Recent Advances in Nanocellulose for Biomedical Applications

ArticleinJournal of Applied Polymer Science 132:41719 · April 2015with 1,691 Reads
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Abstract
Nanocellulose materials underwent rapid development in recent years as promising biomedical materials due to their excellent physical and biological properties specially biocompatibility, biodegradability and low cytotoxicity. Recently, a significant amount of research has been directed towards fabricating advanced cellulose nanofibers with different morphologies and functional properties. These nanocellulose fibers are widely applied in medical implants, tissue engineering, drug delivery, wound healing, cardiovascular, and other medical applications. This review provides a reflection of the recent advancements in designing and fabricating advanced nanocellulose-based biomaterials (cellulose nanocrystals, bacterial nanocellulose and cellulose nanofibrils) that are promising for biomedical applications, and discuss materials requirement in each application, along with the challenges the materials might face. Finally, we give an overview on the future directions of the nanocellulose-based materials in biomedical field.

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    of bacterial cellulose films using plant-based natural dyes. Abstract The aim of this work was to test the use of plant-based natural dyes on bacterial cellulose (BC) to add aesthetic value to dyed pellicles while maintaining the mechanical properties. Natural pigments from Clitoria ternatea L. and Hibiscus rosa-sinensis were tested. The commercial ARAQCEL RL 500 was also used for comparison purposes. The behaviour of biocellulose regarding dye fixation, rehydration, tensile strength, and elasticity was evaluated in comparison to the dried biomaterial, showing that dyeing is a process that can be performed on hydrated BC. Dyeing the BC films through an innovative process maintained the crystallinity, thermal stability and mechanical strength of the BC and confirmed the compatibility of the membrane with the dyes tested, from the observed Scanning Electron Microscopy (SEM) morphology of nanofibers. Dyed biomaterial can be applied to various products, as confirmed by the results of the mechanical tests. As environmental awareness and public concern regarding pollution increase, the combination of natural dyes and BC pellicles can produce an attractive new material for the textile industry.
  • Chapter
    Recent advances in materials science and nanotechnology together with ecological awareness have increased the interest in the development of green products. The biomedical industry has not taken an exemption from this current trend. Nanocellulose is a green material that can be obtained from natural sources such as plants, bacteria, algae or animals; being cost-effective, eco-friendly and renewable. Nanocellulose-based composites have become of great interest in biomedical applications, given their inherent biocompatibility. Since ancient times cellulose has been used in gauzes for treatment of wounds and at present time it offers a wide range of possibilities that have been opened up by nanotechnology. Nanocellulose obtained from microorganisms has similar morphology to collagen, the major component of extracellular matrices, and its applications are diverse, ranging from scaffolds for tissue engineering, implants for cell regeneration to biosensors. By opening up the medical field to composites, nanocellulose can offer significant advantages over the traditional materials, in many biomedical applications in which nanocellulose can play an important role because of its mechanical strength. Furthermore, nanocellulose can Biomimick several tissues such as cartilage, skin, blood vessels, among others. This chapter discusses some relevant biomedical applications of nanocellulose-based composites. In the medium to long term, nanocellulose-based composites will play an important role in developing in vitro tissues and organs, accelerating healing processes and improving life quality of mankind without impacting the environment.
  • Article
    A highly efficient approach to concentrate nanocellulose suspensions is urgently required for the application of nanocellulose at a large scale. In this paper, a facile method, freeze concentration, was used to concentrate a nanocellulose slurry. This method only includes two processes, first freezing of the slurry followed by melting. Most of the water in the slurries could be easily removed, and the concentrated nanofibrils were easily redispersed. Approximately 96.1% and 94.5% of the water of bamboo pulp and hardwood pulp nanofibril slurries were removed; furthermore, the solid content increased from approximately 0.5% to 12.8% and 9.1%, respectively. These results indicate that freeze concentration is well-suited for large-scale nanocellulose concentration to facilitate transport. Graphical abstract Open image in new window
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    Full-text available
    Nanocellulose, derived from cellulose hydrolysis, has unique optical and mechanical properties, high surface area, and good biocompatibility.
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    Cellulose nanofibrils produced after quaternary amine pretreatment were investigated as basic characteristics of CNF with nanoparticle size, viscosity, and rheological properties. With DS 0.1 (C-CNF1), width of cellulose nanofibril was 8.1-14.1 nm compared with width of 3.9-9.5 nm with DS 0.3 (C-CNF2), which had narrower width distribution than carboxymethyl pretreated cellulose nanofibril (DS 0.3, width range: 3.1-20.6 nm). There was no significant difference in length of CNF regardless of pretreatment method or different degree of substitution. In viscosity, carboxymethylated CNF had higher than quaternary amine treated CNF due to different affinity to aqueous medium with different functional group. Quaternary aminated CNF had gel-like structure but there was no expulsion of water (syneresis), which syneresis is the characteristics of carboxymethylated CNF. © 2018 Korean Technical Assoc. of the Pulp and Paper Industry. All rights reserved.
  • Article
    Nanocellulose (NC) materials have some unique properties, which make them attractive as organic or inorganic supports for catalytic applications. Nanocatalysts with diameters of less than 100 nm are difficult to separate from the reaction mixture, therefore, magnetic nanoparticles (MNPs) were used as catalysts to overcome this problem. Fe3O4@NCs/BF0.2 as a green, bio‐based, eco‐friendly, and recyclable catalyst was synthesized and characterized using fourier‐transform infrared spectroscopy (FT‐IR), vibrating sample magnetometer (VSM), X‐ray diffraction (XRD), X‐ray fluorescence (XRF), Brunauer–Emmett–Teller (BET), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and thermal gravimetric analysis (TGA) techniques. Fe3O4@NCs/BF0.2 was employed for the synthesis of 2,3‐dihydro‐1H‐perimidine derivatives via a reaction of 1,8‐diaminonaphthalene with various aldehydes at room temperature under solvent‐free conditions. The present procedure offers several advantages including a short reaction time, excellent yields, easy separation of catalyst, and environmental friendliness.
  • Article
    Nanocellulose (NC) among all renewable biopolymers has proven to be one of the most applicable existing nanomaterials, attributed to its fascinating diverse range of physicochemical properties. Herein, this review presents elaborately updates on current research activities focused on developed materials with NC as bycomponent for application particularly in the field of biomedicine and wastewater remediation. A brief introduction on structural properties, production as well as surface features of NC is elucidated. Next, are highlights on usage of nanocellulosic polymeric materials in biomedicine including drug delivery systems, tissue engineering, wound dressing, medical implants and in addition, applications of NC as adsorbent in the field of environmental remediation are also outlined. This section will mainly focus on the consolidation of NC with other additives to develop flexible substrates via incorporation of new functional moieties. Finally, future perspectives as well as main challenges and impediments on working with nanocellulosic‐based materials are explored in an effort to ameliorate the development and effective usage of this nanomaterial in biomedicine and water remediation. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47878.
  • Article
    The objective of this study was to verify the effect of the hemicellulose content of commercial bleached pulps on the ease of mechanical fibrillation and on its energy consumption (EC). NaOH in concentrations of 5% with 2 h of reaction, and 10% with 1 and 2 h of reaction, was evaluated for the partial removal of hemicelluloses. Pulp fibrillation was influenced by hemicellulose removal, being less fibrillated when excessive removal occurred (in the range of 4–8.5%). Hemicellulose content in the range of 9–13% increased the water retention value (WRV) and led to nanofibrils with smaller diameter, while a stronger alkali concentration reduced the WRV. X-ray diffraction (XRD) showed that reaction time was a determining factor for the crystallinity of the samples and partial conversion of cellulose I to cellulose II in pretreatments with NaOH 10% (1 and 2 h), and was a factor that may also damage the fibrillation process. Pre-treatment with NaOH 5% for 2 h promoted energy savings for both pulps. This work demonstrated that hemicellulose content has a considerable influence on the mechanical fibrillation and is a key aspect of the balance between efficient fibrillation and the energy required for that.
