Synthesis and characterization of electroconductive hydrogels based on oxidized alginate and polypyrrole-grafted gelatin as tissue scaffolds.

Electroconductive biocompatible hydrogels with tunable properties have extensively been taken into account in tissue engineering applications due to their potential to provide suitable microenvironmental responses for the cells. In the present study, novel electroconductive hydrogels are designed and synthesized by reacting oxidized alginate with polypyrrole-grafted gelatin copolymer (PPy-g-gelatin) via formation of a Schiff-base linkage. The influence of the composition and the concentration of the components on the compressive modulus and functional performance of the hydrogels is investigated. The conductivity of the hydrogels measured by a two-probe method increased by increasing the level of polypyrrole-grafted gelatin, and a conductivity of 0.7753 S m-1 was exhibited by the hydrogel composed of 8% w/v polypyrrole-grafted gelatin (oxidized alginate:gelatin:polypyrrole-grafted gelatin; 30 : 35 : 35% v/v). The hydrogel compressive modulus was shown to be enhanced by increasing the total concentration of hydrogel. The characteristic features of the prepared hydrogels, including swelling ratio, volume fraction, cross-link density, and mesh size, are also studied and analyzed. Besides, the conductive hydrogels have a smaller mesh size and higher cross-link density than the non-conductive hydrogels. However, the hydrogels with high cross-link density, small mesh size, and large pore size presented higher electroconductivity as a result of easier movement of the ions throughout the hydrogel. These conductive hydrogels exhibited electrical conductivity and biodegradability with cell viability, implying potential as scaffolds for tissue engineering.

Microfluidic Directed Synthesis of Alginate Nanogels with Tunable Pore Size for Efficient Protein Delivery.

Alginate is a biopolymer with favorable pH-sensitive properties for oral delivery of peptides and proteins. However, conventional alginate nanogels have limitations such as low encapsulation efficiency because of drug leaching during bead preparation and burst release in high pH values. These shortcomings originate from large pore size of the nanogels. In this work, we proposed an on-chip hydrodynamic flow focusing approach for synthesis of alginate nanogels with adjustable pore size to achieve fine-tunable release profile of the encapsulated bioactive agents. It is demonstrated that the microstructure of nanogels can be controlled through adjusting flow ratio and mixing time directed on microfluidic platforms consisting of cross-junction microchannels. In this study, the average pore size of alginate nanogels (i.e., average molecular weight between cross-links, Mc) was related to synthesis parameters. Mc was calculated from equations based on equilibrium swelling theory and proposed methods to modify the theory for pH-sensitive nanogels. In the equations we derived, size and compactness of nanogels are key factors, which can be adjusted by controlling the flow ratio. It was found that increase in flow ratio increases the size of nanogels and decreases their compactness. The size of on-chip generated nanogels for flow ratio of 0.02-0.2 was measured to be in the range of 68-138 nm. Moreover, a method based on the Mie theory was implemented to estimate the aggregation number (Nagg) of polymer chains inside the nanogels as an indicator of compactness. According to the size and compactness results along with equations of modified swelling theory, Mc obtained to be in the range of 0.5-0.8 kDa. The proposed method could be considered as a promising approach for efficient polypeptides encapsulation and their sustained release.

Raspberry-like PLA/PGS biodegradable microparticles with urethane linkages: Unlocking tailored release of magnesium ions and oxygen for bone tissue engineering.

Designing biodegradable microparticles with finely controlled release properties for tissue engineering systems remains a significant scientific challenge. This study introduces a novel approach by fabricating urethane-linked PLA/PGS microparticles loaded with magnesium peroxide. The microparticles offer potential applications in bone tissue engineering due to their ability to provide a controlled release of oxygen and magnesium ions while maintaining physiological pH. The PGS pre-polymer was synthesized via polycondensation and characterized using FTIR, 1H NMR, and GPC. Microparticle morphology transformed from smooth to raspberry-like upon incorporation of PGS, as observed by SEM. Microparticle size was tuned by varying PGS and PLA concentrations. FTIR analysis confirmed the successful formation of urethane links within the microparticles. MgO2-loaded PLA/PGS microparticles exhibited sustained release of dissolved oxygen and magnesium ions for 21 days while maintaining physiological pH better than PLA microparticles. Cell viability assays confirmed microparticle cytocompatibility, and ALP and Alizarin red assays demonstrated their ability to induce osteogenic differentiation. These findings highlight the potential of pH-controlled MgO2-loaded microparticles as an effective system for bone tissue engineering. In conclusion, this study presents a novel approach to designing biodegradable microparticles with adjustable release properties for bone tissue engineering. The urethane-based MgO2-loaded microparticles provide controlled release of oxygen and magnesium ions and regulate the environment's pH, making them a promising system for bone tissue engineering applications.

