Improving Infection Resistance in Tissue Engineered Scaffolds for Tensile Applications Using Vancomycin-Embedded Melt Electrowritten Scaffolds

It is important to consider mechanical, biological, and antibacterial properties of scaffolds when used for tissue engineering applications. This study presents a method to create complex “wavy” architecture polycaprolactone (PCL) scaffolds toward the development of tissue engineered ligament and tendon tissue substitutes, fabricated using melt electrowriting (MEW) and loaded with vancomycin (5, 10, and 25% w/w). Scaffolds are characterized for both mechanical and biological properties. Loading PCL scaffolds with vancomycin with modified solvent evaporation technique achieves a high loading efficiency of maximum 18% w/w and high encapsulation efficiency with over 89%. Vancomycin loaded PCL scaffolds with all three doses (5, 10, and 25% w/w) display antibacterial activity against Gram-positive Staphylococcus aureus (S. aureus) up to 14 days of release. Initial burst followed by a sustained release is observed on all three vancomycin loaded scaffolds for up to 28 days. Importantly, in addition to antibacterial properties, vancomycin-loaded PCL scaffolds also display improved mechanical properties compared to traditional crosshatch design MEW scaffolds and are noncytotoxic at all concentrations as demonstrated by live-dead staining, cell attachment and proliferation assays indicating its potential as an effective treatment option for tissue regeneration in rotator cuff injuries or other tissues undergoing tensile biomechanical loading.     

Novel Organic Solvent Free Micro-/Nano-fibrillar,Nanoporous Scaffolds for Tissue Engineering

Novel organic solvent free micro-/nano-fibrillar composite scaffolds have been manufactured using poly(L-lactide) and glycol-modified poly(ethylene terephthalate) to evaluate cell growth potential on the nanoporous networks. The authors describe a method for producing nanoporous scaffolds from polymer blends and highlights some limitations and inaccuracies when measuring mechanical properties of fibrillar porous structures. It illustrates the importance of determining the actual cross-sectional surface area of the load resisting fibers rather than using the simple geometrical area if properties are to be determined accurately. Cellular-biocompatible testing with a mouse pre-osteoblastic (early bone-forming cells) cell line shows promise, with a live monolayer of cells present on the biomaterial after 7–10 days of culture. In addition, scaffolds have also been manufactured by using the traditional electrospinning method and their cyto-biocompatibility compared to the micro-/nano-fibrillar composite scaffolds, employing cell attachment and morphology studies. Some scaffold manufacturing issues have also been identified and discussed in relation to improved cell growth.     

Design,Fabrication, and Characterization of Novel Porous Conductive Scaffolds for Nerve Tissue Engineering

Highly conductive polypyrrole/graphene (PYG) nanocomposite was synthesized with chemical oxidation process via emulsion polymerization and used for the preparation of novel porous conductive gelatin/chitosan-based scaffolds. The effect of PYG loading on various properties of scaffolds was investigated. The obtained results indicated that by introducing PYG into the polymeric matrix, the porosity and swelling capacity decreased while electrical conductivity and Young's modulus demonstrated increasing trend. The in vitro biodegradation test revealed that pure gelatin/chitosan matrix lost 80% of its weight after six weeks in the presence of lysozyme whilst the biodegradation rate was significantly lower for the conductive scaffolds. Furthermore, Schwann cell attachment and proliferation were evaluated by MTT assay and SEM image and the results revealed significant cell biocompatibility of the conductive scaffold with low amount of PYG. The results confirmed the potential of gelatin/chitosan/PYG compounding as a suitable biomaterial for using in nerve tissue engineering applications in which electrical stimulation plays a vital role.     