  • Article
    Cellulose nanofibrils (CNFs) assemble into water‐resilient materials in the presence of multivalent counter‐ions. The essential mechanisms behind these assemblies are ion–ion correlation and specific ion effects. A network model shows that the interfibril attraction indirectly influences the wet modulus by a fourth power relationship to the solidity of the network (Ew ∝ φ4). Ions that induce both ion–ion correlation and specific ion effects significantly reduce the swelling of the films, and due to the nonlinear relationship dramatically increase the wet modulus. Herein, this network model is used to explain the elastoplastic behavior of wet films of 2,2,6,6‐tetramethylpiperidine‐1‐oxyl radical (TEMPO)‐oxidized, carboxymethylated, and phosphorylated CNFs in the presence of different counter‐ions. The main findings are that the aspect ratio of the CNFs influences the ductility of the assemblies, that the bivalency of phosphorylate ligands probably limits the formation of interfibril complexes with divalent ions, and that a higher charge density increases the friction between fibrils by increasing the short‐range attraction from ion–ion correlation and specific ion effects. These findings can be used to rationally design CNF materials for a variety of applications where wet strength, ductility, and transparency are important, such as biomaterials or substrates for bioelectronics. Cellulose nanofibrils (CNFs) assemble into water‐resilient materials in the presence of multivalent ions. The essential mechanisms behind these assemblies are ion–ion correlation and specific ion effects. In the present work, a network model is developed to explain how different types of CNFs and counter‐ions influence the elastoplastic properties of wet CNF films. The suitability as substrates for biointerfaces is discussed.
  • Article
    With the purpose of designing active patches for photodynamic therapy of melanoma, transparent and soft hydrogel membranes (HMs) have been fabricated by cation‐induced gelation of rod‐like cellulose nanocrystals (CNCs) bearing negatively charged carboxylic groups. Na+, Ca2+, Mg2+ have been used as cross‐linkers of cellulose nanocrystal (CNC). The biosafety of this material and of its precursors has been evaluated in vitro in cell cultures. Morphological changes, cell organelles integrity, and cell survival with the tetrazolium salt reduction (MTT) assay were utilized as tests of cytotoxicity. Preliminary investigation was performed by addition of the hydrogel components to the cell culture medium and by incubations of the CNC‐HM in direct and indirect contact with a confluent monolayer of A375 melanoma cells. Direct contact assays suffered from interference of physical stress. Careful evaluation of cytotoxicity was obtained considering the overall picture provided by microscopy and biochemical tests performed with the CNC‐HM in indirect contact with two melanoma cell lines (A375, M14) and human fibroblasts. CNCs have been demonstrated to be a safe precursor material and CNC‐HMs have a good biocompatibility provided that the excess of cations, in particular of Ca2+ is removed. These results indicate that CNC and can be safely used to fabricate biomedical devices such as transparent hydrogel patches, although attention must be paid to the fabrication procedure.
  • Article
    Full-text available
    Cellulose nanocrystals (CNCs) have great potential in many areas of research, applications, and future commercialization prospects. Recently, CNCs have emerged as attractive candidates for biomedical applications such as drug and gene delivery systems. As such, cytotoxicity studies have been the major focus in the past decade. However, despite the rod-like nature of CNCs, the potential immune response of surface-modified CNCs is not well investigated. The current study examined the potential immune and antioxidant response induced by CNCs grafted with β -cyclodextrin (CNCs- β -CD) in a human monocyte cell line (THP-1) and a mouse macrophage-like cell line (J774A.1). We analyzed the secretion of the proinflammatory cytokine, interleukin 1 β (IL-1 β ), by ELISA and mitochondria-derived reactive oxygen species (ROS) using fluorescence cell imaging and examined the intracellular levels of proteins involved in the immune and antioxidant response by immunoblotting. Our results indicated a dramatic increase neither in the IL-1 β secretion nor in the mitochondria-derived ROS resulting in no changes in the intracellular antioxidant response in THP-1 cells treated with different concentrations of CNCs- β -CD. Overall, CNCs- β -CD is nonimmunogenic and do not induce an increased antioxidant response under the conditions tested and hence has the potential to be used as a drug delivery carrier.
  • Article
    Epichlorohydrin has been successfully used for coupling nano metal oxides by covalent linkage. Applying this method, a highly efficient and magnetically separable catalyst was synthesized using n‐Fe3O4 and n‐TiO2. This approach is the extension of the third methodology for magnetization of nanoparticles. Stability and catalytic properties of the novel catalyst was investigated by Fourier transform infrared spectroscopy (FT‐IR), field emission scanning electron microscopy (FE‐SEM), thermogravimetric analysis (TGA), X‐ray diffraction (XRD) and vibrating sample magnetometer (VSM). Also, the catalytic activity and selectivity were tested for the oxidation reaction of sulfides to sulfoxides. The catalyst exhibited superior recyclability and reusability. It accomplished six consecutive runs, thoroughly with negligible loss of activity. The third methodology for magnetization of nanoparticles is extended by the use of a stable, economic covalent linker. The magnetization was occurred using epichlorohydrin to graft Fe3O4 to a second nano‐metal oxide. This methodology is capable of grafting each two nano‐metal oxides.
  • Article
    The treatment of disorders of the nervous system poses a major clinical challenge. Development of neuromodulation (i.e., interfacing electronics to nervous tissue to modulate its function) has provided patients with neuronal-related deficits a new tool to regain lost function. Even though, in principle, electrical stimulation and recording by interfacing technology is simple and straightforward, each presents different challenges. In stimulation, the challenge lies in targeting the effects of stimulation on precise brain regions, as each region specializes for particular functions on a millimeter scale. In practice, our experience with deep brain stimulation for treating Parkinson’s disease reveals that stimulation of larger regions of the brain can be relatively well tolerated. However, the task of fabricating an ideal electrode that performs reliably for long periods of time has been daunting. The primary obstacle in successful interfacing comes from integration of electrodes (“foreign” material) into the nervous system (biological material). The second tier of complexity is added by the need for the electrodes to “sense” signals emanating from individual neurons, an estimated microenvironment of 10 to 20 microns in diameter. Materials design and technology impact electrode design—with their size, shape, mechanical properties, and composition all being actively optimized to enable chronic, stable recordings of neural activity. The articles in this issue discuss designing interfacing technology to “listen to the nervous system” from a materials perspective. These include identification of materials with a potential for in vivo development, electrodes with various material types, including natural nanocomposites, and optical neural interfacing.
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    Prosthetic biomaterials are required to be non-toxic, non-thrombogenic, and non-immunogenic. Bacterial cellulose (BC) synthesized by Gluconacetobacter xylinus has recently been studied as a biocompatible material due to its unique features such as high purity, crystallinity, biodegradability, and tensile strength as compared to plant cellulose. Although BC has high potential to be used as biomaterial, its toxicity and immunoreactivity have not been properly studied yet. In this report, we investigated the immunoreactivity of BC in vitro in human umbilical vein endothelial cells (HUVECs) and in vivo using BALB/c mice. We report that BC does not induce apoptosis and necrosis in HUVECs and does not stimulate immune response in both HUVECs and BALB/c mice models. These results suggest that BC may be widely used as a biocompatible biomaterial for tissue engineering and biosensors.
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    Cellulose is the most abundant biomass material in nature, and possesses some promising properties, such as mechanical robustness, hydrophilicity, biocompatibility, and biodegradability. Thus, cellulose has been widely applied in many fields. "Smart" materials based on cellulose have great advantages-especially their intelligent behaviors in reaction to environmental stimuli-and they can be applied to many circumstances, especially as biomaterials. This review aims to present the developments of "smart" materials based on cellulose in the last decade, including the preparations, properties, and applications of these materials. The preparations of "smart" materials based on cellulose by chemical modifications and physical incorporating/blending were reviewed. The responsiveness to pH, temperature, light, electricity, magnetic fields, and mechanical forces, etc. of these "smart" materials in their different forms such as copolymers, nanoparticles, gels, and membranes were also reviewed, and the applications as drug delivery systems, hydrogels, electronic active papers, sensors, shape memory materials and smart membranes, etc. were also described in this review.