The immune-stealth polymeric coating on drug delivery nanocarriers: In vitro engineering and in vivo fate.

Although essential nanosystems such as nanoparticles and nanocarriers are desirable options for transporting various drug molecules into the biological environment, they rapidly remove from the circulatory system due to their interaction with multiple in vivo barriers, especially the immune barrier, which will result in their short-term effects. In order to improve their effectiveness and durability in the circulatory system, the polymer coatings can use to cover the surface of nanoparticles and nanocarriers to conceal them from the immune system. Due to their different properties (like charge, elasticity, and hydrophilicity/hydrophobicity), these coatings can improve drug delivery nanosystem durability and therapeutic applications. The mentioned coatings have different types and are divided into various categories, such as synthetic polymers, polysaccharides, and zwitterionic polymers. Each of these polymers has unique properties based on its category, origin, and chemical structure that make them suitable for producing stealth drug delivery nanocarriers. In this review article, we have tried to explain the importance of these diverse polymer coatings in determining the fate of drug nanocarriers and then introduced the different types of these coatings and, finally, described various methods that directly and indirectly analyze the nanocoatings to determine the stability of nanoparticles in the body.

Enhanced neural differentiation by applying electrical stimulation utilizing conductive and antioxidant alginate-polypyrrole/poly-l-lysine hydrogels.

The challenge of restoration from neurodegenerative disorder requires effective solutions. To enhance the healing efficiencies, scaffolds with antioxidant activities, electroconductivity, and versatile features to encourage neuronal differentiation are potentially useful. Herein, polypyrrole-alginate (Alg-PPy) copolymer was used to design antioxidant and electroconductive hydrogels through the chemical oxidation radical polymerization method. The hydrogels have antioxidant effects to combat oxidative stress in nerve damage thanks to the introduction of PPy. Additionally, poly-l-lysine (PLL) provided these hydrogels with a great differentiation ability of stem cells. The morphology, porosity, swelling ratio, antioxidant activity, rheological behavior, and conductive characteristics of these hydrogels were precisely adjusted by altering the amount of PPy. Characterization of hydrogels showed appropriate electrical conductivity and antioxidant activity for neural tissue applications. Cytocompatibility, live/dead assays, and Annexin V/PI staining by flow cytometry using P19 cells confirmed the excellent cytocompatibility and cell protective effect under ROS microenvironment of these hydrogels in both normal and oxidative conditions. The neural marker investigation in the induction of electrical impulses was assessed through RT-PCR and immunofluorescence assay, demonstrating the differentiation of P19 cells to neurons cultured in these scaffolds. In summary, the antioxidant and electroconductive Alg-PPy/PLL hydrogels demonstrated excellent potential as promising scaffolds for treating neurodegenerative disorders.

Redox-Sensitive multifunctional hyaluronic acid-based nanomicelles with Fine-controlled anticancer drug release.

A significant contributor to cancer-related death globally is metastatic breast cancer. To reduce death rates, tumor-specific penetration and triggered drug release are crucial. Herein, targeted intracellular doxorubicin (Dox) delivery system was effectively prepared based on redox-sensitive hyaluronic acid-palmitoyl (HA-ss-PA) copolymers. The amphiphilic copolymers self-assembled into nano and showed outstanding drug-loading capacities and encapsulation efficiency for Dox. Micelles were stable under physiological conditions, but they quickly disintegrated in the presence of a reducing agent. The intracellular location of the fluorescent probe rhodamine b demonstrated that HA-ss-PA micelles are an efficient approach for drug delivery in breast cancer cells. Based on flow cytometry and live/dead assay, observations indicated that micelles induce apoptosis in both MCF-7 and MDA-MB-231 cells. In vivo evaluation in tumor-bearing mice confirmed that HA-ss-PA micelles exhibited excellent tumor-targeting activity. These findings imply that redox-sensitive HA-ss-PA micelles are promising candidates for use as intracellular delivery systems for hydrophobic anti-cancer drugs.

