Preparation and Characterization of Composite Blends Based on Polylactic Acid/Polycaprolactone and Silk.

Silk-reinforced polylactic acid/poly ε-caprolactone composites containing 1-7 wt % of silk fibers were fabricated through the melt-mixing method. The composites were then characterized by implementing Fourier transform infrared (FTIR), differential scanning calorimetry (DSC) and rheometry to investigate functional groups, thermal properties, rheological properties, and intrinsic viscosities of each composite. The crystallinity of the composites was found to decrease upon addition of silk, while, both storage modulus ( G') and loss modulus ( G″) were increased which is an indication of interface bonding between the polymer and silk. The composite containing 5% silk fiber (PLACLS5) showed the optimum results. The composites' morphological analysis was conducted by scanning electron micrograph coupled with energy dispersive X-ray (SEM-EDX) mapping to assess the fiber dispersion in the composite matrix. The contact angle measurements and in vitro degradation were performed to evaluate the hydrophilicity, free surface energy, and hydrolytic degradation of the composites. The results implied that addition of higher contents of silk fiber could reduce the degradation duration of the composites, which is due to the high hydrophilicity of the fiber, uniform fiber dispersion within the matrix, the porous structure, and consequently, the hydrophilic behavior of the composites. These composites can be great alternatives for both soft and hard tissue engineering applications.

Sustain release of dexamethasone from polyvinyl alcohol microparticle produced via coaxial microfluidic system.

OBJECTIVE: Polyvinyl alcohol (PVA) as a synthetic biopolymer has unique physicochemical properties to achieve an efficient drug carrier. In this study phenol-substituted polyvinyl alcohol (PVAPh) microparticle was made through a microfluidic system and peroxidase-mediated reaction in the presence of hydrogen peroxide and in following dexamethasone (Dex) release characteristics from this vehicle were elaborated for sustained drug delivery applications. RESULTS: PVAPh was synthesized by esterification and amidation reactions respectively. Then, the synthesized PVAPh solution containing peroxidase and Dex flowed within the inner channel of the coaxial microfluidic device while liquid paraffin saturated with H2O2 flowed from the outer channel. The monodisperse microparticles were produced in a spherical shape with an average diameter of 160 µm. The Dex was successfully encapsulated in PVAPh MP and its sustained release profile was maintained for up to 7 days. It was found that exposure of Dex-loaded PVAPh MPs to subcultured mouse embryonic fibroblast 10T1/2 cells had no deleterious effects on cell viability, morphology and growth rate. Moreover, the sustained release of Dex and the high mechanical durability of PVAPh MPs suggest an excellent prospect for the synthesized PVAPh and the developed method as a biocompatible carrier required for drug delivery and regenerative medicine.

Development and characterization of probiotic mucilage based edible films for the preservation of fruits and vegetables.

There is growing interest among the public and scientific community toward the use of probiotics to potentially restore the composition of the gut microbiome. With the aim of preparing eco-friendly probiotic edible films, we explored the addition of probiotics to the seed mucilage films of quince, flax, and basil. These mucilages are natural and compatible blends of different polysaccharides that have demonstrated medical benefits. All three seed mucilage films exhibited high moisture retention regardless of the presence of probiotics, which is needed to help preserve the moisture/freshness of food. Films from flax and quince mucilage were found to be more thermally stable and mechanically robust with higher elastic moduli and elongation at break than basil mucilage films. These films effectively protected fruits against UV light, maintaining the probiotics viability and inactivation rate during storage. Coated fruits and vegetables retained their freshness longer than uncoated produce, while quince-based probiotic films showed the best mechanical, physical, morphological and bacterial viability. This is the first report of the development, characterization and production of 100% natural mucilage-based probiotic edible coatings with enhanced barrier properties for food preservation applications containing probiotics.

Alginate sulfate-based hydrogel/nanofiber composite scaffold with controlled Kartogenin delivery for tissue engineering.