  • Article
    Bacterial cellulose (BC) has attracted much attention as a novel biomaterial recently. In this work, the special chemical structure, topology structure and mechanical behavior of C2, 3-oxidized dialdehyde BC (DBC) were investigated. The DBC was prepared from the selective-oxidation of BC with sodium periodate. DBC membranes show obvious shrinkage in 2D direction with no significant changes in thickness. Similar to elastins, DBC exhibits a typical nonlinear elasticity, it can return to its original shape as soon as the deformation force is removed. Similarly to elastin, DBC exhibits a typical nonlinear elastic behavior. It can return to its original shape as soon as the deformation force is removed, and this nonlinear elastic behavior is typical for fiber networks in general. DBC has a nano-fiber network topology structure that is similar to the extracellular matrix. Moreover, the reaction between cell-surface proteins and aldehydes of DBC is conducive to the adhesion and proliferation of cells within the DBC networks. In general, the nonlinear elasticity, topology structure and cell adhesion of DBC were similar to the extracellular matrix. This demonstrates the potential of using DBC as a material in the repair process of injured tissues.
  • Article
    Semi-solid materials represent an important category of inactive ingredients (excipients) of pharmaceutical products. Here we review several common semisolid polymers currently used in the controlled release formulations of many drugs. These polymers are selected based on their importance and broad scope of application in FDA-approved drug products and include several polysaccharides (cellulose, starch, chitosan, alginate) and carbomers, a group of mucoadhesive synthetic polymers. Glyceride-based polymers used in self-emulsifying drug delivery systems (SEDDS) will also be discussed for its importance in formulating poorly water-soluble drugs. Unique features and advantages of each type of semi-solid materials are discussed and examples of their use in oral delivery of drugs are provided. Finally, future prospects of developing new and better semi-solid excipients are discussed with the objective of facilitating clinical translation.
  • Article
    Biopolymer-based nanogels (bionanogels) are a promising platform as polymer-based drug delivery systems encapsulting hydrophilic anticancer therapeutics; however, enhanced/controlled drug release is highly desired. Herein, we report new dual stimuli-responsive bionanogels (ssBNGs) as potential intracellular delivery nanocarriers with multi-controlled and enhanced drug release. A facile aqueous crosslinking polymerization of oligo(ethylene oxide)-containing methacrylate (OEOMA) in the presence of carboxymethyl cellulose (CMC) and a disulfide-labeled dimethacrylate allows for the synthesis of ssBNGs crosslinked with disulfide linkages of POEOMA-grafted CMC. These ssBNGs exhibit dual response release of encapsulated anticancer drugs: reductive cleavage of disulfide crosslinks and acidic pH-response of carboxylic acid groups in CMC. Their applicability toward tumor-targeting drug delivery applications is demonstrated with confocal laser scanning microscopy for cellular uptake and cell viability, as well as a facile bioconjugation with a water-soluble UV-active dye as a model cell-targeting biomolecule.
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    To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing.
  • Article
    The influence of nanostructure on the cytocompatibility of cellulose films is analyzed providing insight into how physicochemical properties of surface modified microfibrillated cellulose (MFC) and Cladophora nanocellulose (CC) affect the materials cytocompatibility. CC is modified through TEMPO-mediated oxidation and glycidyltrimethylammonium chloride (EPTMAC) condensation to obtain anionic and cationic nanocellulose samples respectively, while anionic and cationic MFC samples are obtained by carboxymethylation and EPTMAC condensation respectively. Films of unmodified, anionic and cationic MFC and CC are prepared by vacuum filtration and characterized in terms of specific surface area, pore size distribution, degree of crystallinity, surface charge and water content. Human dermal fibroblasts are exposed to culture medium extracts of the films in an indirect contact cytotoxicity test. Moreover, cell adhesion and viability are evaluated in a direct contact assay and the effects of the physicochemical properties on cell behavior are discussed. In the indirect cytotoxicity test no toxic leachables are detected, evidencing that the CC and MFC materials are non-cytotoxic, independently of the chemical treatment that they have been subjected to. The direct contact tests show that carboxymethylated-MFC presents a more cytocompatible profile than unmodified and trimethylammonium-MFC. TEMPO-CC promotes fibroblast adhesion and presents cell viability comparable to the results obtained with the tissue culture material Thermanox. We hypothesize that the distinct aligned nanofiber structure present in the TEMPO-CC films is responsible for the improved cell adhesion. Thus, by controlling the surface properties of cellulose nanofibers, such as chemistry, charge, and orientation, cell adhesion properties can be promoted.
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    Background The challenge remains to reliably mimic human exposure to high aspect ratio nanoparticles (HARN) via inhalation. Sophisticated, multi-cellular in vitro models are a particular advantageous solution to this issue, especially when considering the need to provide realistic and efficient alternatives to invasive animal experimentation for HARN hazard assessment. By incorporating a systematic test-bed of material characterisation techniques, a specific air-liquid cell exposure system with real-time monitoring of the cell-delivered HARN dose in addition to key biochemical endpoints, here we demonstrate a successful approach towards investigation of the hazard of HARN aerosols in vitro.Methods Cellulose nanocrystals (CNCs) derived from cotton and tunicates, with differing aspect ratios (~9 and ~80), were employed as model HARN samples. Specifically, well-dispersed and characterised CNC suspensions were aerosolised using an ¿Air Liquid Interface Cell Exposure System¿ (ALICE) at realistic, cell-delivered concentrations ranging from 0.14 to 1.57 ¿g/cm2. The biological impact (cytotoxicity, oxidative stress levels and pro-inflammatory effects) of each HARN sample was then assessed using a 3D multi-cellular in vitro model of the human epithelial airway barrier at the air liquid interface (ALI) 24 hours post-exposure. Additionally, the testing strategy was validated using both crystalline (quartz (DQ12)) as a positive particulate control in the ALICE system and long fibre amosite asbestos (LFA) confirm the susceptibility of the in vitro model to a fibrous insult.ResultsA rapid (¿4 min), controlled nebulisation of CNC suspensions enabled a dose-controlled and spatially homogeneous CNC deposition onto cells cultured under ALI conditions. Real-time monitoring of the cell-delivered CNC dose with a quartz crystal microbalance was accomplished. Independent of CNC aspect ratio, no significant cytotoxicity (p¿>¿0.05), induction of oxidative stress, or (pro)-inflammatory responses were observed up to the highest concentration of 1.57 ¿g/cm2. Both DQ12 and LFA elicited a significant (p¿<¿0.05) pro-inflammatory response at sub-lethal concentrations in vitro.Conclusion In summary, whilst the present study highlights the benign nature of CNCs, it is the advanced technological and mechanistic approach presented that allows for a state of the art testing strategy to realistically and efficiently determine the in vitro hazard concerning inhalation exposure of HARN.
  • Article
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    Objective: The mechanisms underlying intracortical microelectrode encapsulation and failure are not well understood. A leading hypothesis implicates the role of the mechanical mismatch between rigid implant materials and the much softer brain tissue. Previous work has established the benefits of compliant materials on reducing early neuroinflammatory events. However, recent studies established late onset of a disease-like neurodegenerative state. Approach: In this study, we implanted mechanically-adaptive materials, which are initially rigid but become compliant after implantation, to investigate the long-term chronic neuroinflammatory response to compliant intracortical microelectrodes. Main results: Three days after implantation, during the acute healing phase of the response, the tissue response to the compliant implants was statistically similar to that of chemically matched stiff implants with much higher rigidity. However, at two, eight, and sixteen weeks post-implantation in the rat cortex, the compliant implants demonstrated a significantly reduced neuroinflammatory response when compared to stiff reference materials. Chronically implanted compliant materials also exhibited a more stable blood-brain barrier than the stiff reference materials. Significance: Overall, the data show strikingly that mechanically-compliant intracortical implants can reduce the neuroinflammatory response in comparison to stiffer systems.