Controlled release of resveratrol from a composite nanofibrous scaffold: Effect of resveratrol on antioxidant activity and osteogenic differentiation.

Biocompatibility, mechanical strength, and osteogenesis properties of three-dimensional scaffolds are critical for bone tissue engineering. In addition, reactive oxygen species accumulate around bone defects and limit the activities of surrounding cells and bone formation. Therefore, the presence of an antioxidant in a bone tissue scaffold is also essential to address this issue. This study aimed to evaluate a composite nanofibrous scaffold similar to the natural extracellular matrix with antioxidant and osteogenic properties. To this end, polylactic acid (PLA)/organophilic montmorillonite (OMMT)/resveratrol (RSV) nanofibers were fabricated using the electrospinning method and characterized. RSV was used as an antioxidant, which promotes osteogenic differentiation, and OMMT was used as a mineral phase to increase the mechanical strength and control the release of RSV. The scaffolds' antioxidant activity was measured using DPPH assay and found 83.75% for PLA/OMMT/RSV nanofibers. The mechanical strength was increased by adding OMMT to the neat PLA. The biocompatibility of the scaffolds was investigated using an MTT assay, and the results did not show any toxic effects on human adipose mesenchymal stem cells (hASCs). Moreover, the Live/Dead assay indicated the appropriate distribution of live cells after 5 days. Cell culture results displayed that hASCs could adhere and spread on the surface of composite nanofibers. Meanwhile, the level of alkaline phosphatase, osteocalcin, and osteopontin was increased for hASCs cultured on the PLA/OMMT/RSV nanofibrous scaffold. Therefore, this study concludes that the RSV-loaded composite nanofibers with antioxidant and osteogenesis properties and appropriate mechanical strength can be introduced for bone tissue regeneration applications.

Electroactive and antioxidant injectable in-situ forming hydrogels with tunable properties by polyethylenimine and polyaniline for nerve tissue engineering.

The injectable in-situ forming electroconductive hydrogels with antioxidant activity are promising candidates for nerve tissue engineering. In this study, we synthesized and developed a gelatin-graft-polyaniline/periodate-oxidized alginate hydrogel through the introduction of branched polyethylenimine (PEI) to improve the rheological properties. Moreover, antioxidant property, electroconductivity and the effect of external electrical stimulus on the nerve cell behavior were investigated. The results showed that by increasing the polyaniline content, the antioxidant activity, pore sizes, and swelling ratio of the hydrogel were increased, while the crosslinking density and storage modulus were decreased. The introduction of PEI accelerated the gelation time, decreased swelling ratio and pore size, and increased the storage modulus and crosslinking density. Cell studies showed that all formulations had supported the viability of P19 embryonic carcinoma cells with the neuritis elongation in the presence of the external electrical-stimulus. Gene expression of the neuronal markers, including Nestin, Pax-6, and ß-tubulin III, was increased in all hydrogels; In addition, electrical stimulation significantly elevated the expression of these markers in high polyaniline-content hydrogel compared to the polyaniline-free hydrogel. In conclusion, the results suggest that the prepared injectable electroconductive hydrogels can be a promising approach for neural tissue engineering.

A bifunctional electrospun nanocomposite wound dressing containing surfactin and curcumin: In vitro and in vivo studies.

A double-nozzle electrospinning technique was adopted in the present study to yield a novel bifunctional wound dressing composed of curcumin (Cur) and surfactin (Sur)-loaded poly(ε-caprolactone) (PCL)-gelatin (Gel). To comprehensively unveil the effect of both composition and drug molecules on the applicability, different dressings composed of PCL, Gel, and combination of the polymers with the drug molecules were fabricated. Besides the physicochemical properties, the in vitro and in vivo biological properties of prepared wound dressings were assessed. The results showed that increasing in the Cur from 0 to 3% (w/w) and Sur from 0 to 0.2 mg/mL caused a decrease in the elastic modulus on the one hand. On the other hand, the tensile strength and elongation at break experienced an increase in their values. The wettability, swelling capacity, and degradation rate of PCL improved significantly when both Gel and the drug molecules had been added. The dressings encompassing Sur (0.2 mg/mL) exhibited an excellent antibacterial activity after 24 h (>99%). Moreover, a sustained release of Cur up to 14 days was obtained. The in vitro cell compatibility tests implied a desirable result for all dressings without taking the composition into consideration. To complement the in vitro studies, the PCL/0.2Sur-Gel/3%Cur dressing was further assessed in vivo and the results revealed a significant improvement in the healing rate compared to control groups proofing its great potential for accelerated wound healing applications.

