Dual Functional Antibacterial-Antioxidant Core/Shell Alginate/Poly(ε-caprolactone) Nanofiber Membrane: A Potential Wound Dressing.

Core/shell nanofibers offer the advantage of encapsulating multiple drugs with different hydrophilicity in the core and shell, thus allowing for the controlled release of pharmaceutic agents. Specifically, the burst release of hydrophilic drugs from such fiber membranes causes an instantaneous high drug concentration, whereas a long and steady release is usually desired. Herein, we tackle the problem of the initial burst release by the generation of core/shell nanofibers with the hydrophilic antibiotic drug gentamycin loaded within a hydrophilic alginate core surrounded by a hydrophobic shell of poly(ε-caprolactone). Emulsion electrospinning was used as the nanofibrous mesh generation procedure. This process also allows for the loading of a hydrophobic compound, where we selected a natural antioxidant molecule, betulin (BTL), to detoxify the radicals. The resulting nanofibers exhibited a cylindrical shape with a core/shell structure. In vitro tests showed a controlled release of gentamicin from nanofibers via diffusion. The drug reached 93% release in an alginate hydrogel film but only 50% release in the nanofibers, suggesting its potential to minimize the initial burst release. Antibacterial tests revealed significant activity against both Gram-negative and Gram-positive bacteria. The antioxidant property of betulin was confirmed through the DPPH assay, where the incorporation of 20% BTL revealed 37.3% DPPH scavenging. The nanofibers also exhibited favorable biocompatibility in cell culture studies, and no harmful effects on cell viability were observed. Overall, this research offers a promising approach to producing core/shell nanofibrous mats with antibacterial and antioxidant properties, which could effectively address the requirements of wound dressings, including infection prevention and wound healing acceleration.

Multifunctional Casein-Based Wound Dressing Capable of Monitoring and Moderating the Proteolytic Activity of Chronic Wounds.

Every 1.2 s, a diabetic foot ulcer is developed, and every 20 s, one amputation is carried out in diabetic patients. Monitoring and controlling protease activity have been considered as a strategy for more efficient management of diabetic and other chronic wounds. This study aimed to develop a casein-based dressing that, by its disappearance, provides information about the activity of proteases and simultaneously harnesses proteolytic activity. Casein films were fabricated by using an aqueous solution, and heat treatment was successfully deployed as a green and clean approach to confer hydrolytic stability. Our results showed that casein-based films' mechanical characteristics, water absorption, and proteolytic stability could be controlled by the length of the heat treatment, which proved to be a useful tool. An increase in the treatment duration from 30 min to 3 h led to toleration of 2.4 times higher stress, 2 times lower water uptake, and 3.4 times higher proteolytic stability at examined conditions. Selected casein-based structures responded to Bacillus sp. bacteria's protease (BSP) and human neutrophil elastase (HNE) as representatives of bacterial and nonbacterial proteases found in the wounds at 10 and 200 ng mL-1 levels, respectively. The hydrolysis was accompanied by a 36% reduction in proteolytic activity measured by using a casein-based universal protease activity assay. The released casein fragments could scavenge 90% of the examined radicals. In-vitro cell culture studies showed that the hydrolysates were not cytotoxic, and the casein-based film had a favorable interaction with fibroblast cells, indicating its potential as a scaffold in the case that proteolytic activity would not be to the extent that causes its rapid disintegration. In general, these findings hold promise for applying the developed casein-based structure for detecting proteolytic activity without the need for any equipment, kits, or expertise and, more importantly, in a highly economical manner. In the case that the proteolytic activity would not be severe, it could also serve as a substrate for cell adhesion and growth; this would aid in the healing process.

Anthocyanin/Honey-Incorporated Alginate Hydrogel as a Bio-Based pH-Responsive/Antibacterial/Antioxidant Wound Dressing.