  • Article
    Oxidized carboxymethyl cellulose (OCMC) was prepared by an oxidation reaction of carboxymethyl cellulose in the presence of sodium periodate. In situ crosslinked hydrogels were obtained through the crosslinking reaction between the active aldehyde of OCMC and the amino groups of the carboxymethyl chitosan (CMCS). The structure of the hydrogels was characterized by FTIR and scanning electron microscopy. Gelation time test showed that the hydrogel had the shortest gelation time of 24 s. The equilibrium fluid content, which represented the swelling degree, was evaluated and we found that the pH increased from 3.0 to 9.0, the equilibrium fluid content increased, and the highest equilibrium fluid content reached 312.83% as pH = 9.0. The wound healing efficacy of the hydrogel was evaluated in experimental deep second degree burns using a rat model. Results indicated that the wound covered with hydrogel was completely filled with new epithelium within 2 weeks, without any significant adverse reactions. The in situ crosslinked hydrogel fulfilled many critical elements in a wound dressing material. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
  • Article
    A cost-effective and energy-saving approach to prepare microfibrillated cellulose (MFC) nanocomposites from natural wood fibers is reported. The MFC was mixed with calcium peroxide (CPO) with or without catalase to form multilayered MFC nanocomposites that allow modulation of the releases of hydrogen peroxide (H2O2) or oxygen (O2), respectively. The release profile of H2O2 from the MFC nanocomposites up to five days was obtained, and the effects of H2O2 and O2 on the responses of mammalian cells were evaluated. The results showed that MFC itself possesses great biocompatibility, and the MFC/CPO nanocomposites are able to suppress cell proliferation. The further addition of catalase into the MFC/CPO composites converts H2O2 to O2 so effectively that enhanced L-929 fibroblasts cell density was clearly found. The as-prepared MFC/CPO and [MFC+catalase]/CPO nanocomposites were shown to be applicable on alternative substrates and revealed similar functions. Moreover, the cell cultured on the [MFC+catalase]/CPO composites under a serum-free condition revealed that the generation of oxygen plays a role in supporting cell proliferation. This study is among the first work to report the modulation of the release of H2O2 and O2 by using microfibril cellulose-based materials for applications in wound sterilization and to accelerate wound healing.
  • Article
    The capability to deliver light to specific locations within the brain using optogenetic tools has opened up new possibilities in the field of neural interfacing. In this context, optical fibers are commonly inserted into the brain to activate or mute neurons using photosensitive proteins. While chronic optogenetic stimulation studies are just beginning to emerge, knowledge gathered in connection with electrophysiological implants suggests that the mechanical mismatch of conventional optical fibers and the cortical tissue may be a significant contributor to neuroinflammatory response. Here, we present the design and fabrication of physiologically responsive, mechanically adaptive optical fibers made of poly(vinyl alcohol) (PVA) that may mitigate this problem. Produced by a one-step wet-spinning process, the fibers display a tensile storage modulus E′ of ∼7000 MPa in the dry state at 25°C and can thus readily be inserted into cortical tissue. Exposure to water causes a drastic reduction of E′ to ∼35 MPa on account of modest swelling with the water. The optical properties at 470 and 590 were comparable with losses of 0.7±0.04 dB/cm at 470 nm and 0.6±0.1 dB/cm at 590 nm in the dry state and 1.1±0.1 dB/cm at 470 nm and 0.9±0.3 dB/cm at 590 nm in the wet state. The dry end of a partially switched fiber with a length of 10 cm was coupled with a light-emitting diode with an output of 10.1 mW to deliver light with a power density of >500 mW/cm2 from the wet end, which is more than sufficient to stimulate neurons in vivo. Thus, even without a low-refractive index cladding, the physiologically responsive, mechanically adaptive optical fibers presented here appear to be a very useful new tool for future optogenetic studies.
  • Article
    This work describes the measurement and comparison of several important properties of native cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs), such as crystallinity, morphology, aspect ratio, and surface chemistry. Measurement of the fundamental properties of seven different CNCs/CNFs, from raw material sources (bacterial, tunicate, and wood) using typical hydrolysis conditions (acid, enzymatic, mechanical, and 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-mediated oxidation), was accomplished using a variety of measurement methods. Atomic force microscopy (AFM), transmission electron microscopy (TEM), and (13)C cross-polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR) spectroscopy were used to conclude that CNCs, which are rodlike in appearance, have a higher crystallinity than CNFs, which are fibrillar in appearance. CNC aspect ratio distributions were measured and ranged from 148 ± 147 for tunicate-CNCs to 23 ± 12 for wood-CNCs. Hydrophobic interactions, measured using inverse gas chromatography (IGC), were found to be an important contribution to the total surface energy of both types of cellulose. In all cases, a trace amount of naturally occurring fluorescent compounds was observed after hydrolysis. Confocal and Raman microscopy were used to confirm that the fluorescent species were unique for each cellulose source, and demonstrated that such methods can be useful for monitoring purity during CNC/CNF processing. This study reveals the broad, tunable, multidimensional material space in which CNCs and CNFs exist.
  • Article
    Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis.
  • Article
    Recently, cellulose nanowhiskers have attracted attention as a promising material in the biomedical field because of their outstanding properties such as hydrophilicity, biocompatibility, biodegradability, and high surface area. In this work, we prepared a novel nanometric carrier molecule for amine-containing biologically active molecules and drugs employing functionalized cellulose nanowhiskers. The nanowhiskers were grafted with a spacer molecule, gamma aminobutyric acid, using a periodate oxidation and Schiff's base condensation reaction sequence. To achieve controlled and rapid delivery of the targeting moiety, syringyl alcohol, a releasable linker, was then attached to it. All the reactions were carried out in aqueous media and the resulting products were characterized by FT-IR, NMR, XPS, and TEM experiments to evaluate the functional groups, structure, and morphology respectively.
  • Article
    Polymers derived from plant (polysaccharides) and animal (proteins) kingdoms have been widely used for a variety of biomedical applications including drug delivery and tissue regeneration. These polymers due to their biochemical similarity with human extracellular matrix components are readily recognized and accepted by the body. Natural polymers inherit numerous advantages including natural abundance, relative ease of isolation, and room for chemical modification to meet varying technological needs. In addition, these polymers undergo enzymatic and/or hydrolytic degradation in biologic environments into non-toxic degradation byproducts. Polysaccharides (carbohydrates) are often isolated and purified from renewable sources including plants, animals, and microorganisms. Majority of these polymers are found in the extracellular matrix components of organisms and participate in inter and intracellular cell signaling and contribute to their growth. All these features offer polysaccharide-based biomaterials much desired biological recognition, biocompatibility, and bioactivity. In spite of many merits as biomaterials, these polysaccharides suffer from drawbacks including variations in material properties based on source, microbial contamination, uncontrolled water uptake, poor mechanical strength, and unpredictable degradation patterns. These inconsistencies have limited the usage of polysaccharides and biomedical application related technology development. Many of these polysaccharides have been chemically modified to achieve consistent physicochemical properties including mechanical stability, degradation, and bioactivity and processed into microparticles, hydrogels, and 3D porous structures for tissue regeneration applications. Presence of multiple functionalities on the polymer backbone allows easy structure modifications for the required application. The current article focuses on the application of polysaccharide-based materials in regenerative engineering and delivery. Copyright © 2014 John Wiley & Sons, Ltd.
  • Article
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    Taxanes are a class of anticancer agents with a broad spectrum and have been widely used to treat a variety of cancer. However, its long term use has been hampered by accumulating toxicity and development of drug resistance. The most extensively reported mechanism of resistance is the overexpression of P-glycoprotein (Pgp). We have developed a PEGylated carboxymethylcellulose conjugate of docetaxel (Cellax), which condenses into ~120 nm nanoparticles. Here we demonstrated that Cellax therapy did not upregulate Pgp expression in MDA-MB-231 and EMT-6 breast tumor cells whereas a significant increase in Pgp expression was measured with native docetaxel (DTX) treatment. Treatment with DTX led to 4 to 7-fold higher Pgp mRNA expression and 2-fold higher Pgp protein expression compared to Cellax treatment in the in vitro and in vivo system respectively. Cellax also exhibited significantly increased efficacy compared to DTX in a taxane-resistant breast tumor model. Against the highly Pgp expressing EMT6/AR1 cells, Cellax exhibited a 6.5 times lower IC50 compared to native DTX, and in the in vivo model, Cellax exhibited 90% tumor growth inhibition, while native DTX had no significant antitumor activity.
