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Special Issue "Frontiers of Marine Biomaterials"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biomaterial Sciences".

Deadline for manuscript submissions: closed (31 July 2016)

Special Issue Editor

Guest Editor
Prof. Dr. Hermann Ehrlich

Institute of Experimental Physics, TU Bergakademie Freiberg, Germany
Website | E-Mail
Phone: +00493731 392867
Fax: +0049 3731 394314
Interests: marine biomaterials; biominerals; biocomposites and biomimetics

Special Issue Information

Dear Colleagues,

The principal motivation for this Special Issue is to use modern knowledge about the nano- and ultrastructural organization, as well as about the physico-chemical and materials properties of biological materials of marine origin. These include a broad variety of mineralized tissues, filaments, fibers, and nanostructured networks found in marine unicellular eukaryotes, such as diatoms, radiolarians, and dinoflagellates, and in multicellular invertebrates, such as sponges, corals, worms, molluscs, echinoderms, and arthropods. Additionally, biocomposites and biopolymers isolated from, and observed in, the diverse range of marine vertebrates (fishes, reptiles, birds, mammals) are of special interest. Once we understand the origin, nature, evolution, and structure–function relationship in materials that are made in marine living systems, we can then use these principles for biomimetic fabrication, design, and self-assembly of new hybride mineralized biopolymer composites for future biomedical and technical applications.

Prof. Dr. Hermann Ehrlich
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomaterials
  • chitin
  • biominerals
  • biocomposites
  • biomimetics

Published Papers (12 papers)

