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Structure of sodium alginate after geometry optimization. Color code: red, O; white, H; gray, C; purple, Na.
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In the present research, molecular modeling methods were used to study novel porous soy protein conjugates with gelatin or alginate, which were recently developed as potential scaffolds for tissue engineering applications. Gelatin (protein) and alginate (polysaccharides) were chemically crosslinked to soy protein isolates (SPI) in order to obtain a...
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... was built as a block copolymer containing 12 sugar units: 6 units of α-L-guluronate (G) and 6 units of β-Dmannuronate (M) with a molecular mass of 2107 Da (Fig. 3). According to the literature, [7] the pKa of alginic acid is 1.5-3.5. Therefore, at pH 5.5-6.0 in which the crosslinking reaction is performed, the concentration of the ionized carboxylate groups is at least 100 times larger than the concentration of free carboxylic acid groups. Because the chain of the alginate includes only 12 sugar ...
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... As one of the most important carbohydrates, starch has been the object of extensive research. However, due to its large molecular size, simulations with starch are complicated and often require working with small portions and representative regions, whereas proteins get evaluated as small peptides and individual amino acids, while still obtaining satisfactory results (Bhopatkar et al., 2015;Cheng et al., 2018;Sakajiri et al., 2006;Knani et al., 2017). ...
Insects such as the black soldier fly (BSF) are recently being studied as food sources to address concerns about
how to meet the food demand of the growing world population, as conventional production lines for meat
proteins are currently unsustainable sources. Studies have been conducted evaluating the use of insect proteins to
produce extruded foods such as expanded snacks and meat analogues. However, this field of study is still quite
new and not much has been studied beyond digestibility and growth performance. The purpose of this work was
to evaluate the compatibility of protein extracted from BSF flour with corn flour starch within an extruded
balanced shrimp feed model through molecular dynamics simulations, for which cohesive energy density and
solubility parameter (δ) of both components were determined. The calculations’ results for the protein molecule
systems yielded an average δ of 14.961 MPa0.5, while the δ for starch was calculated to be 23.166 MPa0.5. The
range of difference between both δ (10 > δ > 7) suggests that the interaction of the BSF protein with corn starch
is of a semi-miscible nature. These results suggest that it is possible to obtain a stable starch-protein mixture
through the extrusion process
... This high stability of RC is due to the hydrogen bond between benzaldehyde and alginate structure, as confirmed by NCI analysis (Figure S11 in SI). This hydrogen bond is located between the carbonyl group of aldehyde and the hydroxyl groups on the surface of alginate, which can facilitate the activation of nucleophile attacks on the carbon atom of the aldehyde function [49][50][51][52]. The reaction between the RC and cyanocinnamonitrile conducts the formation of an intermediate complex (IC1). ...
The naturally occurring sodium alginate (SA) biopolymer from the Sargassum muticum (Yendo) Fensholt was employed as a green organocatalyst for the synthesis of 4H-pyran derivatives. The naturally extracted macromolecule was fully characterized using different analyses, including nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and Energy Dispersive X-ray Analysis (EDX). The catalytic activity of SA was investigated in the one-pot reaction between aldehydes, malononitrile, and 1,3-dicarbonyl compounds in water at room temperature, and the corresponding 2-amino-3-cyano-4H-pyran derivatives were obtained with good to excellent yields. This organocatalyst was easily separated from the reaction mixture and reused for at least two consecutive cycles without a significant loss of its catalytic activity or selectivity. From the mechanistic point of view, density functional theory (DFT) and NCI analyses were performed for the first time to explain the regioselectivity outcomes for the synthesis of 2-amino-3-cyano-4H-pyran derivatives using SA as a green organocatalyst.
... Molecular dynamics is a well-established method for investigating and screening polymers and polymer blend systems as indicated in numerous works [72][73][74][75][76][77]. There are, however, only a few works concerning molecular simulations of gelatin [57,78,79]. One possible reason for this is that gelatin is a difficult system to model since it is composed of over 10 amino acids in a pseudo-random order. ...