Fabrication of amine-decorated nonspherical microparticles with calcium peroxide cargo for controlled release of oxygen.

Oxygen is an important signaling molecule which affects many behaviors of bone progenitor cells. Oxygen releasing biomaterials depend on their material and design are able to provide and modulate the desired oxygen for cells. To date, many oxygen releasing vehicles have been developed by incorporating microsized calcium peroxide (CPO) into polymeric matrixes. However, an oxygen releasing system based on nano CPO is still lacking. Not only can nanosized CPO provide more controllable oxygen release, but also can be loaded in vehicles of different shapes and sizes. Current research was conducted to take the advantages of nanomaterials as oxygen releasing components. To this end, CPO nanoparticles were synthesized using a hydrolysis-precipitation procedure and then loaded into the poly (lactide-co-glycolide) (PLGA) matrix via an electrospray process. The surface of PLGA/CaO2 particles was decorated with amine functionalities to render them more bioactive through a controlled aminolysis reaction. The studies on PLGA/CaO2 microparticles revealed that biconcave disk-like morphology with a mean diameter of 5.3 µm was formed. The particles persistently provide oxygen content of 35-67.5 mmHg up to 14 days which lies within the acceptable range for bone tissue engineering applications. PLGA/CaO2 microparticles induced 208 and 76% increase in number of viable mesenchymal cells on 6th and 14th days of cell seeding comparing PLGA counterparts. Furthermore, the expression of two bone biomarkers, that is, alkaline phosphatase and osteocalcin, at protein level as well as the extent of calcium deposition was increased in the presence of PLGA/CaO2 microparticles compared to PLGA ones.

Oxygen-releasing nanofibers for breathable bone tissue engineering application.

Oxygen is a vital molecule for cell and tissue processes. Electrospun fibers have been extensively used as drug loading carriers due to possibility of well control over drug release with modulating fiber properties. However, they have not been used as depots for oxygen release. In the present study, an oxygen-releasing nanofibrous scaffold has been developed by electrospinning of polylactic acid/nano-calcium peroxide suspension with different polylactic acid concentrations (6.5 and 13% w/v). The electrospun fibers with calcium peroxide cargo provided oxygen content of 30-94 mmHg in a period of 14 days which lies well within the oxygen level of osseous tissue. The release profile of 13% polylactic acid fibers was different with that of 6.5% fibers with respects to the initial content of released oxygen and the release rate. Not only did 13% fibers supply oxygen with a slower rate, but also they resulted in a lower burst release of oxygen. Cell culture studies in hypoxia corroborated that 13% polylactic acid fibers better preserve cell viability comparing 6.5% counterparts as perceived by MTT assay. Moreover, they endowed more favored milieu for adherence, arrangement and migration of mesenchymal stem cells as confirmed by microscopy images. The oxygen-releasing fibers equally affected alkaline phosphatase, osteocalcin, and calcium deposition by mesenchymal stem cells most likely due to interplay between topographical and metabolic cues offered by 6.5 and 13% formulations.

Development of an oxygen-releasing electroconductive in-situ crosslinkable hydrogel based on oxidized pectin and grafted gelatin for tissue engineering applications.