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Research

Jump to: Review

Open AccessArticle Validated HPAEC-PAD Method for the Determination of Fully Deacetylated Chitooligosaccharides
Int. J. Mol. Sci. 2016, 17(10), 1699; doi:10.3390/ijms17101699
Received: 28 July 2016 / Revised: 29 September 2016 / Accepted: 30 September 2016 / Published: 10 October 2016
Cited by 1 | PDF Full-text (914 KB) | HTML Full-text | XML Full-text
Abstract
An efficient and sensitive analytical method based on high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) was established for the simultaneous separation and determination of glucosamine (GlcN)1 and chitooligosaccharides (COS) ranging from (GlcN)2 to (GlcN)6 without prior derivatization. Detection
[...] Read more.
An efficient and sensitive analytical method based on high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) was established for the simultaneous separation and determination of glucosamine (GlcN)1 and chitooligosaccharides (COS) ranging from (GlcN)2 to (GlcN)6 without prior derivatization. Detection limits were 0.003 to 0.016 mg/L (corresponding to 0.4–0.6 pmol), and the linear range was 0.2 to 10 mg/L. The optimized analysis was carried out on a CarboPac-PA100 analytical column (4 × 250 mm) using isocratic elution with 0.2 M aqueous sodium hydroxide-water mixture (10:90, v/v) as the mobile phase at a 0.4 mL/min flow rate. Regression equations revealed a good linear relationship (R2 = 0.9979–0.9995, n = 7) within the test ranges. Quality parameters, including precision and accuracy, were fully validated and found to be satisfactory. The fully validated HPAEC-PAD method was readily applied for the quantification of (GlcN)1–6 in a commercial COS technical concentrate. The established method was also used to monitor the acid hydrolysis of a COS technical concentrate to ensure optimization of reaction conditions and minimization of (GlcN)1 degradation. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessArticle Diatom Valve Three-Dimensional Representation: A New Imaging Method Based on Combined Microscopies
Int. J. Mol. Sci. 2016, 17(10), 1645; doi:10.3390/ijms17101645
Received: 12 July 2016 / Revised: 30 August 2016 / Accepted: 23 September 2016 / Published: 28 September 2016
Cited by 2 | PDF Full-text (4119 KB) | HTML Full-text | XML Full-text
Abstract
The frustule of diatoms, unicellular microalgae, shows very interesting photonic features, generally related to its complicated and quasi-periodic micro- and nano-structure. In order to simulate light propagation inside and through this natural structure, it is important to develop three-dimensional (3D) models for synthetic
[...] Read more.
The frustule of diatoms, unicellular microalgae, shows very interesting photonic features, generally related to its complicated and quasi-periodic micro- and nano-structure. In order to simulate light propagation inside and through this natural structure, it is important to develop three-dimensional (3D) models for synthetic replica with high spatial resolution. In this paper, we present a new method that generates images of microscopic diatoms with high definition, by merging scanning electron microscopy and digital holography microscopy or atomic force microscopy data. Starting from two digital images, both acquired separately with standard characterization procedures, a high spatial resolution (Δz = λ/20, Δx = Δy ≅ 100 nm, at least) 3D model of the object has been generated. Then, the two sets of data have been processed by matrix formalism, using an original mathematical algorithm implemented on a commercially available software. The developed methodology could be also of broad interest in the design and fabrication of micro-opto-electro-mechanical systems. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessArticle Sodium Copper Chlorophyllin Immobilization onto Hippospongia communis Marine Demosponge Skeleton and Its Antibacterial Activity
Int. J. Mol. Sci. 2016, 17(10), 1564; doi:10.3390/ijms17101564
Received: 28 July 2016 / Revised: 5 September 2016 / Accepted: 9 September 2016 / Published: 27 September 2016
PDF Full-text (3120 KB) | HTML Full-text | XML Full-text
Abstract
In this study, Hippospongia communis marine demosponge skeleton was used as an adsorbent for sodium copper chlorophyllin (SCC). Obtained results indicate the high sorption capacity of this biomaterial with respect to SCC. Batch experiments were performed under different conditions and kinetic and isotherms
[...] Read more.