The presented research is focused on an investigation of the effect of the addition of polyvinyl alcohol (PVA) to a gelatin-based hydrogel on the functional properties of the resulting material. The main purpose was to experimentally determine and compare the properties of hydrogels differing from the content of PVA in the blend. Subsequently, the utility of these matrices for the production of an immobilized invertase preparation with improved operational stability was examined. We also propose a useful computational tool to predict the properties of the final material depending on the proportions of both components in order to design the feature range of the hydrogel blend desired for a strictly specified immobilization system (of enzyme/carrier type). Based on experimental research, it was found that an increase in the PVA content in gelatin hydrogels contributes to obtaining materials with a visibly higher packaging density, degree of swelling, and water absorption capacity. In the case of hydrolytic degradation and compressive strength, the opposite tendency was observed. The functionality studies of gelatin and gelatin/PVA hydrogels for enzyme immobilization indicate the very promising potential of invertase entrapped in a gelatin/PVA hydrogel matrix as a stable biocatalyst for industrial use. The molecular modeling analysis performed in this work provides qualitative information about the tendencies of the macroscopic parameters observed with the increase in the PVA and insight into the chemical nature of these dependencies.
... 35−38 However, it is worth to note that limited studies are found that examine protein− ligand docking with soy protein and zein. 39,40 To the best of our knowledge, the protein−ligand docking approach has not been used previously as a tool to predict the properties and performance of bioplastic films, and this study is a first work that applied this approach toward these materials. ...
... That makes it the material of choice in many targeted applications in the food, cosmetics, pharmaceutical and medical industries [40][41][42][43]. Although there are numerous experimental studies concerning the properties and utilization of gelatin, papers analysing its features using molecular modeling are few at most [44][45][46][47]. One probable reason is the difficulty in creating a reliable atomistic model due to the complex nature of gelatin as a biopolymer. ...
To successfully design and optimize the application of hydrogel matrices one has to effectively combine computational design tools with experimental methods. In this context, one of the most promising techniques is molecular modeling, which requires however accurate molecular models representing the investigated material. Although this method has been successfully used over the years for predicting the properties of polymers, its application to biopolymers, including gelatin, is limited. In this paper we provide a method for creating an atomistic representation of gelatin based on the modified FASTA codes of natural collagen. We show that the model created in this manner reproduces known experimental values of gelatin properties like density, glass-rubber transition temperature, WAXS profile and isobaric thermal expansion coefficient. We also present that molecular dynamics using the INTERFACE force field provides enough accuracy to track changes of density, fractional free volume and Hansen solubility coefficient over a narrow temperature regime (273–318 K) with 1 K accuracy. Thus we depict that using molecular dynamics one can predict properties of gelatin biopolymer as an efficient matrix for immobilization of various bioactive compounds, including enzymes.
... 5 In previous work, we have used molecular modeling methods to study novel porous soy protein conjugates with gelatin or alginate, which were recently developed as potential scaffolds for tissue engineering applications. 6 The aim of the present research is to study gelatin and alginate conjugates with three antibiotic drugs using molecular dynamics simulation.Gelatin is a mixture of polypeptides obtained by partial hydrolysis of collagen extracted from connective tissues of animals, primarily from bovine and porcine skin and bones. 7,8 Gelatin "type A" from porcine skin was used in the experimental study. ...
... Alginate and gelatin molecules were built as described in previous paper. 6 Alginate was built as a block copolymer containing 12 sugar units: 6 units of α-L-guluronate (G) and 6 units of β-D-mannuronate (M). Of the 12 carboxylic groups, one was free, and 11 were ionized. ...
In the present research, molecular modeling methods were used to study a novel bioadhesive composed of gelatin (protein) and alginate (polysaccharides), crosslinked with N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride (EDC) and N‐hydroxysuccinimide (NHS). Three antibiotic drugs were added to the bioadhesive: Vancomycin, Ofloxacin, and Clindamycin. Computational tools were applied to estimate the crosslinking degree and compare the effect of the antibiotics on the physical properties of the gelatin‐alginate conjugate. The crosslinking degree was estimated by calculating the enthalpy of mixing of gelatin with alginate and their interaction with the crosslinking agents. The calculations revealed that gelatin mixes well with alginate, which enables their crosslinking. Various ratios between EDC and NHS were examined, and an optimal ratio was found. The interaction of alginate‐gelatin conjugate with the antibiotics was correlated to the experimental results of bonding strength. The most significant interaction of the conjugate is with clindamycin. The gelatin part is responsible for the strong interaction with clindamycin, and alginate forms strong interaction with ofloxacin. Thus, the interaction of alginate‐gelatin conjugate with the antibiotics is governed by the proportion between gelatin and alginate in the conjugate. The degradation rate of gelatin‐alginate was related to its interaction with water. It was found that the conjugate is highly hydrophilic. Gelatin is more soluble in water than both alginate and alginate‐gelatin and is probably the part in the conjugate that governs the solubility and degradation rate. Therefore, the degradation rate of the conjugate can be controlled by changing the proportion between gelatin and alginate.