In this study, we fabricated two different arrangements of laminated composite scaffolds based on Alginate:Alginate sulfate hydrogel, PCL:Gelatin electrospun mat, and Kartogenin-PLGA nanoparticles (KGN-NPs). The optimized composite scaffold revealed a range of advantages such as improved mechanical features as well as less potential of damage (less dissipated energy), interconnected pores of hydrogel and fiber with adequate pore size, excellent swelling ratio, and controlled biodegradability. Furthermore, the synthesized KGN-NPs with spherical morphology were incorporated into the composite scaffold and exhibited a linear and sustained release of KGN within 30 days with desirable initial burst reduction (12% vs. 20%). Additionally, the cytotoxicity impact of the composite was evaluated. Resazurin assay and Live/Dead staining revealed that the optimized composite scaffold has no cytotoxic effect and could improve cell growth. Overall, according to the enhanced mechanical features, suitable environment for cellular growth, and sustained drug release, the optimized scaffold would be a good candidate for tissue regeneration.

A novel biocompatible polymeric blend for applications requiring high toughness and tailored degradation rate.

Finding the right balance in mechanical properties and degradation rate of biodegradable materials for biomedical applications is challenging, not only at the time of implantation but also during biodegradation. For instance, high elongation at break and toughness with a mid-term degradation rate are required for tendon scaffold or suture application, which cannot be found in each alpha polyester individually. Here, we hypothesise that blending semi-crystalline poly(p-dioxanone) (PDO) and poly(lactide-co-caprolactone) (LCL) in a specific composition will enhance the toughness while also enabling tailored degradation times. Hence, blends of PDO and LCL (PDO/LCL) were prepared in varying concentrations and formed into films by solvent casting. We thoroughly characterised the chemical, thermal, morphological, and mechanical properties of the new blends before and during hydrolytic degradation. Cellular performance was determined by seeding mouse fibroblasts onto the samples and culturing for 72 hours, before using proliferation assays and confocal imaging. We found that an increase in LCL content causes a decrease in hydrolytic degradation rate, as indicated by induced crystallinity, surface and bulk erosions, and tensile properties. Interestingly, the noncytotoxic blend containing 30% PDO and 70% LCL (PDO3LCL7) resulted in small PDO droplets uniformly dispersed within the LCL matrix and demonstrated a tailored degradation rate and toughening behaviour with a notable strain-hardening effect reaching 320% elongation at break; over 3 times the elongation of neat LCL. In summary, this work highlights the potential of PDO3LCL7 as a biomaterial for biomedical applications like tendon tissue engineering or high-performance absorbable sutures.

Developing multicomponent edible films based on chitosan, hybrid of essential oils, and nanofibers: Study on physicochemical and antibacterial properties.

Plastic waste is one of the major threats to the environment, and an urgent need to replace synthetic plastics with sustainable materials is progressively growing. Herein, sustainable films based on chitosan, Satureja, and Thyme essential oils (EOs), and chitosan nanofibers (NF) were developed for the first time. To this end, 1% (w/w) of EOs and 2 wt% of NF were incorporated into the chitosan solution. Despite the very similar chemical structure of carvacrol and thymol, which are the major constituents of Satureja and Thyme EOs, respectively, they imposed notably different effects on the physicochemical properties of chitosan films. Thyme EO was more efficient at establishing hydrogen bonds with chitosan. The disruptive effect of EOs on the crystalline network of chitosan was demonstrated through X-ray diffraction analysis. Satureja and Thyme EOs decreased and increased the barrier property of the chitosan films against water vapor, respectively. However, the barrier property was greatly improved in the presence of chitosan nanofibers. Satureja EO exhibited a more efficient antibacterial property against E. coli rather than Thyme EO. The fruits and vegetables, coated by the chitosan/EO/NF system, were less perished as compared with the control and chitosan-coated samples indicating the promising potential of the developed system to be used as edible and sustainable films and coatings due to their enhanced antibacterial and barrier properties.