In this study, Hippospongia communis marine demosponge skeleton was used as an adsorbent for sodium copper chlorophyllin (SCC). Obtained results indicate the high sorption capacity of this biomaterial with respect to SCC. Batch experiments were performed under different conditions and kinetic and isotherms properties were investigated. Acidic pH and the addition of sodium chloride increased SCC adsorption. The experimental data were well described by a pseudo-second order kinetic model. Equilibrium adsorption isotherms were determined and the experimental data were analyzed using both Langmuir and Freundlich isotherms. The effectiveness of the process was confirmed by 13C Cross Polarization Magic Angle Spinning Nuclear Magnetic Resonance (13C CP/MAS NMR), Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS) and thermogravimetric analysis (TG). This novel SCC-sponge-based functional hybrid material was found to exhibit antimicrobial activity against the gram-positive bacterium Staphylococcus aureus. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessArticle Candida antarctica Lipase B Immobilized onto Chitin Conjugated with POSS® Compounds: Useful Tool for Rapeseed Oil Conversion
Int. J. Mol. Sci. 2016, 17(9), 1581; doi:10.3390/ijms17091581
Received: 28 July 2016 / Revised: 8 September 2016 / Accepted: 9 September 2016 / Published: 20 September 2016
Cited by 4 | PDF Full-text (2141 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new method is proposed for the production of a novel chitin-polyhedral oligomeric silsesquioxanes (POSS) enzyme support. Analysis by such techniques as X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy confirmed the effective functionalization of the chitin surface. The resulting hybrid carriers were used
[...] Read more.
A new method is proposed for the production of a novel chitin-polyhedral oligomeric silsesquioxanes (POSS) enzyme support. Analysis by such techniques as X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy confirmed the effective functionalization of the chitin surface. The resulting hybrid carriers were used in the process of immobilization of the lipase type b from Candida antarctica (CALB). Fourier transform infrared spectroscopy (FTIR) confirmed the effective immobilization of the enzyme. The tests of the catalytic activity showed that the resulting support-biocatalyst systems remain hydrolytically active (retention of the hydrolytic activity up to 87% for the chitin + Methacryl POSS® cage mixture (MPOSS) + CALB after 24 h of the immobilization), as well as represents good thermal and operational stability, and retain over 80% of its activity in a wide range of temperatures (30–60 °C) and pH (6–9). Chitin-POSS-lipase systems were used in the transesterification processes of rapeseed oil at various reaction conditions. Produced systems allowed the total conversion of the oil to fatty acid methyl esters (FAME) and glycerol after 24 h of the process at pH 10 and a temperature 40 °C, while the Methacryl POSS® cage mixture (MPOSS) was used as a chitin-modifying agent. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessArticle Alginate and Algal-Based Beads for the Sorption of Metal Cations: Cu(II) and Pb(II)
Int. J. Mol. Sci. 2016, 17(9), 1453; doi:10.3390/ijms17091453
Received: 29 July 2016 / Revised: 18 August 2016 / Accepted: 23 August 2016 / Published: 1 September 2016
Cited by 6 | PDF Full-text (6878 KB) | HTML Full-text | XML Full-text
Abstract
Alginate and algal-biomass (Laminaria digitata) beads were prepared by homogeneous Ca ionotropic gelation. In addition, glutaraldehyde-crosslinked poly (ethyleneimine) (PEI) was incorporated into algal beads. The three sorbents were characterized by scanning electron microscopy (SEM) coupled with energy dispersive X-ray analysis (EDX):
[...] Read more.
Alginate and algal-biomass (Laminaria digitata) beads were prepared by homogeneous Ca ionotropic gelation. In addition, glutaraldehyde-crosslinked poly (ethyleneimine) (PEI) was incorporated into algal beads. The three sorbents were characterized by scanning electron microscopy (SEM) coupled with energy dispersive X-ray analysis (EDX): the sorption occurs in the whole mass of the sorbents. Sorption experiments were conducted to evaluate the impact of pH, sorption isotherms, and uptake kinetics. A special attention was paid to the effect of drying (air-drying vs. freeze-drying) on the mass transfer properties. For alginate, freeze drying is required for maintaining the porosity of the hydrogel, while for algal-based sorbents the swelling of the material minimizes the impact of the drying procedure. The maximum sorption capacities observed from experiments were 415, 296 and 218 mg Pb g−1 and 112, 77 and 67 mg Cu g−1 for alginate, algal and algal/PEI beads respectively. Though the sorption capacities of algal-beads decreased slightly (compared to alginate beads), the greener and cheaper one-pot synthesis of algal beads makes this sorbent more competitive for environmental applications. PEI in algal beads decreases the sorption properties in the case of the sorption of metal cations under selected experimental conditions. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessArticle A New Route of Fucoidan Immobilization on Low Density Polyethylene and Its Blood Compatibility and Anticoagulation Activity
Int. J. Mol. Sci. 2016, 17(6), 908; doi:10.3390/ijms17060908
Received: 26 April 2016 / Revised: 3 June 2016 / Accepted: 6 June 2016 / Published: 9 June 2016
Cited by 2 | PDF Full-text (2347 KB) | HTML Full-text | XML Full-text
Abstract
Beside biomaterials’ bulk properties, their surface properties are equally important to control interfacial biocompatibility. However, due to the inadequate interaction with tissue, they may cause foreign body reaction. Moreover, surface induced thrombosis can occur when biomaterials are used for blood containing applications. Surface
[...] Read more.
Beside biomaterials’ bulk properties, their surface properties are equally important to control interfacial biocompatibility. However, due to the inadequate interaction with tissue, they may cause foreign body reaction. Moreover, surface induced thrombosis can occur when biomaterials are used for blood containing applications. Surface modification of the biomaterials can bring enhanced surface properties in biomedical applications. Sulfated polysaccharide coatings can be used to avoid surface induced thrombosis which may cause vascular occlusion (blocking the blood flow by blood clot), which results in serious health problems. Naturally occurring heparin is one of the sulfated polysaccharides most commonly used as an anticoagulant, but its long term usage causes hemorrhage. Marine sourced sulfated polysaccharide fucoidan is an alternative anticoagulant without the hemorrhage drawback. Heparin and fucoidan immobilization onto a low density polyethylene surface after functionalization by plasma has been studied. Surface energy was demonstrated by water contact angle test and chemical characterizations were carried out by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Surface morphology was monitored by scanning electron microscope and atomic force microscope. Finally, their anticoagulation activity was examined for prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT). Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessArticle Effect of Acetyl Group on Mechanical Properties of Chitin/Chitosan Nanocrystal: A Molecular Dynamics Study
Int. J. Mol. Sci. 2016, 17(1), 61; doi:10.3390/ijms17010061
Received: 12 December 2015 / Revised: 28 December 2015 / Accepted: 29 December 2015 / Published: 5 January 2016
Cited by 5 | PDF Full-text (5318 KB) | HTML Full-text | XML Full-text
Abstract
Chitin fiber is the load-bearing component in natural chitin-based materials. In these materials, chitin is always partially deacetylated to different levels, leading to diverse material properties. In order to understand how the acetyl group enhances the fracture resistance capability of chitin fiber, we
[...] Read more.
Chitin fiber is the load-bearing component in natural chitin-based materials. In these materials, chitin is always partially deacetylated to different levels, leading to diverse material properties. In order to understand how the acetyl group enhances the fracture resistance capability of chitin fiber, we constructed atomistic models of chitin with varied acetylation degree and analyzed the hydrogen bonding pattern, fracture, and stress-strain behavior of these models. We notice that the acetyl group can contribute to the formation of hydrogen bonds that can stabilize the crystalline structure. In addition, it is found that the specimen with a higher acetylation degree presents a greater resistance against fracture. This study describes the role of the functional group, acetyl groups, in crystalline chitin. Such information could provide preliminary understanding of nanomaterials when similar functional groups are encountered. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Review

