Fabrication and characterization of transparent nanocomposite films based on poly (lactic acid)/polyethylene glycol reinforced with nano glass flake.

Developing new biodegradable packaging with superior properties and advanced functionalities is one of the most emerging research areas of interest in food packaging. In this study, PLA/PEG-based nanocomposite films incorporated with different amounts of nano glass flake (NGF) (0, 0.5, 1, and 2 phr) were fabricated via casting solution for applications in food packaging. The ATR-FTIR displayed no chemical interaction between the PLA/PEG-based matrix and NGF particles. The scanning electron microscopy (SEM) observations exhibited a relatively smooth and homogeneous surface without defects. Incorporation of the NGF into the PLA/PEG-based matrix did not affect the color and opacity of the fabricated films. The prepared nanocomposite films were highly transparent and exhibited superior properties such as increased hydrophobicity, appreciable oxygen barrier properties, and enhanced thermal stability. Dynamic mechanical thermal analysis (DMTA) and differential scanning calorimetry (DSC) analysis confirmed the existence of a single glass-transition temperature (Tg) as evidence of miscibility. According to the research results, the PLA/PEG/NGF1 nanocomposite film significantly offered the best overall performance. This work has developed new insight into the potential application of nano glass flakes in food packaging.

Polysaccharide-based (kappa carrageenan/carboxymethyl chitosan) nanofibrous membrane loaded with antifibrinolytic drug for rapid hemostasis- in vitro and in vivo evaluation.

This work aimed to establish a novel membrane consisting of hemostatic polysaccharides, kappa-carrageenan (KC), and carboxymethyl chitosan (CMC) in tandem with polyvinyl alcohol that spun together as a matrix and loaded with tranexamic acid (TXA) as antifibrinolytic agent for further coagulation effect during and after oral surgeries. The electrospinning of KC was done for the first time and in comparison of CMC has better hemostatic efficacy. The effect of the hemostat was investigated by its surface morphology (SEM), FTIR/ATR analysis, swelling behavior in both PBS and blood, hydrophilicity, porosity, mechanical properties, and cumulative release rate. The effect of materials and the drug concentration ratio were considered. The effect of acetic acid percent in aqueous solutions of CMC/PVA and KC/PVA on morphology was investigated. The cell culture assay showed that all membranes interacted well (98 %) with fibroblast cells attached and grown on the fabricated substrate. Furthermore, the membranes are evaluated by clotting time, whole blood clotting, hemocompatibility, and platelet and RBC adhesion tests. Also, the hemostatic performance of the membrane was analyzed in vivo, using the tail and liver bleeding model in rats. Therefore, TXA loading into CMC and KC dressing could be an attractive hemostatic system for various clinical applications.

Polysaccharide-based polyampholyte complex formation: Investigating the role of intra-chain interactions.

The difference in inter-chain and intra-chain electrostatic attraction was investigated in polyelectrolyte and polyampholyte electrostatic complex formation. Three polymers with similar backbone molecular structures including chitosan (Ch) polycation, carboxymethyl cellulose (CMCe) polyanion, and carboxymethyl chitosan (CMCh) polyampholyte were used for this purpose. The turbidimetric, water content, and rheological measurements for polyampholyte self-complex showed more dependence on the ionic strength rather than the polyelectrolyte one. The degree of dissociation (α), dissociation constant (pKa), and intrinsic persistence length were calculated by applying the Katchalsky-Lifson model to potentiometric data. We studied the gyration radii as a function of Debye length and observed the polyampholyte chain contractions due to the intra-chain electrostatic attractions, which minimize the entropic gain of the inter-chain complex formation. This is in accordance with the decrease in pKa by αc for CMCh which is the opposite of that for the Ch and CMCe samples. We also found that the polyampholyte has less intrinsic and electrostatic persistence length compared with both polyanion and polycation with similar chain structures indicating the impact of the inter-chain electrostatic interaction on the complex properties. This study deepens our insight about the behavior of CMCh and the nature of difference between CMCh and Ch/CMCe electrostatic complexes.