Preparation and characterization of polylactic-co-glycolic acid/insulin nanoparticles encapsulated in methacrylate coated gelatin with sustained release for specific medical applications.

This study aimed to examine the possibility of using insulin orally with gelatin encapsulation to enhance the usefulness of the drug and increase the lifespan of insulin in the body using polylactic-co-glycolic acid (PLGA) nanoparticles alongside gelatin encapsulation. In this regard, PLGA was synthesized via ring opening polymerization, and PLGA/insulin nanoparticles were prepared by a modified emulsification-diffusion process. The resulting nanoparticles with various amounts of insulin were fully characterized using FTIR, DSC, DLS, zeta potential, SEM, and glucose uptake methods, with results indicating the interaction between the insulin and PLGA. The process efficiency of encapsulation was higher than 92%, while the encapsulation efficiency of nanoparticles, based on an insulin content of 20 to 40%, was optimized at 93%. According to the thermal studies, the PLGA encapsulation increases the thermal stability of the insulin. The morphological studies showed the fine dispersion of insulin in the PLGA matrix, which we further confirmed by the Kjeldahl method. According to the release studies and kinetics, in-vitro degradation, and particle size analysis, the sample loaded with 30% insulin showed optimum overall properties, and thus it was encapsulated with gelatin followed by coating with aqueous methacrylate coating. Release studies at pH values of 3 and 7.4, alongside the Kjeldahl method and standard dissolution test at pH 5.5, and glucose uptake assay tests clearly showed the capsules featured 3-4 h biodegradation resistance at a lower pH along with the sustained release, making these gelatin-encapsulated nanoparticles promising alternatives for oral applications.[Figure: see text].

Fabrication of chitosan/polyvinylpyrrolidone hydrogel scaffolds containing PLGA microparticles loaded with dexamethasone for biomedical applications.

One of the most effective approaches for treatment of chronic rhinosinusitis is the use of hydrogel scaffolds with the sustained release of a given required drug. With this in mind, first, we synthesized and characterized poly (lactide-co-glycolide) (PLGA) micro and nano particles loaded with dexamethasone (DEX). We observed a 7-day release of DEX from nanoparticles, while the microparticles showed a 22-day release profile. Due to their slower rate of release, the PLGA microparticles loaded with DEX (PLGADEX microparticles) were specifically chosen for this study. As a second step, chitosan/polyvinylpyrrolidone (PVP) based hydrogels were prepared in various weight ratios and the PLGADEX microparticles were optimized in their structure based on variable gelation times. The morphological studies showed PLGADEX microparticles homogenously dispersed in the hydrogels. Moreover, the effect of weight ratio in the presence and absence of optimum percentage of PLGADEX microparticles was studied. The resultant hydrogels demonstrated a range of advantages, including good mechanical strength, porous morphology, amorphous structure, high swelling ratio, controlled biodegradability rate, and antibacterial activity. Additionally, a cytotoxicity analysis confirmed that the hydrogel scaffolds do not have adverse effects on the cells; our release studies in the hydrogel with the highest PVP content also showed 80% release after 30 days. Based on these results we were able to predict and control some of the mechanical properties, including the microstructure of the scaffolds, as well as the drug release, by optimizing the polymers - microparticle concentration, plus their resulting interactions. This optimized hydrogel can become part of a suitable alternative for treatment of allergic rhinitis and chronic sinusitis.

Investigating the effect of tetracycline addition on nanocomposite hydrogels based on polyvinyl alcohol and chitosan nanoparticles for specific medical applications.