Jump to: Research

Open AccessReview Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue
Int. J. Mol. Sci. 2017, 18(5), 901; doi:10.3390/ijms18050901
Received: 10 January 2017 / Revised: 5 April 2017 / Accepted: 11 April 2017 / Published: 25 April 2017
PDF Full-text (5265 KB) | HTML Full-text | XML Full-text
Abstract
Scaffolds for tissue engineering application may be made from a collagenous extracellular matrix (ECM) of connective tissues because the ECM can mimic the functions of the target tissue. The primary sources of collagenous ECM material are calf skin and bone. However, these sources
[...] Read more.
Scaffolds for tissue engineering application may be made from a collagenous extracellular matrix (ECM) of connective tissues because the ECM can mimic the functions of the target tissue. The primary sources of collagenous ECM material are calf skin and bone. However, these sources are associated with the risk of having bovine spongiform encephalopathy or transmissible spongiform encephalopathy. Alternative sources for collagenous ECM materials may be derived from livestock, e.g., pigs, and from marine animals, e.g., sea urchins. Collagenous ECM of the sea urchin possesses structural features and mechanical properties that are similar to those of mammalian ones. However, even more intriguing is that some tissues such as the ligamentous catch apparatus can exhibit mutability, namely rapid reversible changes in the tissue mechanical properties. These tissues are known as mutable collagenous tissues (MCTs). The mutability of these tissues has been the subject of on-going investigations, covering the biochemistry, structural biology and mechanical properties of the collagenous components. Recent studies point to a nerve-control system for regulating the ECM macromolecules that are involved in the sliding action of collagen fibrils in the MCT. This review discusses the key attributes of the structure and function of the ECM of the sea urchin ligaments that are related to the fibril-fibril sliding action—the focus is on the respective components within the hierarchical architecture of the tissue. In this context, structure refers to size, shape and separation distance of the ECM components while function is associated with mechanical properties e.g., strength and stiffness. For simplicity, the components that address the different length scale from the largest to the smallest are as follows: collagen fibres, collagen fibrils, interfibrillar matrix and collagen molecules. Application of recent theories of stress transfer and fracture mechanisms in fibre reinforced composites to a wide variety of collagen reinforcing (non-mutable) connective tissue, has allowed us to draw general conclusions concerning the mechanical response of the MCT at specific mechanical states, namely the stiff and complaint states. The intent of this review is to provide the latest insights, as well as identify technical challenges and opportunities, that may be useful for developing methods for effective mechanical support when adapting decellularised connective tissues from the sea urchin for tissue engineering or for the design of a synthetic analogue. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessReview Applications of Alginate-Based Bioinks in 3D Bioprinting
Int. J. Mol. Sci. 2016, 17(12), 1976; doi:10.3390/ijms17121976
Received: 5 October 2016 / Revised: 18 November 2016 / Accepted: 21 November 2016 / Published: 25 November 2016
Cited by 8 | PDF Full-text (978 KB) | HTML Full-text | XML Full-text
Abstract
Three-dimensional (3D) bioprinting is on the cusp of permitting the direct fabrication of artificial living tissue. Multicellular building blocks (bioinks) are dispensed layer by layer and scaled for the target construct. However, only a few materials are able to fulfill the considerable requirements
[...] Read more.
Three-dimensional (3D) bioprinting is on the cusp of permitting the direct fabrication of artificial living tissue. Multicellular building blocks (bioinks) are dispensed layer by layer and scaled for the target construct. However, only a few materials are able to fulfill the considerable requirements for suitable bioink formulation, a critical component of efficient 3D bioprinting. Alginate, a naturally occurring polysaccharide, is clearly the most commonly employed material in current bioinks. Here, we discuss the benefits and disadvantages of the use of alginate in 3D bioprinting by summarizing the most recent studies that used alginate for printing vascular tissue, bone and cartilage. In addition, other breakthroughs in the use of alginate in bioprinting are discussed, including strategies to improve its structural and degradation characteristics. In this review, we organize the available literature in order to inspire and accelerate novel alginate-based bioink formulations with enhanced properties for future applications in basic research, drug screening and regenerative medicine. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessReview Investigation of Self-Assembly Processes for Chitosan-Based Coagulant-Flocculant Systems: A Mini-Review
Int. J. Mol. Sci. 2016, 17(10), 1662; doi:10.3390/ijms17101662
Received: 1 August 2016 / Revised: 7 September 2016 / Accepted: 23 September 2016 / Published: 30 September 2016
Cited by 3 | PDF Full-text (2308 KB) | HTML Full-text | XML Full-text
Abstract
The presence of contaminants in wastewater poses significant challenges to water treatment processes and environmental remediation. The use of coagulation-flocculation represents a facile and efficient way of removing charged particles from water. The formation of stable colloidal flocs is necessary for floc aggregation
[...] Read more.