Irbesartan‐loaded electrospun nanofibers‐based PVP K90 for the drug dissolution improvement: Fabrication,in vitro performance assessment,and in vivo evaluation

Irbesartan with a low bioavailability is known as a poorly water‐soluble drug. The purpose of this investigation is the improvement of physicochemical properties (such as solubility and dissolution rate) of Irbesartan using electrospun nanofibers‐based solid dispersion preparation. Nanofibers were prepared using certain weight ratios of the drug and polyvinylpyrrolidone K90 (PVP K90). Then, dissolution studies were carried out. Moreover, selected samples were examined by many different tests such as Fourier transform infra red (FTIR), differential scanning calorimetry (DSC), X‐ray diffraction (XRD), high‐performance liquid chromatography (HPLC), and scanning electron microscopy (SEM). Though solubility and dissolution rate of all Irbesartan‐PVP nanofibers improved, but the best result was obtained through of ENSD5 (3% (w/v) : 7% (w/v)). In sink condition approximately 97% of this sample was released during 60 min. The drug content was among the different batches from 40.55 ± 1.01 to 245.32 ± 1.77 μg/mL. The maximum saturation solubility was belonged to this sample. According to the results of the thermal analysis and FTIR spectroscopy, there is no chemical reaction between drug and carrier, also samples has not changed during the process. Amorphous structure for nanofibers was confirmed by DSC thermograms and XRD diffractograms and morphological structure of samples were observed by SEM images. Ultimately, in vivo studies were performed in healthy grey rabbits and the results were satisfactory. The drug–polymer nanofibers showed an increase in relative bioavailability than the plain Irbesartan suspension. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42212.     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Three Component Composite Scaffolds Based on PCL,Hydroxyapatite, and L-Lysine Obtained in TIPS-SL: Bioactive Material for Bone Tissue Engineering

In this research, we describe the properties of three-component composite foam scaffolds based on poly(ε-caprolactone) (PCL) as a matrix and hydroxyapatite whiskers (HAP) and L-Lysine as fillers (PCL/HAP/Lys with wt% ratio 50/48/2). The scaffolds were prepared using a thermally induced phase separation technique supported by salt leaching (TIPS-SL). All materials were precisely characterized: porosity, density, water uptake, wettability, DSC, and TGA measurements and compression tests were carried out. The microstructure of the obtained scaffolds was analyzed via SEM. It was found that the PCL/HAP/Lys scaffold has a 45% higher Young’s modulus and better wettability compared to the PCL/HAP system. At the same time, the porosity of the system was ~90%. The osteoblast hFOB 1.19 cell response was also investigated in osteogenic conditions (39 °C) and the cytokine release profile of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was determined. Modification of PCL scaffolds with HAP and L-Lysine significantly improved the proliferation of pre-osteoblasts cultured on such materials.     

Application of polymeric nanofibers in medical designs,part IV: Drug and biological materials delivery

Nanotechnology has potential applications in different sciences, especially in the biological sciences and medicine. The development of nanofibers has greatly enhanced the scope for fabricating designs that can potentially use in medical sciences. Nanofibers mimic the porous topography of natural extracellular matrix, and are advantageous for tissue regeneration and also sustained release of encapsulated drug or growth factor. In part IV the author summarizes the currently available applications of nanofibers in drug and biological materials delivery.     

Polyhydroxybutyrate (PHB) Scaffolds as a Model for Nerve Tissue Engineering Application: Fabrication and In Vitro Assay

In this study, we fabricated PHB scaffolds by solid/liquid phase separation method. The properties of fabricated scaffolds were investigated using SEM, DMTA, and DSC. Our studies noticed that for an approach to scaffolds that contain tubular morphology and better mechanical properties, the solution should be frozen near crystallization temperature. For in vitro evaluation, the P19 mouse embryonal cell line was used as a model system. Results notice that cells attach and differentiate to the nerve cell. In vitro assay shows that it is a suitable model for use as a platform for neural tissue engineering applications.     

