary ammonium salts (bis-QAMs) were synthesized and structurally characterized. The biological activity of the bis-QAMs was tested in terms of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on different bacterial strains achieving promising results and, in most cases, a complete bactericidal effect using a bis-QAM concentration lower than 1 mg/mL. Two of the structures showed comparable and superior activity against S. mutans than the commercial monomer 12-methacryloyloxydodecyl pyridinium bromide (MDBP). All the bis-QAMs here described were able to inhibit S. mutans biofilm formation at a concentration equal to the MIC value. From the analysis of the obtained data, some correlation regarding the structure and the antibacterial activity of the bis-QAMs could be drawn: a flexible alkyl C12 spacer between the two quaternary ammonium moieties increased the monomer antibacterial effect in comparison to the aromatic ones; the equilibrium between hydrophobic and hydrophilic moieties was directly correlated to the bactericidal range of action; the increase of the steric hindrance of the ammonium side groups might be both advantageous or disadvantageous to the antibacterial efficacy depending on the whole monomer chemical structure. Even though the possible correlation between the monomer structures and their bacteriostatic or bactericidal effect is under investigation, the monomers exhibited low cytotoxicity on human dental pulp stem cells, confirming their promising potential in the dental materials' field.
Advanced Functional Materials, Apr 23, 2022
Natural tissues and extracellular matrices (ECMs) are not purely elastic materials but exhibit di... more Natural tissues and extracellular matrices (ECMs) are not purely elastic materials but exhibit dissipative properties. Although it has recently emerged as a novel regulator of cellular responses, the contribution of material dissipation to guiding cell-fate decisions is still in its infancy. Here, a strategy for tuning the dissipation rate of viscoplastic substrates while precisely regulating linear elasticity is reported. Semi-interpenetrating substrates consisting of a rigid hydrogel network intertwined with a branched biopolymer are described. The release of these weak physical entanglements under loading dissipates the applied stress and leads to the extension of the linear elasticity. These results reveal a crucial link between this material property and cell response in 2D cultures, impacting cell migration mode and speed, vinculin-dependent focal adhesion geometry and size, F-actin organization, the transmission of forces, and Yes-associated protein nuclear translocation. It is shown that cells require joint actomyosin contractility and microtubule tension to probe the substrate and decide whether or not to adhere, revealing a clear correlation between force transmission, substrate dissipation rate, and amount of anchoring points. Overall, these findings introduce linear elasticity as a novel design parameter for assembling tunable dissipative materials to study cell mechanosensing in 2D and possibly also in 3D cultures.
Nanomaterials, Jun 27, 2019
Dental pulp stem cells (DPSCs) represent a population of stem cells which could be useful in oral... more Dental pulp stem cells (DPSCs) represent a population of stem cells which could be useful in oral and maxillofacial reconstruction. They are part of the periendothelial niche, where their crosstalk with endothelial cells is crucial in the cellular response to biomaterials used for dental restorations. DPSCs and the endothelial cell line EA.hy926 were co-cultured in the presence of Chitlac-coated thermosets in culture conditions inducing, in turn, osteogenic or angiogenic differentiation. Cell proliferation was evaluated by 3–[4,5–dimethyl–thiazol–2–yl–]–2,5–diphenyl tetrazolium bromide (MTT) assay. DPSC differentiation was assessed by measuring Alkaline Phosphtase (ALP) activity and Alizarin Red S staining, while the formation of new vessels was monitored by optical microscopy. The IL-6 and PGE2 production was evaluated as well. When cultured together, the proliferation is increased, as is the DPSC osteogenic differentiation and EA.hy926 vessel formation. The presence of thermosets ...
Bioconjugate Chemistry, Sep 14, 2018
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
POLYMERMISCHUNGEN VON ANIONISCHEN UND KATIONISCHEN POLYSACCHARIDEN UND VERWENDUNG DAVON. German Patent DE602007008879
Described in the present application are compositions comprising mixtures of polyanionic polysacc... more Described in the present application are compositions comprising mixtures of polyanionic polysaccharides and polycationic polysaccharides consisting of oligosaccharide derivatives of chitosan. In the compositions of the invention said mixtures have proven to be soluble in aqueous environments, despite ionic complexes forming between the acid polysaccharides and chitosan derivatives. Said compositions have also demonstrated significant rheological behavior with an unexpected increase in viscosity and viscoelasticity, although the polysaccharides used have relatively low average molecular weights. The said solubility and rheological behavior renders the compositions of the invention particularly advantageous from the biomedical application viewpoint, in particular for viscosupplementation and particularly in the field of articular pathologies and of ophthalmic surgery. polyme
POLYMER MIXTURES OF ANIONIC AND CATIONIC POLYSACCHARIDES AND USE THEREOF. European Patent EP2021408
Described in the present application are compositions comprising mixtures of polyanionic polysacc... more Described in the present application are compositions comprising mixtures of polyanionic polysaccharides and polycationic polysaccharides consisting of oligosaccharide derivatives of chitosan. In the compositions of the invention said mixtures have proven to be soluble in aqueous environments, despite ionic complexes forming between the acid polysaccharides and chitosan derivatives. Said compositions have also demonstrated significant rheological behaviour with an unexpected increase in viscosity and viscoelasticity, although the polysaccharides used have relatively low average molecular weights. The said solubility and rheological behaviour renders the compositions of the invention particularly advantageous from the biomedical application viewpoint, in particular for viscosupplementation and particularly in the field of articular pathologies and of ophthalmic surgery
HYDROGELE VON POLYSACCHARIDMISCHUNGEN FÜR DAS GEWEBE-ENGINEERING UND ALS WIRKSTOFFTRÄGER. German Patent DE602007004212
Cytotoxicity of experimental chitosan methacrylate polymer for dental adhesive purposes
Dental Materials, 2014
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Papers by Eleonora Marsich