Hydrogels have been used in many biomedical applications such as drug delivery and tissue engineering in recent decades. To improve the physiochemical and antimicrobial properties of these hydrogels and developing their applications, hybrid systems consisting of hydrogels, biodegradable nanoparticles and antibiotics were synthesized. In this regard, nanocomposite hydrogels based on PVA, 5% chitosan nanoparticles (NC) and various contents of tetracycline were prepared using freezing-thawing cycles and characterized using Fourier transform infrared spectroscopy (FTIR), gel fraction, swelling, antibacterial and cell viability studies, contact angle measurements, scanning electron microscopy, hydrolytic degradation and release studies. The FTIR studies showed the interaction between PVA, NC and tetracycline, and upon addition of 5% tetracycline gel fraction increases. Antibacterial and cell viability studies showed great antibacterial activity against gram-negative and gram-positive bacteria and cell growth in the presence of tetracycline. NC and tetracycline well dispersed in the hydrogel matrix and upon addition of tetracycline hydrolytic degradation and hydrophilicity increased. Finally, according to the release studies, the hydrogels mechanism perfectly fitted in Peppas-Korsmeyer and Higuchi models. Therefore, according to the results, nanocomposite hydrogel containing 5% of tetracycline can be suggested as a good candidate for wound dressing and novel drug delivery systems such as colon-specific drugs.

Enhanced compatibility of starch with poly(lactic acid) and poly(ɛ-caprolactone) by incorporation of POSS nanoparticles: Study on thermal properties.

In this work, we explore the ability of polyhedral oligomeric silsesquioxane (POSS) nanoparticles to increase the compatibility of hydrophilic starch with hydrophobic poly(lactic acid) (PLA) and poly(ɛ-caprolactone) (PCL). Morphological analysis demonstrated that lower contents of POSS (0.5 and 1 wt%) enhances the compatibility of the system. However, higher inclusion of POSS results in the formation of aggregates and thus a lower level of compatibility. Transmission electron microscopy revealed that PCL acts as an intermediate between PLA and starch, and that POSS is primarily localized within the PLA and PCL phases. Based on differential scanning calorimetry, PLA's crystallinity increases from 22.9% to 31.6% upon adding a very low content of POSS (0.5 wt%). However, the PCL's crystallinity is slightly hampered due to formation of these PLA crystallites. In contrast with the crystallization behavior and based on the thermal degradation kinetics, we found the composite's thermal stability is greatly increased when moderate to high contents (3 and 5 wt%) of POSS are utilized. Dynamic mechanical analysis results also confirmed good POSS dispersion within the matrix, especially at lower contents. In conclusion, POSS serves as an efficient compatibilizer for PLA/starch/PCL systems with improved thermal properties.

Synthesis, physicochemical, rheological and in-vitro characterization of double-crosslinked hyaluronic acid hydrogels containing dexamethasone and PLGA/dexamethasone nanoparticles as hybrid systems for specific medical applications.

Injectable hydrogels and biodegradable nanoparticles are using in tissue engineering applications and drug delivery systems. To improve physiochemical properties of biomaterials and to develop their applications, hybrid systems consist of hydrogels, and biodegradable nanoparticles were synthesized. In this study, hybrid systems based on double crosslinked hyaluronic acid and PLGA/Dexamethasone sodium phosphate (PLGADEX) nanoparticles are designed and synthesized in several steps. At the first step, poly(l-lactide-co-glycolide) (PLGA) in a ratio of LLA:GA = 85:15 mol% was synthesized via ring-opening polymerization. Then, PLGADEX nanoparticles were synthesized in different ratios using the partially modified emulsification-diffusion method and fully characterized, and desirable nanoparticle was selected (PLGADEX20). At the second step, a double cross-linked hyaluronic acid (XHA) was prepared by mixing various ratios of amino-hyaluronic acid and aldehyde-hyaluronic acid in the presence of genipin. Finally, by mixing of various ratios of PLGADEX20 and Dexamethasone sodium phosphate (DEX) with different ratios of XHA, hybrid systems were prepared. Based on the characterization of hybrid samples and the release studies, hydrogels containing nanoparticles showed a controlled drug release, while the best sample with 3% of optimized nanoparticle was chosen. According to physiochemical and biological properties, these hybrid systems can be good candidates for anti-adhesion barriers, wound dressings, and novel drug delivery systems.