Injectable hydrogels with conductivity are highly desirable as scaffolds for the engineering of various electrical stimuli-responsive tissues, including nerve, muscle, retina, and bone. However, oxygen deprivation within scaffolds can lead to failure by causing cell necrosis. Therefore, an oxygen release conductive injectable hydrogel can serve as a promising support for the regeneration of such tissues. In the present study, H2O2-loaded polylactic acid microparticles were fabricated. Then, gelatin-graft-polypyrrole with various pyrrole contents and periodate-oxidized pectin were synthesized, and consequently, injectable conductive hydrogel/microparticle scaffolds, inside which catalase was grafted and trapped, were obtained. The results revealed that spherical particles with a mean diameter of 60.39 µm and encapsulation efficiency of 49.64 %, which persistently provided oxygen up to 14 days, were achieved. Investigations on hydrogels revealed that with the increase of pyrrole content of gelatin-graft-polypyrrole from 0 to 15 %, the swelling ratio, pore size, porosity, and conductivity were increased from 6.5 to 11.8, 173.13 µm-295.96 µm, 79.7%-93.8%, and from 0.06 mS/m to 2.14 mS/m, respectively. On the other hand, the crosslinking degree and compressive modulus of hydrogels were shown to decrease from 67.24%-27.35%, and from 214.1 kPa to 64.4 kPa, respectively. Moreover, all formulations supported cell viability and attachment. Overall, the hydrogel/particle scaffold with the merits of electrical conductivity, injectability, compatibility, and sustained oxygen release can be used as a tissue engineering scaffold, promoting the regeneration of electricity responsive tissues. Considering all the aforementioned characteristics and behavior of the fabricated scaffolds, they may be promising candidates for bone tissue engineering applications.

Size effect of human epidermal growth factor-conjugated polystyrene particles on cell proliferation.

Conjugation of growth factors to a carrier is a favorable method to improve their efficacy as therapeutic molecules. Here, we report the carrier size effect on bioactivity of human epidermal growth factor (hEGF) conjugated to polystyrene particles. BALB/3T3 cells were treated with hEGF-conjugated particles (hEGF-conjs) sized from 20 to 1000 nm. At hEGF concentrations less than 0.5 ng ml-1, free hEGF was more potent than the hEGF-conjs at inducing cell proliferation. However, cell proliferation was size-dependent at higher concentrations of hEGF i.e. hEGF-conjs sized equal to or less than 200 nm displayed lower cell proliferation, compared to free hEGF, but larger particles showed increased cell proliferation. This is in agreement with previous studies showing accumulation of activated-EGFRs in early endosomes triggers apoptosis of A431 and HeLa cells. The confocal microscopy and co-localization fluorescence staining showed the 500 and 1000 nm hEGF-conjs exclusively remained on the cell surface, probably enabling them to activate EGF receptors for a longer time. Conversely, smaller particles were mostly inside the cells, indicating their rapid endocytosis. Similarly, A431 cells treated with 20 nm hEGF-conj, endocytosed the particles and experienced decreased cell proliferation, while the 500 and 1000 nm hEGF-conjs were not internalized, and induced partial cell proliferation. Moreover, we showed multivalency of hEGF-conjs is not the cause of enhanced cell proliferation by large particles, as the degree of EGFR phosphorylation by free EGF was higher, compared to hEGF-conjs. Our results suggest the potential of micron-sized particles as a carrier for hEGF to enhance cell proliferation, which could be explored as a promising approach for topical application of growth factors for accelerating wound healing.

Development of a simvastatin loaded injectable porous scaffold in situ formed by phase inversion method for bone tissue regeneration.

INTRODUCTION:: The use of injectable scaffolds as a minimally invasive method is a good choice in tissue engineering applications. A critical parameter for the tissue engineering scaffolds is a suitable morphology with interconnected pores. We present the development of a simvastatin loaded scaffold that forms in situ and provides the porous structure with interconnected pores. METHODS:: The formulation of these scaffolds includes a polymeric solution of poly lactic-co-glycolic acid (25 wt%) in N-methyl-2-pyrrolidone containing 6 wt% deionized water and porogen (mannitol, four times the weight of the polymer). We have grafted simvastatin to poly lactic-co-glycolic acid by the esterification reactions. Simvastatin or simvastatin-grafted poly lactic-co-glycolic acid in different levels was added to polymer solution and finally the solution was injected into phosphate buffered saline. The simvastatin-grafted poly lactic-co-glycolic acid was characterized by attenuated total reflection Fourier-transform infra-red and 1H-nuclear magnetic resonance spectroscopy. The morphology, porosity, and biocompatibility of the scaffolds were evaluated. The in vitro simvastatin release from the various formulations was studied. Osteogenic differentiation of the adipose-derived stem cells was investigated using alkaline phosphatase activity assay and cell mineralization was evaluated using Alizarin red staining. RESULTS:: The morphology results showed the resultant scaffold was porous with the interconnected pores. The scaffolds presented 91% porosity. Non-toxic doses of simvastatin in the scaffolds were determined by methyl-thiazolyl diphenyl-tetrazolium bromide assay. The released simvastatin from the scaffolds continues over 80 days. Alkaline phosphatase activity and Alizarin red results indicated that cell osteogenic differentiation is promoted. CONCLUSION:: The results demonstrated that release of simvastatin from the injectable scaffolds can have positive effects on osteogenic differentiation of the adipose-derived stem cells.