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    The cellular and molecular mechanism by which neuroinflammatory pathways respond to and propagate the reactive tissue response to intracortical microelectrodes remains an active area of research. We previously demonstrated that both, the mechanical mismatch between rigid implants and the much softer brain tissue, as well as oxidative stress contribute to the neurodegenerative reactive tissue response to intracortical implants. In this study, we utilize physiologically-responsive, mechanically-adaptive polymer implants based on poly(vinyl alcohol), with the capability to also locally administer the anti-oxidant curcumin. The goal of this study is to investigate if the combination of two independently effective mechanisms - softening of the implant and anti-oxidant release - leads to synergistic effects in vivo. Over the first four weeks of the implantation, curcumin-releasing, mechanically-adaptive implants were associated with higher neuron survival and a more stable blood-brain barrier at the implant-tissue interface than the neat poly(vinyl alcohol) controls. Twelve weeks post implantation, the benefits of the curcumin release were lost, and both sets of compliant materials (with and without curcumin) had no statistically significant differences in neuronal density distribution profiles. Overall, however, the curcumin-releasing softening polymer implants cause minimal implant-mediated neuroinflammation, and embody the new concept of localized drug delivery from mechanically-adaptive intracortical implants.
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    Natural polymers such as collagens, elastin, and fibrinogen make up much of the body’s native extracellular matrix (ECM). This ECM provides structure and mechanical integrity to tissues, as well as communicating with the cellular components it supports to help facilitate and regulate daily cellular processes and wound healing. An ideal tissue engineering scaffold would not only replicate the structure of this ECM, but would also replicate the many functions that the ECM performs. In the past decade, the process of electrospinning has proven effective in creating non-woven ECM analogue scaffolds of micro to nanoscale diameter fibers from an array of synthetic and natural polymers. The ability of this fabrication technique to utilize the aforementioned natural polymers to create tissue engineering scaffolds has yielded promising results, both in vitro and in vivo, due in part to the enhanced bioactivity afforded by materials normally found within the human body. This review will present the process of electrospinning and describe the use of natural polymers in the creation of bioactive ECM analogues in tissue engineering.
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    The dermis in the holothurian body wall is a typical catch connective tissue or mutable collagenous tissue that shows rapid changes in stiffness. Some chemical factors that change the stiffness of the tissue were found in previous studies, but the molecular mechanisms of the changes are not yet fully understood. Detection of factors that change the stiffness by working directly on the extracellular matrix was vital to clarify the mechanisms of the change. We isolated from the body wall of the sea cucumber Stichopus chloronotus a novel protein, softenin, that softened the body-wall dermis. The apparent molecular mass was 20 kDa. The N-terminal sequence of 17 amino acids had low homology to that of known proteins. We performed sequential chemical and physical dissections of the dermis and tested the effects of softenin on each dissection stage by dynamic mechanical tests. Softenin softened Triton-treated dermis whose cells had been disrupted by detergent. The Triton-treated dermis was subjected to repetitive freeze-and-thawing to make Triton-Freeze-Thaw (TFT) dermis that was softer than the Triton-treated dermis, implying that some force-bearing structure had been disrupted by this treatment. TFT dermis was stiffened by tensilin, a stiffening protein of sea cucumbers. Softenin softened the tensilin-stiffened TFT dermis while it had no effect on the TFT dermis without tensilin treatment. We isolated collagen from the dermis. When tensilin was applied to the suspending solution of collagen fibrils, they made a large compact aggregate that was dissolved by the application of softenin or by repetitive freeze-and-thawing. These results strongly suggested that softenin decreased dermal stiffness through inhibiting cross-bridge formation between collagen fibrils; the formation was augmented by tensilin and the bridges were broken by the freeze-thaw treatment. Softenin is thus the first softener of catch connective tissue shown to work on the cross-bridges between extracellular materials.
  • Article
    There is growing evidence that filamentous nanoparticles offer advantages over spherical ones in drug delivery applications. The purpose of this study was to assess the potential of rod-like, plant-derived cellulose nanocrystals (CNCs) for nanomedical uses. Besides a nonspherical morphology, their facile bioconjugation, surface hydrophilicity and small size render CNCs promising drug carriers. The cytotoxicity of CNCs against nine different cell lines (HBMEC, bEnd.3, RAW 264.7, MCF-10A, MDA-MB-231, MDA-MB-468, KB, PC-3 and C6) was determined by MTT and LDH assay. CNCs showed no cytotoxic effects against any of these cell lines in the concentration range and exposure time studied (0–50 μg/mL and 48 h, respectively). Cellular uptake of fluorescein-5′-isothiocyanate-labeled CNCs by these cell lines, quantified with a fluorescence microplate reader, was minimal. The lack of cytotoxicity and the low nonspecific cellular uptake support our hypothesis that CNCs are good candidates for nanomedical applications.
  • Article
    The recording of neural signals with microelectrodes that are implanted into the cortex of the brain is potentially useful for a range of clinical applications. However, the widespread use of such neural interfaces has so far been stifled because existing intracortical electrode systems rarely allow for consistent long-term recording of neural activity. This limitation is usually attributed to scar formation and neuron death near the surface of the implanted electrode. It has been proposed that the mechanical property mismatch between existing electrode materials and the brain tissue is a significant contributor to these events. To alleviate this problem, we utilized the architecture of the sea cucumber dermis as a blueprint to engineer a new class of mechanically adaptive materials as substrates for “smart” intracortical electrodes. We demonstrated that these originally rigid polymer nanocomposites soften considerably upon exposure to emulated physiological and in vivo conditions. The adaptive nature of these bioinspired materials makes them useful as a basis for electrodes that are sufficiently stiff to be easily implanted and subsequently soften to better match the stiffness of the brain. Initial histological evaluations suggest that mechanically adaptive neural prosthetics can more rapidly stabilize neural cell populations at the device interface than rigid systems, which bodes well for improving the functionality of intracortical devices.
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    An environmentally friendly approach was implemented for the production of nanocomposites with bactericidal activity, using bacterial cellulose (BC) nanofibers and chitin nanocrystals (ChNCs). The antibacterial activity of ChNCs prepared by acid hydrolysis, TEMPO-mediated oxidation or partial deacetylation of α-chitin powder was assessed and the structure of the ChNC nanoparticles was characterized by X-ray diffraction, atomic force microscopy, and solid-state 13C-NMR. The partially deacetylated ChNCs (D-ChNC) showed the strongest antibacterial activity, with 99 ± 1% inhibition of bacterial growth compared to control samples. Nanocomposites were prepared from BC nanofibers and D-ChNC by (i) in situ biosynthesis with the addition of D-ChNC nanoparticles in the culture medium of Acetobacter aceti, and (ii) post-modification by mixing D-ChNC with disintegrated BC in an aqueous suspension. The structure and mechanical properties of the BC/D-ChNC nanocomposites were characterized by Fourier transform infrared spectroscopy, elemental analysis, field-emission scanning electron microscopy, and an Instron universal testing machine. The bactericidal activity of the nanocomposites increased with the D-ChNC content, with a reduction in bacterial growth by 3.0 log units when the D-ChNC content was 50%. D-ChNC nanoparticles have great potential as substitutes for unfriendly antimicrobial compounds such as heavy metal nanoparticles and synthetic polymers to introduce antibacterial properties to cellulosic materials.