Chitosan/OA nanoparticle as delivery system for celecoxib: Parameters affecting the particle size,encapsulation, and release

Self‐assembled nanoparticles prepared from amphiphilic chitosan/oleic acid (Ch/OA) have shown antibacterial activity and potential application as a carrier for hydrophobic anticancer drugs. In this study, a low molecular weight chitosan was modified with oleic acid obtaining a degree of substitution (DS) of 12%. The critical aggregation concentration (CAC) of the Ch/OA polymer obtained (0.025 mg mL^?1) is lower in comparison with some systems of chitosan‐fatty acids. The self‐assembled Ch/OA nanoparticle size was optimized by changing polymer concentration, solvent, method, and time of homogenization to obtain particles with sizes around 300 nm and positive zeta potential. The drug loading about 7 μg mL^?1 and encapsulation efficiency of 75.8 ± 3.6% for Celecoxib was affected by the drug concentration. In vitro release behavior performed in (PBS, pH 7.4) and MES buffer (pH 6) indicated a pH‐dependent drug release behavior. The self‐assembled systems show stability during 4 weeks after the encapsulation of the hydrophobic drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44472.     

Recent Advances in Artificially Sulfated Polysaccharides for Applications in Cell Growth and Differentiation,Drug Delivery,and Tissue Engineering

Artificially sulfated polysaccharides, as the mimetics of native heparin and heparan sulfate, are important bioactive compounds, since they show great potential for tuning crucial biological activities within living organisms. Herein, we summarize progress in the development of artificially sulfated polysaccharides, such as cellulose sulfate, chitosan sulfate, and other sulfated polysaccharides, with a particular focus on the fields of biomedical and bioengineering applications in the past ten years. Their effects on cell growth and differentiation, but also as building blocks for drug carriers and medical implants, are emphasized.     

Hydrophobically graded polyester polyol acrylate polymers: Synthesis,characterization, and microencapsulation of sulfamethoxazole for controlled release application

Polyester polyol macromers were prepared by using diacid‐diol condensation reaction using succinic acid as the acid component and polyethylene glycol 200 (PEG 200) as the diol component. Replacing PEG 200 with increasing amounts of butanediol resulted in macromers, which upon acrylation of end hydroxy groups and polymerization resulted in polymers with graded hydrophobicity depending on the amount of butanediol present in the polymer. These polymers showed expected trends in water equilibrium swells, equilibrium water contact angles, and in vitro degradation times depending on the amount of modification with butanediol. These polymers were used to microencapsulate sulfamethoxazole as a model drug and the in vitro delivery of the drug also followed the expected trend depending on the polymer hydrophobicity. Thus, it was shown that it is possible to prepare polyesters of graded properties by judicious selection of diacids and diols. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4058–4065, 2006     

Hollow,pH‐sensitive calcium–alginate/poly(acrylic acid) hydrogel beads as drug carriers for vancomycin release

In this study, hollow calcium–alginate/poly(acrylic acid) (PAA) hydrogel beads were prepared by UV polymerization for use as drug carriers. The hollow structure of the beads was fortified by the incorporation of PAA. The beads exhibited different swelling ratios when immersed in media at different pH values; this demonstrated that the prepared hydrogel beads were pH sensitive. A small amount (<9%) of vancomycin that had been incorporated into the beads was released in simulated gastric fluid, whereas a large amount (≤67%) was released in a sustained manner in simulated intestinal fluid. The observed drug‐release profiles demonstrated that the prepared hydrogel beads are ideal candidate carriers for vancomycin delivery into the gastrointestinal tract. Furthermore, the biological response of cells to these hydrogel beads indicated that they exhibited good biological safety and may have additional applications in tissue engineering. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Novel temperature and pH dual-sensitive PNIPAM/CMCS/MWCNT semi-IPN nanohybrid hydrogels: Synthesis,characterization, and DOX drug release

Novel poly(N-isopropylacrylamide)/carboxymethyl chitosan/multiwalled carbon nanotube semi-interpenetrating nanohybrid hydrogels were prepared, and the chemical structure and morphology were characterized. The prepared hydrogels showed temperature and pH dual-responsiveness, and the one containing multiwalled carbon nanotubes (MWCNTs)–COOH possessed high maximal swelling ratios. The phase transition produced at pH of 6.8–7.4 and temperature of 35–40°C, hinging on the system compositions and charge ratios. The hydrogels were used to load hydrophilic anticancer drug, with high entrapped efficiency of about 44%. The drug release changed with temperature, pH, and MWCNTs–COOH contents. The designed hydrogels can be used for site-specific target delivery of protein or hydrophilic anticancer drug.     