Hydrogel/fiber conductive scaffold for bone tissue engineering.

Hydrogel/fiber composites have emerged as compelling scaffolds for regeneration purposes. Any biorelated modification or feature may endow more regenerative functionality to these composites. In the present study, a hydrogel/fiber scaffold possessing electrical conductivity in both phases, hydrogel and fiber, has been prepared and evaluated. Fiber component possessed electrical conductivity due to the presence of polyaniline (PANi) and hydrogel fraction thanks to the presence of graphene nanoparticles. PANi based fibers were processed through electrospinning and transformed into a three-dimensional structure through ultrasonication. The hydrogel precursor solution composed of oxidized polysaccharides, gelatin and graphene with predesigned ratio was added to fibers and left to gel. The results of assessments on pristine hydrogel and hydrogel/fiber denoted that inclusion of conducting fibers into hydrogel increased elastic modulus, roughness and electrical conductivity, whereas decreased hydrophilicity. Moreover, the results showed that hydrogel/fiber composite better supported human osteoblast-like cell adhesion, proliferation, and morphology comparing hydrogel alone. In a nutshell, the presence of gel/fiber architecture along with electrical conductivity may lead the scaffold to be very promising for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 718-724, 2018.

Particle-coated electrospun scaffold: A semi-conductive drug eluted scaffold with layered fiber/particle arrangement.

In this study, an antibacterial fiber/particle scaffold with improved hydrophilicity has been fabricated. To this end, polyaniline (PANi)/polycaprolactone (PCL) was processed to fibers via electrospinning. Thereafter, ciprofloxacin was loaded in oxidized alginate/gelatin mixture. The mixture was then electrosprayed onto PANi-based fibers. After particle solidification, oxidized alginate and gelatin simultaneously were crosslinked and encapsulated the ciprofloxacin. The particle/fiber scaffold enabled controlled release of ciprofloxacin. Moreover, the scaffold offered a semi-conductive structure in which the conductive fibers were interrupted by insulating particles. The scaffold proved higher hydrophilicity, better cell adhesion and proliferation compared with the pristine fibers. Furthermore, the scaffold demonstrated extensive antibacterial activity against gram positive and gram negative bacteria tested. The construct with layered fiber/particle arrangement and benefited from electrical semi-conductivity, relevant surface hydrophilicity and controlled release of an antibacterial component can be a potent nerve tissue engineering scaffold. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3248-3254, 2018.

Self-crosslinking effect of chitosan and gelatin on alginate based hydrogels: Injectable in situ forming scaffolds.

Injectable in situ forming hydrogels has great potential in tissue engineering. Simple and easy preparation of these hydrogels with low toxicity and stability is a great advantage. In the present study, two types of self-crosslinking in situ forming alginate based hydrogels with different formulation were synthesized, characterized and compared in order to introduce an optimal injectable scaffold in minimally invasive applications in tissue engineering. To this end, the hydrogels consist of oxidized alginate (AD), polyethylene glycol (PEG) and carboxymethyl chitosan (CMC) or gelatin (GEL) was synthesized. The hydrogels were assessed by many techniques including microscopy, spectroscopy, compressive analysis, injectability, rheological analysis and cell viability to ascertain hydrogel properties. In comparison with AD/PEG-GEL hydrogel, AD/PEG-CMC hydrogel showed a higher compressive modulus, viscosity and injection time, whereas AD/PEG-GEL hydrogel displayed a higher degree of crosslinking. Due to the rheological behavior of AD/PEG-CMC hydrogel, this composition was more suitable for the injectable application. The hydrogels, despite the composition, showed the ability to survive and proliferate mesenchymal stem cells based on cytotoxicity assays. With respect to rheological, degradation time and compressive properties of the above-mentioned hydrogels, AD/PEG-CMC hydrogel could be considered as an appropriate candidate for injectable self-crosslinking application in tissue engineering.