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    Curcumin, a greatly potent, non-toxic and naturally existing bioactive material in turmeric is widely employed to develop biomedical functional materials due to its environmental friendly nature. In general, curcumin functional materials were prepared by administrating non-aqueous solvents as a dissolving medium for curcumin. These non-aqueous solvents cause adverse effects for the environment and humans. However, if the curcumin functional materials are developed based on aqueous solution then the adverse effects can be eliminated. In view of this, for the first time aqueous based nanocurcumin (nanoparticles of curcumin) impregnated gelatin cellulose fibers (NCGCFs) were developed by a green process. The required nanocurcumin was prepared by ultrasonication process. Transmission electron microscopy showed the sizes of nanocurcumin exist in the range �2 to 15 nm. Nuclear magnetic resonance spectra showed no structural modification of nanocurcumin to that of curcumin. The developed fibres were characterized by fourier transform infrared spectroscopy, scanning electron microscopy, thermal analysis and swelling studies. Cumulative releasing studies showed slow and sustained releasing patterns for NCGCFs. A comparative antimicrobial study was performed for nanocurcumin impregnated gelatin cellulose fibres (NCGCFs) and curcumin impregnated gelatin cellulose fibres (CGCFs) against E. coli and S. aureus. The results indicated the superior performance of NCGCFs over CGCFs. Hence, NCGCFs prepared completely from naturally available materials can be considered as a novel kind of functional materials for wound dressing and antimicrobial applications.
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    Establishing a biology-device interface might enable the interaction between microelectronics and biotechnology. In this study, electroactive hydrogels have been produced using bacterial cellulose (BC) and conducting polymer (CP) deposited on the BC hydrogel surface to cover the BC fibers. The structures of these composites thus have double networks, one of which is a layer of electroactive hydrogels combined with BC and CP. The electroconductivity provides the composites with capabilities for voltage and current response, and the BC hydrogel layer provides good biocompatibility, biodegradability, bioadhesion and mass transport properties. Such a system might allow selective biological functions such as molecular recognition and specific catalysis and also for probing the detailed genetic and molecular mechanisms of life. A BC-CP composite hydrogel could then lead to a biology-device interface. Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) are used here to study the composite hydrogels' electroactive property. BC-PAni and BC-PPy respond to voltage changes. This provides a mechanism to amplify electrochemical signals for analysis or detection. BC hydrogels were found to be able to support the growth, spreading and migration of human normal skin fibroblasts without causing any cytotoxic effect on the cells in the cell culture. These double network BC-CP hydrogels are biphasic Janus hydrogels which integrate electroactivity with biocompatibility, and might provide a biology-device interface to produce implantable devices for personalized and regenerative medicine.
  • Article
    Injectable hydrogels based on carboxymethyl cellulose and dextran, reinforced with rigid rod-like cellulose nanocrystals (CNCs) and aldehyde-functionalized CNCs (CHO-CNCs), were prepared and characterized. The mechanical properties, internal morphology, and swelling of injectable hydrogels with unmodified and modified CNCs at various loadings were examined. In all cases, gelation occurred within seconds as the hydrogel components were extruded from a double-barrel syringe, and the CNCs were evenly distributed throughout the composite, as observed by scanning and transmission electron microscopy. When immersed in purified water or 10 mM PBS, all CNC-reinforced hydrogels maintained their original shape for more than 60 days. The maximum storage modulus was observed in hydrogels with 0.250 wt % of unmodified CNCs and 0.375 wt % of CHO-CNCs. CHO-CNCs acted as both a filler and a chemical cross-linker, making the CHO-CNC-reinforced hydrogels more elastic, more dimensionally stable, and capable of facilitating higher nanoparticle loadings compared to hydrogels with unmodified CNCs, without sacrificing mechanical strength. No significant cytotoxicity to NIH 3T3 fibroblast cells was observed for the hydrogels or their individual components. These properties make CNC-reinforced injectable hydrogels of potential interest for various biomedical applications such as drug delivery vehicles or tissue engineering matrices.
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    Cellulose macro- and nanofibers have gained increasing attention due to the high strength and stiffness, biodegradability and renewability, and their production and application in development of composites. Application of cellulose nanofibers for the development of composites is a relatively new research area. Cellulose macro- and nanofibers can be used as reinforcement in composite materials because of enhanced mechanical, thermal, and biodegradation properties of composites. Cellulose fibers are hydrophilic in nature, so it becomes necessary to increase their surface roughness for the development of composites with enhanced properties. In the present paper, we have reviewed the surface modification of cellulose fibers by various methods. Processing methods, properties, and various applications of nanocellulose and cellulosic composites are also discussed in this paper.
  • Article
    Bacterial cellulose has been demonstrated to be a remarkably versatile biomaterial and widely used in biomedical applications due to its unique physical properties. Here we reported for the first time a "living membrane" system based on recombinant Escherichia coli bacterial strains entrapped in cellulosic membranes produced by Gluconacetobacter xylinus. Biologically driven detection and identification of a range of target molecules presents unique challenges, and requires that detection methods are developed to be rapid, specific and sensitive. The compatibility of G. xylinus and recombinant E. coli strains was first investigated for co-cultivation, and the relationship between the number of entrapped E. coli and the level of inducible signal achieved was further explored by fluorescent signal observation in confocal microscopy. Finally to amplify the response to inducers for maximum fluorescent signal, a positive-feedback genetic amplifier was designed within recombinant E. coli strain entrapped in the living cellulosic membrane system, allowing for the detection mechanism to be extremely sensitive and resulting in a significant fluorescent signal from a single receptor binding event. The living membrane system proposed here will create devices of greater complexity in function for applications in biological and chemical detection.
  • Article
    Here, the layer-by-layer method was applied to assemble films from chitosan paired with either heparin or a semisynthetic cellulose sulfate (CS) that possessed a higher sulfation degree than heparin. Ion pairing was exploited during multilayer formation at pH 4, while hydrogen bonding is likely to occur at pH 9. Effects of polyanions and pH value during layer formation on multilayers properties were studied by surface plasmon resonance ("dry layer mass"), quartz crystal microbalance with dissipation monitoring ("wet layer mass"), water contact angle, and zeta potential measurements. Bioactivity of multilayers was studied regarding fibronectin adsorption and adhesion/proliferation of C2C12 myoblast cells. Layer growth and dry mass were higher for both polyanions at pH 4 when ion pairing occurred, while it decreased significantly with heparin at pH 9. By contrast, CS as polyanion resulted also in high layer growth and mass at pH 9, indicating a much stronger effect of hydrogen bonding between chitosan and CS. Water contact angle and zeta potential measurements indicated a more separated structure of multilayers from chitosan and heparin at pH 4, while CS led to a more fuzzy intermingled structure at both pH values. Cell behavior was highly dependent on pH during multilayer formation with heparin as polyanion and was closely related to fibronectin adsorption. By contrast, CS and chitosan did not show such dependency on pH value, where adhesion and growth of cells was high. Results of this study show that CS is an attractive candidate for multilayer formation that does not depend so strongly on pH during multilayer formation. In addition, such multilayer system also represents a good substrate for cell interactions despite the rather soft structure. As previous studies have shown specific interaction of CS with growth factors, multilayers from chitosan and CS may be of great interest for different biomedical applications.
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    This article reviews the recent trends, developments, and future applications of bio-based polymers produced from renewable resources. Bio-based polymers are attracting increased attention due to environmental concerns and the realization that global petroleum resources are finite. Bio-based polymers not only replace existing polymers in a number of applications but also provide new combinations of properties for new applications. A range of bio-based polymers are presented in this review, focusing on general methods of production, properties, and commercial applications. The review examines the technological and future challenges discussed in bringing these materials to a wide range of applications, together with potential solutions, as well as discusses the major industry players who are bringing these materials to the market. Electronic supplementary material The online version of this article (doi:10.1186/2194-0517-2-8) contains supplementary material, which is available to authorized users.