Injectable PNIPAM/Hyaluronic acid hydrogels containing multipurpose modified particles for cartilage tissue engineering: Synthesis, characterization, drug release and cell culture study.

Novel injectable thermosensitive PNIPAM/hyaluronic acid hydrogels containing various amounts of chitosan-g-acrylic acid coated PLGA (ACH-PLGA) micro/nanoparticles were synthesized and designed to facilitate the regeneration of cartilage tissue. The ACH-PLGA particles were used in the hydrogels to play a triple role: first, the allyl groups on the chitosan-g-acrylic acid shell act as crosslinkers for PNIPAM and improved the mechanical properties of the hydrogel to mimic the natural cartilage tissue. Second, PLGA core acts as a carrier for the controlled release of chondrogenic small molecule melatonin. Third, they could reduce the syneresis of the thermosensitive hydrogel during gelation. The optimum hydrogel with the minimum syneresis and the maximum compression modulus was chosen for further evaluations. This hydrogel showed a great integration with the natural cartilage during the adhesion test, and also, presented an interconnected porous structure in scanning electron microscopy images. Eventually, to evaluate the cytotoxicity, mesenchymal stem cells were encapsulated inside the hydrogel. MTT and Live/Dead assay showed that the hydrogel improved the cells growth and proliferation as compared to the tissue culture polystyrene. Histological study of glycosaminoglycan (GAG) showed that melatonin treatment has the ability to increase the GAG synthesis. Overall, due to the improved mechanical properties, low syneresis, the ability of sustained drug release and also high bioactivity, this injectable hydrogel is a promising material system for cartilage tissue engineering.

Optimization simulated injection molding process for ultrahigh molecular weight polyethylene nanocomposite hip liner using response surface methodology and simulation of mechanical behavior.

In this study, injection molding process of ultrahigh molecular weight polyethylene (UHMWPE) reinforced with nano-hydroxyapatite (nHA) was simulated and optimized through minimizing the shrinkage and warpage of the hip liners as an essential part of a hip prosthesis. Fractional factorial design (FFD) was applied to the design of the experiment, modeling, and optimizing the shrinkage and warpage of UHMWPE/nHA composite liners. The Analysis of variance (ANOVA) was applied to find the importance of operative parameters and their effects. In this experiment, seven input parameters were surveyed, including mold temperature (A), melt temperature (B), injection time (C), packing time (D), packing pressure (E), coolant temperature (F), and type of liner (G). Two models were capable of predicting warpage and volumetric shrinkage (%) in different conditions with R2 of 0.9949 and 0.9989, respectively. According to the models, the optimized values of warpage and volumetric shrinkage are 0.287222 mm and 13.6613%, respectively. Meanwhile, a finite element analysis (FE analysis) was also carried out to examine the stress distribution in liners under the force values of demanding and daily activities. The Von-Mises stress distribution showed that both of the liners can be applied to all activities with no failure. However, UHMWPE/nHA liner is more resistant to the highest loads than UHMWPE liner due to the effect of nHA in the nanocomposite. Finally, according to the results of injection molding simulations, optimization, structural analysis as well as the tensile strength and wear resistance, UHMWPE/nHA liner is recommended for the production of a hip prosthesis.

Simulation of mechanical behavior and optimization of simulated injection molding process for PLA based antibacterial composite and nanocomposite bone screws using central composite design.

In this study, injection molding of three poly lactic acid (PLA) based bone screws was simulated and optimized through minimizing the shrinkage and warpage of the bone screws. The optimization was carried out by investigating the process factors such as coolant temperature, mold temperature, melt temperature, packing time, injection time, and packing pressure. A response surface methodology (RSM), based on the central composite design (CCD), was used to determine the effects of the process factors on the PLA based bone screws. Upon applying the method of maximizing the desirability function, optimization of the factors gave the lowest warpage and shrinkage for nanocomposite PLA bone screw (PLA9). Moreover, PLA9 has the greatest desirability among the selected materials for bone screw injection molding. Meanwhile, a finite element analysis (FE analysis) was also performed to determine the force values and concentration points which cause yielding of the screws under certain conditions. The Von-Mises stress distribution showed that PLA9 screw is more resistant against the highest loads as compared to the other ones. Finally, according to the results of injection molding simulations, the design of experiments (DOE) and structural analysis, PLA9 screw is recommended as the best candidate for the production of biomedical materials among all the three types of screws.