Infection is a major problem that increases the normal pH of the wound bed and interferes with wound healing. Natural biomaterials can serve as a suitable environment to acquire a great practical effect on the healing process. In this context, anthocyanin-rich red cabbage (Brassica oleracea var. capitata F. rubra) extract and honey-loaded alginate hydrogel was fabricated using calcium chloride as a crosslinking agent. The pH sensitivity of anthocyanins can be used as an indicator to monitor possible infection of the wound, while honey would promote the healing process by its intrinsic properties. The mechanical properties of the hydrogel film samples showed that honey acts as a plasticizer and that increasing the incorporation from 200% to 400% enhances the tensile strength from 3.22 to 6.15 MPa and elongation at break from 0.69% to 4.75%. Moreover, a water absorption and retention study showed that the hydrogel film is able to absorb about 250% water after 50 min and retain 40% of its absorbed water after 12 h. The disk diffusion test showed favorable antibacterial activity of the honey-loaded hydrogel against both Gram-positive and Gram-negative Staphylococcus aureus and Escherichia coli, respectively. In addition, the incorporation of honey significantly improved the mechanical properties of the hydrogel. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay proved the antioxidant activity of the honey and anthocyanin-containing hydrogel samples with more than 95% DPPH scavenging efficiency after 3 h. The pH-dependent property of the samples was investigated and recorded by observing the color change at different pH values of 4, 7, and 9 using different buffers. The result revealed a promising color change from red at pH = 4 to blue at pH = 7 and purple at pH = 9. An in vitro cell culture study of the samples using L929 mouse fibroblast cells showed excellent biocompatibility with significant increase in cell proliferation. Overall, this study provides a promising start and an antibacterial/antioxidant hydrogel with great potential to meet wound-dressing requirements.

Effect of Increased Powder-Binder Adhesion by Backbone Grafting on the Properties of Feedstocks for Ceramic Injection Molding.

The good interaction between the ceramic powder and the binder system is vital for ceramic injection molding and prevents the phase separation during processing. Due to the non-polar structure of polyolefins such as high-density polyethylene (HDPE) and the polar surface of ceramics such as zirconia, there is not appropriate adhesion between them. In this study, the effect of adding high-density polyethylene grafted with acrylic acid (AAHDPE), with high polarity and strong adhesion to the powder, on the rheological, thermal and chemical properties of polymer composites highly filled with zirconia and feedstocks was evaluated. To gain a deeper understanding of the effect of each component, formulations containing different amounts of HDPE and or AAHDPE, zirconia and paraffin wax (PW) were prepared. Attenuated total reflection spectroscopy (ATR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and rotational and capillary rheology were used for the characterization of the different formulations. The ATR analysis revealed the formation of hydrogen bonds between the hydroxyl groups on the zirconia surface and AAHDPE. The improved powder-binder adhesion in the formulations with more AAHDPE resulted in a better powder dispersion and homogeneous mixtures, as observed by SEM. DSC results revealed that the addition of AAHDPE, PW and zirconia effect the melting and crystallization temperature and crystallinity of the binder, the polymer-filled system and feedstocks. The better powder--binder adhesion and powder dispersion effectively decreased the viscosity of the highly filled polymer composites and feedstocks with AAHDPE; this showed the potential of grafted polymers as binders for ceramic injection molding.

Emulsion electrospinning of sodium alginate/poly(ε-caprolactone) core/shell nanofibers for biomedical applications.

Electrospun nanofibers have shown great potential as drug vehicles and tissue engineering scaffolds. However, the successful encapsulation of multiple hydrophilic/hydrophobic therapeutic compounds is still challenging. Herein, sodium alginate/poly(ε-caprolactone) core/shell nanofibers were fabricated via water-in-oil emulsion electrospinning. The sodium alginate concentration, water-to-oil ratio, and surfactant concentration were optimized for the maximum stability of the emulsion. The results demonstrated that an increasing water-to-oil ratio results in more deviation from Newtonian fluid and leads to a broader distribution of the fibers' diameters. Moreover, increasing poly(ε-caprolactone) concentration increases loss and storage moduli and increases the diameter of the resulting fibers. The nanofibers' characteristics were investigated by scanning electron microscopy, transmission electron microscopy, confocal laser scanning microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and water contact angle measurements. It was observed that using an emulsion composition of 10% (w/v) PCL and a water-to-oil ratio of 0.1 results in smooth, cylindrical, and uniform core/shell nanofibers with PCL in the shell and ALG in the core. The in vitro cell culture study demonstrated the favorable biocompatibility of nanofibers. Overall, this study provides a promising and trustworthy material for biomedical applications.

Control of drug release from cotton fabric by nanofibrous mat.

A drug delivery system (DDSs) was developed in the present study based on textile substrates as drug carriers and electrospun nanofibers as a controller of release rate. Three types of drugs consisting of ciprofloxacin (CIP), clotrimazole (CLO), and benzalkonium chloride (BEN) were loaded into the cover glass (CG) and cotton fabrics (CF1 and CF2) separately. Then, the drug-loaded substrates were coated with polycaprolactone (PCL) and polycaprolactone/gelatin (PCL/Gel) nanofibers with various thicknesses. The morphology and hydrophilicity of the electrospun nanofibers and the release profile of drug-loaded samples were investigated. FTIR, XRD, and in vitro biodegradability analysis were analyzed to characterize the drug delivery system. A morphological study of electrospun fibers showed the mean diameter of the PCL and PCL/Gel nanofibers 127 ± 25 and 178 ± 38 nm, respectively. The drug delivery assay revealed that various factors affect the rate of drug releases, such as the type of drug, the type of drug carrier, and the thickness of the covered nanofibers. The study highlights the ability of drugs to load substrates with coated nanofibers as controlled drug delivery systems. In conclusion, it is shown that the obtained samples are excellent candidates for future wound dressing applications.