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    In nature, a number of nanocomposites are formed through biomineralization-relevant processes under mild conditions. In the present study, a total “biologic” route to fabricate nanocomposite is reported. Non-pathogenic bacteria, Gluconacetobacter xylinum, was utilized as a versatile biofactory, which produced biopolymer bacterial cellulose (BC) and induced the formation of Ag/AgCl nanoparticles, yielding BC–Ag/AgCl nanocomposite. Scanning electron microscopy revealed that nanoparticles with average size of 17.4 nm were randomly embedded into the BC network; transmission electron microscopy and X-ray diffraction confirmed that the nanoparticles were mixtures of face-centered cubic silver and silver chloride nanoparticles. Moreover, the content of silver in the BC nanocomposite is around 0.05 wt%, determined by atomic absorption spectrometry and X-ray photoelectron spectroscopy analysis. The entire process of nanocomposite fabrication was conducted at ambient environment without utilizing toxic agents or producing hazardous products, which is not only environmentally friendly but also with less chances to generate harmful products to human bodies as biomedical materials. The resultant nanocomposite displayed the desirable activity in inhibiting bacterial growth of both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli microorganisms on agar plate and in liquid culture, indicating the potential of the material as antimicrobial wound dressing materials. This work demonstrated the feasibility of using microorganism to fabricate nanocomposite, especially for biomedical materials.
  • Article
    The aim of this study was to synthesize a new antibacterial and chelating biopolymer and to evaluate its germicidal activity and its ability in metal ions removal from aqueous solutions. The material was prepared via esterification of hemp with 2-benzyl-4-chlorophenol, a germicide agent, that was covalently coupled to cellulose backbone of hydrophilic fibers by a heterogeneous synthesis, to produce a functionalized biopolymer with a satisfactory degree of substitution. The obtained biopolymer was characterized by infrared spectroscopy and differential scanning calorimetry. Its antibacterial activity in inhibiting Staphylococcus aureus and Pseudomonas aeruginosa growth in Petri dishes, was evaluated. The results suggested that this biomaterial possesses an excellent in vitro antibacterial activity and so it can be efficiently employed in biomedical fields to ensure a protection against contaminations. On the other hand, the functionalized biopolymer interacts with metal ions thanks to its chelating functional groups. The absorption capacity for a selected metal ion such as Cd(II), was investigated in aqueous solution at pH 0.65, 4.1 and 7.0 by optical emission spectroscopy. This study showed that the new system is very effective in chelating cadmium ions showing the maximum efficiency at pH 4.1. This feature makes the synthesized biomaterial a potential candidate for metal ions removal. Graphical Abstract Hemp fiber (Cannabis sativa L.) derivatives with antibacterial and chelating properties. Roberta Cassano, Sonia Trombino, Teresa Ferrarelli, Fiore Pasquale Nicoletta, Maria Vittoria Mauro, Cristina Giraldi, Nevio Picci
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    Cellulose nanofibrils based on wood pulp fibres are most promising for biomedical applications. Bacterial cellulose has been suggested for some medical applications and is presently used as wound dressing. However, cost-efficient processes for mass production of bacterial cellulose are lacking. Hence, fibrillation of cellulose wood fibres is most interesting, as the cellulose nanofibrils can efficiently be produced in large quantities. However, the utilization of cellulose nanofibrils from wood requires a thorough verification of its biocompatibility, especially with fibroblast cells which are important in regenerative tissue and particularly in wound healing. The cellulose nanofibril structures used in this study were based on Eucalyptus and Pinus radiata pulp fibres. The nanofibrillated materials were manufactured using a homogenizer without pre-treatment and with 2,2,6,6-tetramethylpiperidine-1-oxy radical as pre-treatment, thus yielding nanofibrils low and high level of anionic charge, respectively. From these materials, two types of nanofibril-based structures were formed; (1) thin and dense structures and (2) open and porous structures. Cytotoxicity tests were applied on the samples, which demonstrated that the nanofibrils do not exert acute toxic phenomena on the tested fibroblast cells (3T3 cells). The cell membrane, cell mitochondrial activity and the DNA proliferation remained unchanged during the tests, which involved direct and indirect contact between the nano-structured materials and the 3T3 cells. Some samples were modified using the crosslinking agent polyethyleneimine (PEI) or the surfactant cetyl trimethylammonium bromide (CTAB). The sample modified with CTAB showed a clear toxic behaviour, having negative effects on cell survival, viability and proliferation. CTAB is an antimicrobial component, and thus this result was as expected. The sample crosslinked with PEI also had a significant reduction in cell viability indicating a reduction in DNA proliferation. We conclude that the neat cellulose nanostructured materials tested in this study are not toxic against fibroblasts cells. This is most important as nano-structured materials based on nanofibrils from wood pulp fibres are promising as substrate for regenerative medicine and wound healing.
  • Article
    We develop an antimicrobial active robust metal-cellulose nanohybrid by covalent assembly of metal nanoparticles on cellulose fabric using a simple impregnation of thiol-modified cellulose fabric in colloidal silver (Ag) or palladium (Pd) nanoparticle solutions. The combined results of high resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDXS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) reveal that the nanoparticles are highly loaded and dispersed in the thiol-modified cellulose fabric, and X-ray photoelectron spectroscopy (XPS) analysis reveals that the nanoparticles are immobilized in the fabric by a strong and stable covalent bond with thiol functional group. This robust covalent linkage between the nanoparticles and the fabric leads to a remarkable suppression of the release of metal nanoparticles from the fabric. In addition, the metal-cellulose nanohybrids show high antimicrobial activity in excess of 99.9 % growth inhibition of the microorganism. Thus, we anticipate that our metal-cellulose nanohybrid may not only protect cell damage caused by penetration and fixation of metal nanoparticles into the human body but also act as a sustainable biomedical textile.
  • Article
    The hypothesis advanced in this issue of CELLULOSE [Springer] by Bjorn Lindman, which asserts that the solubility or insolubility characteristics of cellulose are significantly based upon amphiphilic and hydrophobic molecular interactions, is debated by cellulose scientists with a wide range of experiences representing a variety of scientific disciplines. The hypothesis is based on the consideration of some fundamental polymer physicochemical principles and some widely recognized inconsistencies in behavior. The assertion that little-recognized (or under-estimated) hydrophobic interactions have been the reason for a tardy development of cellulose solvents provides the platform for a debate in the hope that new scientific endeavors are stimulated on this important topic.
  • Article
    The study of particles on surfaces is extremely important in many area of human endeavor (ranging from microelectronics to optics to biomedical). However, the topics of review articles on nano- and microparticles are limited to the synthesis, applications and particles on the flat surface, although interest in nano- and microparticles/soft-fibrous template composites has increased because they have merits of low particle aggregation at high concentrations, good physicochemical properties, and highly mechanical strength. Here, we briefly review the recent applications of nano- and microparticles/soft-fibrous template composites such as fibrous scaffolds for bone tissue engineering, smart fibrous magnets, photoluminescence composites, and sequestration of toxic materials in water and air.
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    Novel superabsorbant cellulose–lignin hydrogels (CL) were prepared by a new two-step procedure consisting in dissolving cellulose in an alkaline solution with further mixing with lignin, followed by the chemical crosslinking with epichlorohydrin. The crosslinking occurrence was verified by Fourier Transform Infrared spectroscopy (FT-IR). The effect of the structure features of cellulose–lignin hydrogels on their dehydration heat was evaluated by Differential Scanning Calorimetry (DSC). The Scanning Electron Microscopy (SEM) images reveal some morphological aspects of the hydrogels. The degree as well as the rate of swelling in a mixture of water:ethanol=19:1 were estimated. The possible application of these hydrogels as controlled release systems was tested. Polyphenols known as having a wide range of biological effects were selected to be incorporated in such hydrogels by an optimal procedure. The extract of grapes seeds from the Chambourcin type was used as a source of polyphenols (PF). The amount of the incorporated polyphenols was estimated by UV–VIS measurements. Characterization of the hydrogels containing polyphenols was performed by FTIR spectroscopy. Some parameters were estimated based on the registered spectra, as H-bond energy (EH), the asymmetric index (a/b) and the enthalpy of H-bond formation (ΔH). The modifications of the thermal behavior and morphology induced by the presence of the polyphenols in hydrogels were highlighted by DSC and SEM, respectively. The release of polyphenols from CL hydrogels depended on the lignin content from matrices, as assessed by spectral studies. Both loading with polyphenols and their release can be controlled by the composition of the hydrogels. The kinetic of polyphenols release was studied.