The presence of contaminants in wastewater poses significant challenges to water treatment processes and environmental remediation. The use of coagulation-flocculation represents a facile and efficient way of removing charged particles from water. The formation of stable colloidal flocs is necessary for floc aggregation and, hence, their subsequent removal. Aggregation occurs when these flocs form extended networks through the self-assembly of polyelectrolytes, such as the amine-based polysaccharide (chitosan), which form polymer “bridges” in a floc network. The aim of this overview is to evaluate how the self-assembly process of chitosan and its derivatives is influenced by factors related to the morphology of chitosan (flocculant) and the role of the solution conditions in the flocculation properties of chitosan and its modified forms. Chitosan has been used alone or in conjunction with a salt, such as aluminum sulphate, as an aid for the removal of various waterborne contaminants. Modified chitosan relates to grafted anionic or cationic groups onto the C-6 hydroxyl group or the amine group at C-2 on the glucosamine monomer of chitosan. By varying the parameters, such as molecular weight and the degree of deacetylation of chitosan, pH, reaction and settling time, dosage and temperature, self-assembly can be further investigated. This mini-review places an emphasis on the molecular-level details of the flocculation and the self-assembly processes for the marine-based biopolymer, chitosan. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessReview Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses
Int. J. Mol. Sci. 2016, 17(9), 1440; doi:10.3390/ijms17091440
Received: 1 July 2016 / Revised: 9 August 2016 / Accepted: 19 August 2016 / Published: 31 August 2016
Cited by 10 | PDF Full-text (4241 KB) | HTML Full-text | XML Full-text
Abstract
Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum
[...] Read more.
Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessReview Chitosan Effects on Plant Systems
Int. J. Mol. Sci. 2016, 17(7), 996; doi:10.3390/ijms17070996
Received: 4 May 2016 / Revised: 1 June 2016 / Accepted: 20 June 2016 / Published: 23 June 2016
Cited by 4 | PDF Full-text (245 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan (CHT) is a natural, safe, and cheap product of chitin deacetylation, widely used by several industries because of its interesting features. The availability of industrial quantities of CHT in the late 1980s enabled it to be tested in agriculture. CHT has been
[...] Read more.
Chitosan (CHT) is a natural, safe, and cheap product of chitin deacetylation, widely used by several industries because of its interesting features. The availability of industrial quantities of CHT in the late 1980s enabled it to be tested in agriculture. CHT has been proven to stimulate plant growth, to protect the safety of edible products, and to induce abiotic and biotic stress tolerance in various horticultural commodities. The stimulating effect of different enzyme activities to detoxify reactive oxygen species suggests the involvement of hydrogen peroxide and nitric oxide in CHT signaling. CHT could also interact with chromatin and directly affect gene expression. Recent innovative uses of CHT include synthesis of CHT nanoparticles as a valuable delivery system for fertilizers, herbicides, pesticides, and micronutrients for crop growth promotion by a balanced and sustained nutrition. In addition, CHT nanoparticles can safely deliver genetic material for plant transformation. This review presents an overview on the status of the use of CHT in plant systems. Attention was given to the research that suggested the use of CHT for sustainable crop productivity. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Induction of premature senescence by the microtubule-stabilizing agents peloruside A. discodermolide, and paclitaxel.
Authors: Ariane Chan, Ian Paterson, John H. Miller
Abstract: Induction of premature senescence can be an effective anti-tumour action, similar to mitotic block and induction of apoptosis. Little information is available on induction of senescence by microtubule-targeting drugs. In the present study, the induction of senescence in cell cultures by the microtubule-stabilizing agents peloruside A, paclitaxel, and discodermolide, and, as a positive control, the DNA-damaging agent doxorubicin, was investigated using a b-galactosidase (SA-b-gal) assay to assess the presence of a senescence phenotype, a 5-ethynyl-2'-deoxyuridine (EdU)) incorporation assay coupled to flow cytometry to determine if DNA synthesis was inhibited, and a clonogenic assay to assess whether senescent cells were proliferating or not. Since senescence often leads to activation of the p53 and pRb tumour suppressor pathways, Western blotting was also carried out to determine if these two proteins were upregulated during the induction of premature senescence. The concentrations of all four drugs that were able to increased SA-β-gal activity also significantly showed a reduction in clonogenic survival. As expected, doxorubicin was the most effective at inducing a senescent phenotype, followed in order of potency by discodermolide, paclitaxel, then peloruside. A peak in p53 was seen followed by a subsequent decrease back to control levels following treatment with three of the four compounds, including peloruside A and discodermolide, but not paclitaxel. A significant decrease in pRb in response to all four drugs suggested that, like p53 and p21, pRb was not involved in maintaining the senescent phenotype. With regard to the senescent action of peloruside A, it was concluded that at low concentrations, premature senescence played an important, but not predominant, role in its mode of action.

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