Albumin-loaded thermo/pH dual-responsive nanogels based on sodium alginate and poly (N-vinyl caprolactam).

During the past decades, many researchers have tried to encapsulate medicines in biopolymer nanogels as injectable medicines. In the present study, dual-responsive bovine serum albumin (BSA)-loaded nanogels prepared from sodium alginate grafted poly (N-vinyl caprolactam) (PNVCL) have been reported. First, PNVCL-g-sodium alginate (PNVCL-g-Alg) was synthesized through free radical polymerization, and then nanogels were obtained from ionic crosslinking of sodium alginate in the presence of BSA. FTIR spectra showed that PNVCL-g-Alg nanogels were successfully prepared. Turbidimetry and rheometry analyses demonstrated the cloud point temperature near the human body. Particle size was evaluated using FE-SEM and dynamic light scattering and it was found that the size of particles in dry and swollen state are about 30 and 280 nm, respectively. The effect of temperature and pH on BSA release was evaluated. By comparing the drug release behavior, we found that the release of the protein at the temperature above the cloud point is faster than that at the temperature below the cloud point. The pH sensitivity of BSA-loaded PNVCL-g-Alg was evaluated at pH 5.5 and 7.4 and showed that the drug release was faster at acidic pH than at neutral pH.

Stimuli-responsive electrospun nanofibers based on PNVCL-PVAc copolymer in biomedical applications.

Poly(N-vinylcaprolactam) (PNVCL) is a suitable alternative for biomedical applications due to its biocompatibility, biodegradability, non-toxicity, and showing phase transition at the human body temperature range. The purpose of this study was to synthesize a high molecular weight PNVCL-PVAc thermo-responsive copolymer with broad mass distribution suitable for electrospun nanofiber fabrication. The chemical structure of the synthesized materials was detected by FTIR and 1HNMR spectroscopies. N-Vinyl caprolactam/vinyl acetate copolymers (159,680 molecular weight (g/mol) and 2.51 PDI) were synthesized by radical polymerization. The phase transition temperature of N-vinyl caprolactam/vinyl acetate copolymer was determined by conducting a contact angle test at various temperatures (25, 26, 28, and 30 [Formula: see text]). The biocompatibility of the nanofibers was also evaluated, and both qualitative and quantitative results showed that the growth and proliferation of 929L mouse fibroblast cells increased to 80% within 48 h. These results revealed that the synthesized nanofibers were biocompatible and not cytotoxic. The results confirmed that the synthesized copolymers have good characteristics for biomedical applications.

Magnetic dual-responsive semi-IPN nanogels based on chitosan/PNVCL and study on BSA release behavior.

Magnetic thermoresponsive nanogels present a promising new approach for targeted drug delivery. In the present study, bovine serum albumin (BSA) loaded thermo-responsive magnetic semi-IPN nanogels (MTRSI-NGs) were developed. At first poly(N-vinyl caprolactam) (PNVCL) was synthesized by free radical polymerization and then MTRSI-NGs were prepared by crosslinking chitosan in presence of chitosan and Fe3O4. The formation of MTRSI-NGs has been confirmed by FTIR, and the average molecular weight of PNVCL was determined by GPC analysis. Rheological and turbidimetry analysis were used to determine lower critical solution temperature (LCST) of PNVCL and magnetic thermo-responsive nanogels (MTRSI-NGs) around 32 and 37 °C, respectively. FE-SEM analysis showed particle size at less than 20 nm in the dried state. Dynamic light scattering determined particle size at about 30 nm in a swelling state. The analysis of release behavior showed that the BSA release ratio at 40 °C was faster than 25 °C. The pH release behavior was evaluated at pH 5.5 and 7.4 and showed that the drug release rate at pH 5.5 was more rapid than pH 7.4. The results show MTRSI-NGs are applicable to protein targeted delivery by thermosensitive targeted drug delivery systems.