Thermally and magnetically dual‐responsive mesoporous silica nanospheres: preparation,characterization, and properties for the controlled release of sophoridine

Novel thermally and magnetically dual‐responsive mesoporous silica nanoparticles [magnetic mesoporous silica nanospheres (M‐MSNs)–poly(N‐isopropyl acrylamide) (PNIPAAm)] were developed with magnetic iron oxide (Fe₃O₄) nanoparticles as the core, mesoporous silica nanoparticles as the sandwiched layer, and thermally responsive polymers (PNIPAAm) as the outer shell. M‐MSN–PNIPAAm was initially used to control the release of sophoridine. The characteristics of M‐MSN–PNIPAAm were investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, thermogravimetry, N₂ adsorption–desorption isotherms, and vibrating specimen magnetometry analyses. The results indicate that the Fe₃O₄ nanoparticles were incorporated into the M‐MSNs, and PNIPAAm was grafted onto the surface of the M‐MSNs via precipitation polymerization. The obtained M‐MSN–PNIPAAm possessed superparamagnetic characteristics with a high surface area (292.44 m²/g), large pore volume (0.246 mL/g), and large mesoporous pore size (2.18 nm). Sophoridine was used as a drug model to investigate the loading and release properties at different temperatures. The results demonstrate that the PNIPAAm layers on the surface of M‐MSN–PNIPAAm effectively regulated the uptake and release of sophoridine. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40477.     

High throughput fiber reactor process for organic nanoparticle production: Poly(N‐isopropylacrylamide), polyacrylamide,and alginate

The goal of the present research was to scale microfluidic technology to a high throughput system using a fiber reactor platform. The nanoparticles studied are used in nanomedicine as drug delivery devices or “cages.” This process complements new research into skid‐based pharmaceutical production. Alginate nanoparticles were successfully generated in this process ranging in size from 23 to 151 nm with 424 g/day throughput. Polyacrylamide (PAm) nanoparticles were also formed and crosslinked with sizes ranging from 79 to 117 nm with 662 g/day throughput. Poly(N‐isopropylacrylamide) (PNIPAm) nanoparticles with a size range of 12 to 63 nm and 650 g/day were produced as well. Both one‐ and two‐phase flows were demonstrated. The effects of changes in various process parameters on the formed nanoparticle morphology are documented. Tunable process control is demonstrated to reliably manipulate the PNIPAm nanoparticle lower critical solution temperature. Process temperature affected the mean diameter and size dispersity of all the nanoparticles. This was postulated to be due to a shearing effect arising from carrier viscosity changes. Flow rate affected the average particle diameter by 10%–30%, and temperature could be used to tune the NP diameter by 50% across a moderate process temperature range of 5 to 25 °C. The PDI was very responsive to process temperature as well, decreasing by almost 50% across the same temperature range. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45524.     

Trimethyl Lock: A Multifunctional Molecular Tool for Drug Delivery,Cellular Imaging,and Stimuli‐Responsive Materials

Trimethyl lock (TML) systems are based on ortho‐hydroxydihydrocinnamic acid derivatives displaying increased lactonization reactivity owing to unfavorable steric interactions of three pendant methyl groups, and this leads to the formation of hydrocoumarins. Protection of the phenolic hydroxy function or masking of the reactivity as benzoquinone derivatives prevents lactonization and provides a trigger for controlled release of molecules attached to the carboxylic acid function through amides, esters, or thioesters. Their easy synthesis and possible chemical adaption to several different triggers make TML a highly versatile module for the development of drug‐delivery systems, prodrug approaches, cell‐imaging tools, molecular tools for supramolecular chemistry, as well as smart stimuliresponsive materials.     