Effect of PEDOT:PSS in tissue engineering composite scaffold on improvement and maintenance of endothelial cell function.

According to recent research, smart polymers can affect different kind of mammalian cells such as endothelial cells. It is known that conductive polymers have great features, e.g. electrical conductivity, and can help increase electrical cell communication. To clarify the effect of one of these smart materials on endothelial cells, which are not inherently electrically dependent, poly(3, 4-ethylene dioxythiophene) polystyrene sulfonate (PEDOT:PSS) was chosen. Scaffolds were composed of gelatin, alginate, and PEDOT:PSS and made through solvent casting. Human umbilical vein endothelial cells (HUVECs) were cultured on the scaffold with different PEDOT:PSS concentrations. SEM, MTT assay, cell attachment, nitric oxide measurement, real-time PCR and immunohistochemistry analysis were employed to assess endothelial cell responses. Although there was no significant difference in swelling ratio, mass loss, and cell attachment when PEDOT:PSS concentration increased in scaffold construction, cell proliferation noticeably increased after seven days. The cells showed a significant increase in proliferation and NO release to the scaffold with 1% PEDOT:PSS concentration. The results indicated increases in the amount of expression of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), kinase insert domain receptor (KDR), vascular-endothelial Cadherin (VE. Cadherin), and von Will brand factor (vWf) in the group which contained a conductive polymer in comparison with the non-conductive scaffold. Therefore, as a conductive polymer, PEDOT:PSS can affect the endothelial cell behaviours.

Electrically conductive gel/fibers composite scaffold with graded properties.

Gradient biomaterials have emerged as fascinating platforms to satisfy the need for imitation of ubiquitous gradients in biology, especially those found at tissue interfaces. In the current study, a gradient fiber-hydrogel scaffold was fabricated to imitate the extracellular matrix of soft-to-hard tissue interfaces. For the fiber proportion, a gradient electrospinning was developed where controlled mixing of solutions with dissimilar concentration of a conductive polymer in injection vessel imparted a composition gradient to electrospinning jet, and thus electrospun fibers. The planar graded fibers were exposed to ultrasound to be three-dimensional and gel permeable. For the hydrogel fraction, a gradient mixing tool was used in which controlled mixing of solutions with disparate concentration of hydrogel components conferred a composition gradient to hydrogel precursor solution. The graded precursor solution was introduced to gradient 3D fibers and then self-crosslinked. Gradient fibers, hydrogel and fiber-gel composite were assessed by many techniques including microscopy, spectroscopy, mechanical analysis and conductivity measurement to ascertain gradient formation. Polymeric constituents' gradient in electrospinning outflow gave rise to not only gradual changes in fiber diameter, also subtle variations in electrical conductivity and other fibers' attributes. Gradient hydrogel making apparatus rendered a steady increase in crosslink involving component and yielded a hydrogel with graded features. The created composite revealed the propitious unification of fibrous and gelation parts into a single scaffold with no detrimental effect on structure and gradient of each part.

Injectable conductive collagen/alginate/polypyrrole hydrogels as a biocompatible system for biomedical applications.

Recently, Injectable Conducting Hydrogel (ICH) systems have gained much attention for tissue engineering and regenerative medicine. These systems can promote the regeneration of tissues responding to electrical responses. In this study, a novel ICH system was introduced. To achieve this system, firstly, a soluble non-toxic polypyrrole (PPy) synthesized by grafting pyrrole on alginate (Alg) backbone (Alg-graft-PPy), and then, ICH systems were prepared by the given ratios of Alg-graft-PPy, Alg, and collagen (Col). Three different amounts of Col (0.5, 1, and 1.5 mg/ml) were added to the system including Alg-graft-PPy: Alg wt. % with the ratios of 20:80 and 30:70. FTIR spectroscopy, electrical conductivity, viscosity, syringeability, gelation time, and MTT assay were performed in order to characterize the produced hydrogels. Due to the rheological behavior of 20:80 (Alg-graft-PPy: Alg wt. %), it was recognized more suitable to inject. Also this system associated with 0.5 mg/ml Col introduced as the best sample with respect to its viscosity and injectability. This ICH system has shown high conductivity in addition to a good level of cell viability and syringeability. With respect to properties of the produced ICH system, it can be applied for bone, nerve, muscle and cardiac cells, which respond to electrical impulses.