Improved wound healing of diabetic foot ulcers using human placenta-derived mesenchymal stem cells in gelatin electrospun nanofibrous scaffolds plus a platelet-rich plasma gel: A randomized clinical trial.

AIM: The effectiveness of nanofibers containing human placenta-derived mesenchymal stem cells (hPDMSCs) plus platelet-rich plasma (PRP) for healing of diabetic foot ulcers (DFUs) was investigated. METHODS: hPDMSCs were isolated from human donor placentas, and cultured in electrospun gelatin nanofibrous scaffolds (GNS). Twenty-eight patients with DFUs were randomized into three groups in a 12-week trial: (A) Treated with hPDMSCs; (B) Treated with hPDMSCs after coating the ulcer with PRP gel; (C) Control group received standard wound care. Wound area and pain freewalkingdistance were measured every 2 weeks. RESULTS: Flow cytometry showed the expression of mesenchymal markers. SEM images and DAPI staining indicated significantly higher levels of hPDMSC proliferation on GNS after 3 and 7 days of culture. The MTS assay showed a significant increase in proliferation on GNS, compared to controls. Wound size reduction was 66% in group A, 71% in group B, and 36% in control group C. A significant difference in wound closure and pain-free walking distance was observed between groups A and B, compared to control group C (p < 0.05), but no difference between groups A and B. Biopsy of the implanted tissue showed the development of new capillary formation in groups A and B. CONCLUSION: Implantation of hPDMSCs in GNS accelerated wound healing and improved clinical parameters in DFU patients.

Fabrication, characterization and cytocompatibility assessment of gelatin nanofibers coated with a polymer thin film by initiated chemical vapor deposition.

The presence of various functional groups in the structure of gelatin nanofibers (GNFs) has made it a suitable candidate for biomedical applications, yet its fast dissolution in aqueous media has been a real challenge for years. In the present work, we propose an efficient procedure to improve the durability of the GNFs. The electrospun GNFs were coated with poly(ethylene glycol dimethacrylate) (pEGDMA) using initiated chemical vapor deposition (iCVD) as a completely dry polymerization method. Morphological and chemical analysis revealed that an ultrathin layer formed around nanofibers (iCVD-GNFs) which has covalently bonded to gelatin chains. Against the instant dissolution of GNFs, the in vitro biodegradability test showed the iCVD-GNFs, to a large extent, preserve their morphology after 14 days of immersion and did not lose its integrity even after 31 days. In vitro cell culture studies, also, revealed cytocompatibility of the iCVD-GNFs for human fibroblast cells (hFC), as well as higher cell proliferation on the iCVD-GNFs compared to control made from tissue culture plate (TCP). Furthermore, contact angle measurements indicated that the hydrophilic GNFs became hydrophobic after the iCVD, yet FE-SEM images of cell-seeded iCVD-GNFs showed satisfactory cell adhesion. Taken together, the proposed method paves a promising way for the production of water-resistant GNFs utilized in biomedical applications; for instance, tissue engineering scaffolds and wound dressings.

Differentiation of Human Scalp Adipose-Derived Mesenchymal Stem Cells into Mature Neural Cells on Electrospun Nanofibrous Scaffolds for Nerve Tissue Engineering Applications.