Controlled curcumin release from nanofibers based on amphiphilic-block segmented polyurethanes.

A series of biodegradable amphiphilic-block segmented polyurethanes (SPUs) are designed and synthesized based on di-block and tri-block macrodiols of polycaprolactone (PCL) and polyethylene glycol (PEG). Curcumin, as a model herbal antibacterial agent, is used due to its effective inhibitory action against Gram-positive and Gram-negative bacteria. Curcumin-loaded nanofibers, with 400-900 nm diameter range, have been prepared by electrospinning of SPUs. The synthesized SPUs can be used for wound dressing applications due to their excellent mechanical properties and higher hydrophilicity in comparison to PCL-based polyurethane. The elongation-at-break of tri-block SPU with PEG-PCL-PEG soft segments is 350% when produced as an electrospun mat and that for film is 1500%. In vitro release of curcumin, examined by UV-Vis spectroscopy, shows a steady release during 18 days. The inclusion of PEG chains in the soft segment increases the hydrophilicity and biodegradation rate of the electrospun mats compared to a PCL-based polyurethane, which eventually results in a higher curcumin release rate. The antibacterial activity of 50 mg of 10% curcumin-loaded SPU nanofibers is about 100% and 93% against Escherichia coli (E. coli ATCC: 25922) and Staphylococcus aureus (S. aureus ATCC: 6538), respectively. Nontoxic behavior of the scaffolds is evaluated through MTT assay against L929 mouse fibroblast cells. The results show that the synthesized SPUs can be used as a nanoscale sustained release carrier. The SPU with PEG-PCL-PEG soft segments is an excellent candidate for wound dressing in tissues undergoing large deformations during normal activities.

Controlling alginate oxidation conditions for making alginate-gelatin hydrogels.

In the present work, we discuss how oxidation conditions can affect the physical properties of oxidized alginate and crosslinking it with gelatin. We show that the amount of aldehyde groups produced on oxidized alginate backbone increases by increasing alginate concentration even in constant molar ratio of sodium periodate to alginate's repeating units. Increasing the concentration of alginate solution, promote the extent of chain scission and decreases the molecular weight of oxidized alginate, which can be due to the increased possibility of molecular collisions and oxidizing two adjacent uronic acids in the chain. By changing the oxidation condition, therefore, we can produce oxidized alginate with same degree of oxidation but different molecular weights, which change the sol-gel state of alginate-gelatin mixtures. Using oxidized alginates with different molecular weights, we suggest that the aldehyde end groups in alginate chains have the dominant effect in crosslinking with gelatin.

Influences of modified bacterial cellulose nanofibers (BCNs) on structural, thermophysical, optical, and barrier properties of poly ethylene-co-vinyl acetate (EVA) nanocomposite.

The BCNs were chemically modified using acetic anhydride with the aim of improving its dispersion and interfacial adhesion. Acetylation of BCNs was confirmed by FT-IR spectroscopy. Morphology studies using TEM and SEM revealed that a reasonable dispersion of the modified BCNs in the EVA matrix was accomplished. The DSC data displayed a little shift in the Tg to higher temperatures with the incorporation of both modified and unmodified BCNs. Increased thermal stability of the nanocomposites consisting acetylated BCNs was confirmed by TGA technique. DMA measurements highlighted that the storage modulus increased and the damping properties decreased for the nanocomposites with regard to the neat EVA.

[PhSiO1.5]8,10,12 as nanoreactors for non-enzymatic introduction of ortho, meta or para-hydroxyl groups to aromatic molecules.