... RDF may serve as a tool to estimate intermolecular interactions. [51]. The height of the RDF frequency peak should exceed one, in order to have a significant interaction. ...
... The solubility parameters (δ) for PP, HNTs, carvacrol, and their combinations, were calculated using MD simulations and the results are summarized. In addition, we calculated the enthalpy of mixing values (ΔHmix) using Equation (3) [51], and obtained values are included in Table 3. The energy of mixing values of PP-HNTs and PP-HNTs-carvacrol are both negative and very similar, suggesting that the HNTs and carvacrol interact separately with PP, and they do not interact between themselves. ...
... The solubility parameters (δ) for PP, HNTs, carvacrol, and their combinations, were calculated using MD simulations and the results are summarized. In addition, we calculated the enthalpy of mixing values (∆H mix ) using Equation (3) [51], and obtained values are included in Table 3. The energy of mixing values of PP-HNTs and PP-HNTs-carvacrol are both negative and very similar, suggesting that the HNTs and carvacrol interact separately with PP, and they do not interact between themselves. ...
Significant research has been directed toward the incorporation of bioactive plant extracts or essential oils (EOs) into polymers to endow the latter with antimicrobial functionality. EOs offer a unique combination of having broad antimicrobial activity from a natural source, generally recognized as safe (GRAS) recognition in the US, and a volatile nature. However, their volatility also presents a major challenge in their incorporation into polymers by conventional high-temperature-processing techniques. Herein, antimicrobial polypropylene (PP) cast films were produced by incorporating carvacrol (a model EO) or carvacrol, loaded into halloysite nanotubes (HNTs), via melt compounding. We studied the composition-structure-property relationships in these systems, focusing on the effect of carvacrol on the composition of the films, the PP crystalline phase and its morphology and the films' mechanical and antimicrobial properties. For the first time, molecular dynamics simulations were applied to reveal the complex interactions between the components of these carvacrol-containing systems. We show that strong molecular interactions between PP and carvacrol minimize the loss of this highly-volatile EO during high-temperature polymer processing, enabling semi-industrial scale production. The resulting films exhibit outstanding antimicrobial properties against model microorganisms (Escherichia coli and Alternaria alternata). The PP/(HNTs-carvacrol) nanocomposite films, containing the carvacrol-loaded HNTs, display a higher level of crystalline order, superior mechanical properties and prolonged release of carvacrol, in comparison to PP/carvacrol blends. These properties are ascribed to the role of HNTs in these nanocomposites and their effect on the PP matrix and retained carvacrol content.
... RDF may serve as a tool to estimate intermolecular interactions. [51]. The height of the RDF frequency peak should exceed one, in order to have a significant interaction. ...
... The solubility parameters (δ) for PP, HNTs, carvacrol, and their combinations, were calculated using MD simulations and the results are summarized. In addition, we calculated the enthalpy of mixing values (ΔHmix) using Equation (3) [51], and obtained values are included in Table 3. The energy of mixing values of PP-HNTs and PP-HNTs-carvacrol are both negative and very similar, suggesting that the HNTs and carvacrol interact separately with PP, and they do not interact between themselves. ...
... The solubility parameters (δ) for PP, HNTs, carvacrol, and their combinations, were calculated using MD simulations and the results are summarized. In addition, we calculated the enthalpy of mixing values (∆H mix ) using Equation (3) [51], and obtained values are included in Table 3. The energy of mixing values of PP-HNTs and PP-HNTs-carvacrol are both negative and very similar, suggesting that the HNTs and carvacrol interact separately with PP, and they do not interact between themselves. ...
... Three different forms of soy protein exist depending on different concentrations (50% up to 90 %), namely soy flour, soy protein concentrate and soy protein isolate (SPI) [51]. Soy protein is composed of four fractions including 2S, 7S, 11S and 15S according to their sedimentation properties [52]. Two important subunits in soy protein are conglycinin 7S and glycinin 11S which include all amino acids and represent approximately 80% of the protein. ...