OBJECTIVES: This study aimed to isolate and culture SADS cells, investigate their neurogenic capacity and evaluate their application for nerve tissue engineering. MATERIALS AND METHODS: In this experimental study, SADS cells were isolated from human adipose tissue. After 7-day treatment of SADS cells with insulin, indomethacin and isobutylmethylxanthine, neurogenic differentiation of SADS cells was investigated. During this study, Poly (ε-caprolactone) (PCL) and PCL/gelatin nanofibrous scaffolds were fabricated using electrospinning and subsequently nanofibrous scaffolds were coated with platelet-rich plasma (PRP). SADS cells were also seeded on nanofibrous scaffolds and neurogentic differentiation of these cells on nanofibers was also evaluated. Effect of PRP on proliferation and differentiation of SADS cells on scaffolds was also studied. RESULTS: Our results showed that after 7-day treatment of SADS cells with insulin, indomethacin and isobutylmethylxanthine, SADS cells expressed markers characteristic of neural cells such as nestin and neuron specific nuclear protein (NEUN) (as early neuronal markers) as well as microtubule-associated protein 2 (MAP2) and neuronal microtubule-associated (TAU) (as mature neuronal markers) while mature astrocyte maker (GFAP) was not expressed. MTT assay and SEM results showed that incorporation of gelatin and PRP into the structure of nanofibrous scaffolds has a significant positive influence on the bioactivity of scaffolds. Our results also showed neurogentic differentiation of SADS cells on scaffolds. CONCLUSIONS: Our results demonstrated that SADS cells have potential to differentiate into early and mature progenitor neurons, in vitro. PCL/gelatin/PRP was found to be a promising substrate for proliferation of SADS cells and differentiation of these cells into neural cells which make these scaffolds a candidate for further in vivo experiments and suggest their application for nerve tissue engineering.

Development of electrospun poly (vinyl alcohol)-based bionanocomposite scaffolds for bone tissue engineering.

The article is focused on the role of nanohydroxy apatite (nHAp) and cellulose nanofibers (CNFs) as fillers in the electrospun poly (vinyl alcohol) (ES-PVA) nanofibers for bone tissue engineering (TE). Fibrous scaffolds of PVA, PVA/nHAp (10 wt.%), and PVA/nHAp(10 wt.%)/CNF(3 wt.%) were successfully fabricated and characterized. Tensile test on electrospun PVA/nHAp10 and PVA/nHAp10/CNF3 revealed a three-fold and seven-fold increase in modulus compared with pure ES-PVA (45.45 ± 4.77). Although, nanofiller loading slightly reduced the porosity percentage, all scaffolds had porosity higher than 70%. In addition, contact angle test proved the great hydrophilicity of scaffolds. The presence of fillers reduced in vitro biodegradation rate in PBS while accelerates biomineralization in simulated body fluid (SBF). Furthermore, cell viability, cell attachment, and functional activity of osteoblast MG-63 cells were studied on scaffolds showing higher cellular activity for scaffolds with nanofillers. Generally, the obtained results confirm that the 3-componemnt fibrous scaffold of PVA/nHAp/CNF has promising potential in hard TE. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1111-1120, 2018.

Fabrication, characterization, and biocompatibility assessment of a novel elastomeric nanofibrous scaffold: A potential scaffold for soft tissue engineering.

With regard to flexibility and strength properties requirements of soft biological tissue, elastomeric materials could be more beneficial in soft tissue engineering applications. The present work investigates the use of an elastic polymer, (polycaprolactone fumarate [PCLF]), for fabricating an electrospun scaffold. PCLF with number-average molecular weight of 13,284 g/mol was synthetized, electrospun PCLF:polycaprolactone (PCL) (70:30) nanofibrous scaffolds were fabricated and a novel strategy (in situ photo-crosslinking along with wet electrospinning) was applied for crosslinking of PCLF in the structure of PCLF:PCL nanofibers was presented. Sol fraction results, Fourier-transform infrared spectroscopy, and mechanical tests confirmed occurrence of crosslinking reaction. Strain at break and Young's modulus of crosslinked PCLF:PCL nanofibers fabricated was found to be 114.5 ± 3.9% and 0.6 ± 0.1 MPa, respectively, and dynamic mechanical analysis results revealed elasticity of nanofibers. MTS assay showed biocompatibility of PCLF:PCL (70:30) nanofibrous scaffolds. Our overall results showed that electrospun PCLF:PCL nanofibrous scaffold could be considered as a candidate for further in vitro and in vivo experiments and its application for engineering of soft tissues subjected to in vivo cyclic mechanical stresses. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2371-2383, 2018.

Fabrication and characterization of two-layered nanofibrous membrane for guided bone and tissue regeneration application.