Octacalcium Phosphate for Bone Tissue Engineering: Synthesis,Modification, and In Vitro Biocompatibility Assessment

Octacalcium phosphate (OCP, Ca₈H₂(PO₄)₆·5H₂O) is known to be a possible precursor of biological hydroxyapatite formation of organic bone tissue. OCP has higher biocompatibility and osseointegration rate compared to other calcium phosphates. In this work, the synthesis of low-temperature calcium phosphate compounds and substituted forms of those at physiological temperatures is shown. Strontium is used to improve bioactive properties of the material. Strontium was inserted into the OCP structure by ionic substitution in solutions. The processes of phase formation of low-temperature OCP with theoretical substitution of strontium for calcium up to 50 at.% in conditions close to physiological, i.e., temperature 35–37 °C and normal pressure, were described. The effect of strontium substitution range on changes in the crystal lattice of materials, the microstructural features, surface morphology and biological properties in vitro has been established. The results of the study indicate the effectiveness of using strontium in OCP for improving biocompatibility of OCP based composite materials intended for bone repair.     

Mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes: A review

The presence of a mucus layer that covers the surface of a variety of organs has been capitalized to develop mucoadhesive dosage forms that remain in the administration site for prolonged times, increasing the local and/or systemic bioavailability of the administered drug. The emergence of micro and nanotechnologies together with the implementation of non-invasive and painless administration routes has revolutionized the pharmaceutical market and the treatment of disease. Aiming to overcome the main drawbacks of the oral route and to maintain patient compliance high, the engineering of innovative drug delivery systems administrable by mucosal routes has come to light and gained the interest of the scientific community due to the possibility to dramatically change pharmacokinetics. In addition, to achieve the goal of mucosal drug administration, the development of biomaterials has been refined to fit specific applications. The present review initially describes the potential of nano-drug delivery systems conceived for mucosal administration by diverse non-parenteral routes (e.g., oral, inhalatory, etc.). Then, the benefit of the incorporation of mucoadhesive polymers into the structure of these innovative pharmaceutical products to prolong their residence time in the administration site and the release of the drug cargo will be discussed with focus in the developments of the last decade. In addition, the regulatory status of the most extensively used mucoadhesive polymers will be emphasized. Finally, a thorough overview of the different pharmaceutical applications of mucoadhesive polymers will be addressed.     

Fabrication of Cellulose Nanofiber/Reduced Graphene Oxide/Nitrile Rubber Flexible Films Using Pickering Emulsion Technology for Electromagnetic Interference Shielding and Piezoresistive Sensor

With the rapid development of flexible electronics, the demand for flexible electromagnetic interference (EMI) shielding materials is increasing. This study develops a new green and effective strategy, consisting of graphene oxide (GO) and cellulose nanofibrils (CNF) co-stabilized Pickering emulsion combined with hot-pressing technology, to prepare flexible and conductive nitrile rubber (NBR) composite films. The composite films consist of a 3D network conductive skeleton structure of reduced GO (RGO) and an isolated NBR structure. This specific design results in a maximum high conductivity of 99 S m⁻¹, which is higher by an order of magnitude compared with that of the composites obtained using the traditional solution blending method, and a stable EMI shielding effectiveness of 25.81 dB in the X band. The introduction of the flexible NBR results in the excellent flexibility and structural strength of the composite film, and exhibits a decrease of 2.51% in the EMI shielding efficacy after 5000 cycles. As a piezoresistive sensor for wearable devices, the CNF-RGO/NBR flexible film can hold precise current signals and respond to finger motion. The findings of this study can provide new insights for the design of conductive and flexible composites as wearable and portable medical equipment and electronic devices.