Interface modified polylactic acid/starch/poly ε-caprolactone antibacterial nanocomposite blends for medical applications.

In this study, an optimized interface-modified ternary blend with antibacterial activity based on polylactic acid/starch/poly ε-caprolactone (PLASCL20), mixed with nano hydroxyapatite (nHA) via melt blending. This method results in a homogeneous nanocomposite blend in which the addition of 3% nHA improves the overall properties such as hydrolytic degradation, hydrophilicity, antibacterial activity and the drug release comparing to PLASCL20. Moreover, the simultaneous use of nHA and encapsulated triclosan (LATC30) compensated the negative effect of triclosan through increasing the possible cell attachment. According to the contact angle results, nHA was thermodynamically driven into the interface of PLA and PCL/Starch phases. The addition of 3% nHA showed a good adjustment between the hydrolytic degradation and the release profile, therefore, their electrospun microfibers demonstrated an improved fibroblast (L929) cell attachment. The aforementioned nanocomposite blend is a suitable antibacterial candidate for many medical applications with minimum side effects due to the controlled release of triclosan.

Investigating composite systems based on poly L-lactide and poly L-lactide/triclosan nanoparticles for tissue engineering and medical applications.

In this study, the encapsulated triclosan with a low molecular weight PLLA (LATC30) is dispersed into a PLLA having higher molecular weight via melt blending to increase the overall properties and particularly antibacterial activity of the system. The proposed method results in a completely homogenous composite as 5% LATC30 improved mechanical properties. For instance, the elongation at break was increased ca. 3%. The mechanical properties of the fabricated composites were also affected by the plasticizing role of LATC30. The kinetics of hydrolytic degradation in an accelerated condition was obtained using a novel method by the Beer-Lambert equation. It was found that the incorporation of LATC30 into the composite increases the rate of hydrolytic degradation. The calorimetry showed a reduction in crystallinity upon addition of LATC30. Moreover, the degradation of the composites was studied and fully described the kinetic analysis by the Flynn-Wall-Ozawa (FWO) method. From which, it was found that the activation energy of the system was decreased. As the LATC30 content of the composite was increased, the hydrophilicity of the composite was increased. The fabricated scaffolds with 5% LATC30 demonstrated a good osteoblast cell attachment and mineralization on the composite scaffolds. This composite is a suitable antibacterial candidate for the bone tissue engineering and medical applications since the real dosage of triclosan stays at ca. 1.5%.

Tuning cell adhesion on polymeric and nanocomposite surfaces: Role of topography versus superhydrophobicity.

Development of surface modification procedures which allow tuning the cell adhesion on the surface of biomaterials and devices is of great importance. In this study, the effects of different topographies and wettabilities on cell adhesion behavior of polymeric surfaces are investigated. To this end, an improved phase separation method was proposed to impart various wettabilities (hydrophobic and superhydrophobic) on polypropylene surfaces. Surface morphologies and compositions were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy, respectively. Cell culture was conducted to evaluate the adhesion of 4T1 mouse mammary tumor cells. It was found that processing conditions such as drying temperature is highly influential in cell adhesion behavior due to the formation of an utterly different surface topography. It was concluded that surface topography plays a more significant role in cell adhesion behavior rather than superhydrophobicity since the nano-scale topography highly inhibited the cell adhesion as compared to the micro-scale topography. Such cell repellent behavior could be very useful in many biomedical devices such as those in drug delivery and blood contacting applications as well as biosensors.