Traditional electrophilic bromination follows long established "rules": electron-withdrawing substituents cause bromination selective for meta positions, whereas electron-donating substituents favor ortho and para bromination. In contrast, in the [PhSiO1.5]8,10,12 silsesquioxanes, the cages act as bulky, electron withdrawing groups equivalent to CF3; yet bromination under mild conditions, without a catalyst, greatly favors ortho substitution. Surprisingly, ICl iodination without a catalyst favors (>90%) para substitution [p-IC6H4SiO1.5]8,10,12. Finally, nitration and Friedel-Crafts acylation and sulfonylation are highly meta selective, >80%. In principle, the two halogenation formats coupled with the traditional electrophilic reactions provide selective functionalization at each position on the aromatic ring. Furthermore, halogenation serves as a starting point for the synthesis of two structural isomers of practical utility, i.e. in drug prospecting. The o-bromo and p-iodo compounds are easily modified by catalytic cross-coupling to append diverse functional groups. Thereafter, F-/H2O2 treatment cleaves the Si-C bonds replacing Si with OH. This represents a rare opportunity to introduce hydroxyl groups to aromatic rings, a process not easily accomplished using traditional organic synthesis methods. The as-produced phenol provides additional opportunities for modification. Each cage can be considered a nanoreactor generating 8-12 product molecules. Examples given include syntheses of 4,2'-R,OH-stilbenes and 4,4'-R,OH-stilbenes (R = Me, CN). Unoptimized cleavage of the Br/I derivatives yields 55-85% phenol. Unoptimized cleavage of the stilbene derivatives yields 35-40% (3-5 equivalents of phenol) in the preliminary studies presented here. In contrast, meta R-phenol yields are 80% (7-10 mol per cage).

Substrate-mediated commitment of human embryonic stem cells for hepatic differentiation.

Human embryonic stem cell (hESC)-derived endodermal cells are of interest for the development of cellular therapies to treat disorders such as liver failure. The soluble form of activin A (Act) has been widely used as an in vitro inducer of definitive endoderm (DE). In this study, we have developed a nanofibrous poly (ɛ-caprolactone) substrate, biofunctionalized with Act, for directed differentiation of hESCs into DE. Bioconjugation of Act on nanofibrous meshes was confirmed by enzyme-linked immunosorbent assay (ELISA) and immunostaining. In order to investigate the bioactivity of immobilized Act (iAct), hESCs were cultivated on the Act-conjugated nanofibers for five days. The nanofibers with covalent iAct significantly increased expression levels of the endodermal markers SOX17, FOXA2, and CXCR4, compared with physically adsorbed Act (aAct) or without Act (noAct). In addition, iAct retained its bioactivity after storage for five days in the absence of cell seeding. The capability of cultivated cells to generate the DE-derived lineage was evaluated through further differentiation of seeded cells into hepatocyte-like cells (HLCs). Interestingly, the iAct sample showed a higher level of hepatic markers compared to the aAct sample. We also demonstrated that iAct in the presence of soluble Act (sAct) could improve the conventional protocol to generate HLCs from hESCs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2861-2872, 2016.

Nanotopographical control of human embryonic stem cell differentiation into definitive endoderm.

Derivation of definitive endoderm (DE) from human embryonic stem cells (hESCs) can address the needs of regenerative medicine for endoderm-derived organs such as the pancreas and liver. Fibrous substrates which topographically recapitulate native extracellular matrix have been known to promote the stem cell differentiation. However, the optimal fiber diameter remains to be determined for the desired differentiation. Here, we have developed a simple method to precisely fabricate electrospun poly(ε-caprolactone) fibers with four distinct average diameters at nano- and microscale levels (200, 500, 800, and 1300 nm). Human ESCs were cultured as clumps or single cells and induced into DE differentiation to determine the optimal topography leading to the promoted differentiation compared with planar culture plates. Gene expression analysis of the DE-induced cells showed significant upregulation of DE-specific genes exclusively on the 200-nm fibers. By Western blot analysis, significant expression of DE-specific proteins was found when hESCs were cultured on the 200 nm substrate as single cells rather than clumps, probably due to more efficient cell-matrix interaction realized by morphological observations of the cell colonies. The results indicated that nanofibrillar substrates, only at ultrathin fiber diameters, provided a better environment for DE differentiation of hESC, which holds great promise in prospective tissue engineering applications.