  • Article
    Bionanocomposites with the combination of natural polymers and inorganic nanoparticles may induce unique properties and exhibit promising functions for different applications. Herein, we report a hydrothermal route to the preparation of cellulose/CaCO3 bionanocomposites using the cellulose solution, Ca(NO3)2·4H2O and Na2SiO3·9H2O. The cellulose solution was previously prepared by the dissolution of microcrystalline cellulose in NaOH–urea aqueous solution. The urea also acts as the CO32− source for the synthesis of CaCO3. The influences of several reaction parameters, such as the heating time, the heating temperature, and the types of additives on the products were investigated by X-ray powder diffraction, Fourier transform infrared spectrometry, scanning electron microscopy, thermogravimetric analysis, and differential thermal analysis. The experimental results demonstrated that the hydrothermal conditions had an effect on the morphology of the bionanocomposites. Cytotoxicity experiments indicated that the cellulose/CaCO3 bionanocomposites had good biocompatibility, so that the bionanocomposites could be ideal candidate for practical biomedical applications.
  • Article
    Highly porous three-dimensional scaffolds made of biopolymers are of great interest in tissue engineering applications. A novel scaffold composed of pectin, carboxymethyl cellulose (CMC) and microfibrillated cellulose (MFC) were synthesised using lyophilisation technique. The optimised scaffold with 0.1% MFC, C(0.1%), showed highest compression modulus (∼3.987MPa) and glass transition temperature (∼103°C). The pore size for the control scaffold, C(0%), was in the range of 30-300μm while it was significantly reduced to 10-250μm in case of C(0.1%). Using micro computed tomography, the porosity of C(0.1%) was estimated to be 88%. C(0.1%) showed excellent thermal stability and lower degradation rate compared to C(0%). The prepared samples were also characterised using XRD and FTIR. C(0.1%) showed controlled water uptake ability and in vitro degradation in PBS. It exhibited highest cell viability on NIH3T3 fibroblast cell line. These results suggest that these biocompatible composite scaffolds can be used for tissue engineering applications.
  • Article
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    To investigate the potential application of microcrystal cellulose (MCC) and cellulose whisker (CW) in the electrospun vascular tissue scaffolds, cellulose acetate (CA) and cellulose composite scaffolds containing MCC and CW were electrospun from CA solutions and deacetylation. Structure and morphology of MCC, CW and the fibrous composite scaffolds were investigated using FT-IR, SEM, TEM and AFM. The wettability of the scaffolds was evaluated by water contact angle analysis. The effect of MCC and CW on the biocompatibility of the scaffolds for vascular smooth muscle cells (VSMC) was assayed by MTT test, fluorescent imaging and SEM. The biocomposite scaffolds displayed multi-scaled structure and morphology. The scaffolds containing MCC and CW simultaneously exhibited significantly higher cell viability compared to those with only MCC or CW and no filler. Cell viability and morphology within the scaffolds become better with increasing content of MCC and CW. The composite scaffolds with both micro- and nano-scale organization could mimic the native extracellular matrix more closely, and further produce synergistic enhancement on VSMC viability, adhesion and proliferation. This study provides the potential applications of renewable cellulose-based particulates in biomedical field.
  • Article
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    Ultra-fine nanofiber mats of cellulosic polymer and polyvinyl alcohol (PVA) containing silver (Ag) nanoparticles were fabricated using the electrospinning technique. Polymers with hydroxyl groups on the backbone such as PVA, PVA/dextran and PVA/methyl cellulose were chosen for this study. All polymers showed the ability to reduce silver nitrate (AgNO3) to Ag-nanoparticles. To make crosslinkable networks of the water soluble polymers, the photo-crosslinkable glycidyl methacrylate moiety was attached to the hydroxyl groups of the designed macromers. AgNO3 and cytocompatible initiator (IRGACURE 2959) were added to the methacrylated polymeric solution mixture before electrospinning. The fiber morphology of the resultant nanofiber was characterised using scanning electron microscopy (SEM) and an average diameter in the range of 300 to 500 nm was observed. The resultant nanofibers containing Ag-ions and initiators were crosslinked under photoirradiation at a wavelength of 365 nm for 6 h and heated at 100 °C for 6 h for complete reduction of Ag-ions into Ag-nanoparticles. Transmission electron microscopy (TEM) analysis revealed that the Ag-nanoparticles with an average diameter of 10 to 20 nm were uniformly distributed throughout the nanofibers and its presence was confirmed using X-ray diffraction analysis. The effect of Ag-nanoparticles on the microcrystalline structure of the polymer was studied by thermal and mechanical properties analysis. The biocompatibility of the methacrylated macromers was investigated using human lung fibroblasts (IMR-90) and no cytotoxic effects were found after 4 days of incubation. The antimicrobial activity of the PVA nanofiber containing Ag-nanoparticles was tested against Escherichia coli. The nanofiber containing Ag-nanoparticles may have potential applications in biomedical devices which will be explored in the near future.
  • Article
    Using an improved method, the multilayer fermentation method, bacterial cellulose (BC) was produced by Gluconacetobacter xylinus. The structure and morphology were analysed by an electronic microscope. The surface area and tensile strength were characterised. In vitro, the cytotoxicity of BC was determined by the proliferation, adhesion property, morphology, and viability of human adipose-derived stem cells (hASCs). Full-thickness skin wounds were made on the backs of 35 mice. The wounds were subsequently treated with two types of gauzes, two types of BC films, and three types of skin grafts using 5 mice per group, respectively. The improved method was reproducible and more efficient to control the thickness and homogeneity of BC. Low cytotoxicity of the BC film and good proliferation of hASCs on the BC film were observed. Histological examinations demonstrated significant fresh tissue regeneration and capillary formation in the wound area in the BC groups on day 7 compared with those in other groups. Pathological studies also showed a faster and better healing effect and less inflammatory response in the BC groups than those in other groups. These results indicate high clinical potential of the BC biosynthesized by our improved method.
  • Article
    Abstract The selection, synthesis, modification and shaping of biomaterials are complex tasks within the biomedical field. Human and plant tissues, such as, wood, bone and cartilage are structured at the nanometer level and exhibit a hierarchical structure up to the macroscale. Their morphological similarities enable the exploitation of lignocellulosic materials in the development of nanostructured composites targeting tissue engineering and regeneration. In this review, lignocellulosic materials and their chemical constituents are highlighted as promising alternatives for the development of drug-delivery vehicles and for the engineering or regeneration of bone and cartilage. Special focus is given to the recent developments of lignocellulosic bionanocomposite supports that induce cell attachment and proliferation. Chemical modifications techniques as well as composite processing methodologies that enhance the biomaterial performance are reviewed. It is anticipated the increasing interest in nanocellulose, bacterial cellulose, hemicellulose and lignin from natural resources as added-value biomedical materials in the near future.
  • Article
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    Despite being the world's most abundant natural polymer and one of the most studied, cellulose is still challenging researchers. Cellulose is known to be insoluble in water and in many organic solvents, but can be dissolved in a number of solvents of intermediate properties, like N-methylmorpholine N-oxide and ionic liquids which, apparently, are not related. It can also be dissolved in water at extreme pHs, in particular if a cosolute of intermediate polarity is added. The insolubility in water is often referred to strong intermolecular hydrogen bonding between cellulose molecules. Revisiting some fundamental polymer physicochemical aspects (i.e. intermolecular interactions) a different picture is now revealed: cellulose is significantly amphiphilic and hydrophobic interactions are important to understand its solubility pattern. In this paper we try to provide a basis for developing novel solvents for cellulose based on a critical analysis of the intermolecular interactions involved and mechanisms of dissolution.