Biomaterials have been utilized in tissue engineering and regenerative medicine as synthetic or natural derived scaffolds to support cells in order to promote tissue regeneration and to restore the function of injured tissue. Different biomaterials chosen for scaffold fabrication may contain however some unfavorable properties. In order to bypass some of the limitations of synthetic polymers such as having undesirable degradation products and being inactive or, moreover, to tackle potential biocompatibility issues with animal derived proteins like immunogenicity, this project investigated soy protein isolate (SPI) as a green and abundant plant derived protein in a variety of structures for soft tissue engineering and wound dressing applications. Composite SPI films containing bioactive glasses (BG) showed hemostatic capability which is important for wound healing applications. Moreover, cell culture study results confirmed attachment, spreading and proliferation of mouse embryonic fibroblast (MEF) cells on these composite films, particularly for SPI films containing 13-93 BG that could be due to the smoother surface morphology of this film in comparison to other composite films fabricated with other BG composition. In order to suggest SPI based hydrogels for other types of wounds like diabetic ulcers or burn wounds, SPI was combined with alginate which is a well-known hydrogel that has been used for decades as wound dressing material. Alginate (Alg) has some drawbacks such as slow and uncontrolled degradation and poor cell adhesion properties which was solved in the present study by blending with SPI. Cytocompatibilty results of 2D cell culture on Alg/SPI hydrogels showed better cell attachment and proliferation for both human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblast (NHDF) cells compared to pure alginate hydrogel films. The addition of BG also promoted cell attachment and proliferation which might be due to changes in the surface morphology of the hydrogels and ionic dissolution products of BG. Nano indentation outcomes on Alg/SPI hydrogel films indicated higher effective Young’s modulus in comparison to pure Alg hydrogel films. As a 3D model, encapsulated human adipose-derived mesenchymal stem cells (hADSCs) in Alg/SPI hydrogel microcapsules indicated migration and proliferation of these cells compared to pure alginate microcapsules, which were found to be enhanced by increasing SPI content. Higher degradation profile of different compositions of Alg/SPI microcapsules compared to Alg microcapsules could be the reason for cell elongation and cell proliferation. In this research project two different techniques were considered to produce 3D SPI based scaffolds: electrospinning and bioplotting. The parameters for electrospinning SPI based fibrous scaffold were optimized and then scaffolds were characterized in terms of pore size, fiber diameter, porosity and mechanical properties. The effect of relative humidity on the fibers morphology was investigated. A preliminary cell biology study was carried out to assess the viability of MEF cells in contact with electrospun fibrous scaffolds. The results indicated no toxic effect compared to the control and these fibrous scaffolds were shown to support cell proliferation. Biofabrication of Alg/SPI hydrogels containing MEF cells was investigated to obtain 3D Alg/SPI constructs. Cell viability results were equivalent to the results obtained with capsules. Overall, the outcomes of these studies make the developed materials as promising candidates for applications in soft tissue engineering and wound healing applications and warrant further in vitro and in vivo investigations.
3D printing of high-strength natural polymer biodegradable hydrogel scaffolds simultaneously resembling the biomechanics of corneal tissue and facilitating tissue regeneration remains a huge challenge due to the inherent brittleness of natural polymer hydrogels and the demanding requirements of printing. Herein, concentrated aqueous solutions of gelatin and carbohydrazide modified alginate (Gel/Alg-CDH) are blended to form a natural polymer hydrogel ink, where the hydrazides in Alg-CDH are found to form strong hydrogen-bonds with the gelatin. The hydrogen-bonding-strengthened Gel/Alg-CDH hydrogel demonstrates an appropriate thickened viscosity and shear-thinning for extrusion printing. The strong hydrogen bonds contribute to remarkably increased mechanical properties of Gel/Alg-CDH hydrogel with a maximum elongation of over 400%. In addition, sequentially Ca2+-physical crosslinking and then moderately chemical crosslinking significantly enhance the mechanical properties of Gel/Alg-CDH hydrogels that ultimately exhibit an intriguing J-shaped stress-strain curve (tensile strength of 1.068 MPa and the toughness of 677.6 kJ/m2). The dually crosslinked Gel-Alg-CDH-Ca2+-EDC hydrogels demonstrate a high transparency, physiological swelling stability and rapid enzymatic degradability, as well as suturability. Growth factor and drug-loaded biomimetic bilayer hydrogel scaffold is customized via a multi-nozzle printing system. This bioactive bilayer hydrogel scaffold considerably promotes regeneration of corneal epithelium and stroma, and inhibits cornea scarring in rabbit cornea keratoplasty.