Membranes used in dentistry act as a barrier to prevent invasion of intruder cells to defected area and obtains spaces that are to be subsequently filled with new bone and provide required bone volume for implant therapy when there is insufficient volume of healthy bone at implant site. In this study a two-layered bioactive membrane were fabricated by electrospinning whereas one layer provides guided bone regeneration (GBR) and fabricated using poly glycerol sebacate (PGS)/polycaprolactone (PCL) and Beta tri-calcium phosphate (ß-TCP) (5, 10 and 15%) and another one containing PCL/PGS and chitosan acts as guided tissue regeneration (GTR). The morphology, chemical, physical and mechanical characterizations of the membranes were studied using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), tensile testing, then biodegradability and bioactivity properties were evaluated. In vitro cell culture study was also carried out to investigate proliferation and mineralization of cells on different membranes. Transmission electron microscope (TEM) and SEM results indicated agglomeration of ß-TCP nanoparticles in the structure of nanofibers containing 15% ß-TCP. Moreover by addition of ß-TCP from 5% to 15%, contact angle decreased due to hydrophilicity of nanoparticles and bioactivity was found to increase. Mechanical properties of the membrane increased by incorporation of 5% and 10% of ß-TCP in the structure of nanofibers, while addition of 15% of ß-TCP was found to deteriorate mechanical properties of nanofibers. Although the presence of 5% and 10% of nanoparticles in the nanofibers increased proliferation of cells on GBR layer, cell proliferation was observed to decrease by addition of 15% ß-TCP in the structure of nanofibers which is likely due to agglomeration of nanoparticles in the nanofiber structure. Our overall results revealed PCL/PGS containing 10% ß-TCP could be selected as the optimum GBR membrane in view point of physical and mechanical properties along with cell behavior. PCL/PGS nanofibers containing 10% ß-TCP were electrospun on the GTR layer for fabrication of final membrane. Addition of chitosan in the structure of PCL/PGS nanofibers was found to decrease fiber diameter, contact angle and porosity which are favorable for GTR layer. Two-layered dental membrane fabricated in this study can serve as a suitable substrate for application in dentistry as it provides appropriate osteoconductivity and flexibility along with barrier properties.

Synthesis of polyester urethane urea and fabrication of elastomeric nanofibrous scaffolds for myocardial regeneration.

Fabrication of bioactive scaffolds is one of the most promising strategies to reconstruct the infarcted myocardium. In this study, we synthesized polyester urethane urea (PEUU), further blended it with gelatin and fabricated PEUU/G nanofibrous scaffolds. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and X-ray diffraction were used for the characterization of the synthesized PEUU and properties of nanofibrous scaffolds were evaluated using scanning electron microscopy (SEM), ATR-FTIR, contact angle measurement, biodegradation test, tensile strength analysis and dynamic mechanical analysis (DMA). In vitro biocompatibility studies were performed using cardiomyocytes. DMA analysis showed that the scaffolds could be reshaped with cyclic deformations and might remain stable in the frequencies of the physiological activity of the heart. On the whole, our study suggests that aligned PEUU/G 70:30 nanofibrous scaffolds meet the required specifications for cardiac tissue engineering and could be used as a promising construct for myocardial regeneration.

Structural properties of scaffolds: Crucial parameters towards stem cells differentiation.

Tissue engineering is a multidisciplinary field that applies the principles of engineering and life-sciences for regeneration of damaged tissues. Stem cells have attracted much interest in tissue engineering as a cell source due to their ability to proliferate in an undifferentiated state for prolonged time and capability of differentiating to different cell types after induction. Scaffolds play an important role in tissue engineering as a substrate that can mimic the native extracellular matrix and the properties of scaffolds have been shown to affect the cell behavior such as the cell attachment, proliferation and differentiation. Here, we focus on the recent reports that investigated the various aspects of scaffolds including the materials used for scaffold fabrication, surface modification of scaffolds, topography and mechanical properties of scaffolds towards stem cells differentiation effect. We will present a more detailed overview on the effect of mechanical properties of scaffolds on stem cells fate.

In vivo integration of poly(ε-caprolactone)/gelatin nanofibrous nerve guide seeded with teeth derived stem cells for peripheral nerve regeneration.

Artificial nanofiber nerve guides have gained huge interest in bridging nerve gaps and associated peripheral nerve regeneration due to its high surface area, flexibility and porous structure. In this study, electrospun poly (ε-caprolactone)/gelatin (PCL/Gel) nanofibrous mats were fabricated, rolled around a copper wire and fixed by medical grade adhesive to obtain a tubular shaped bio-graft, to bridge 10 mm sciatic nerve gap in in vivo rat models. Stem cells from human exfoliated deciduous tooth (SHED) were transplanted to the site of nerve injury through the nanofibrous nerve guides. In vivo experiments were performed in animal models after creating a sciatic nerve gap, such that the nerve gap was grafted using (i) nanofiber nerve guide (ii) nanofiber nerve guide seeded with SHED (iii) suturing, while an untreated nerve gap remained as the negative control. In vitro cell culture study was carried out for primary investigation of SHED-nanofiber interaction and its viability within the nerve guides after 2 and 16 weeks of implantation time. Walking track analysis, plantar test, electrophysiology and immunohistochemistry were performed to evaluate functional recovery during nerve regeneration. Vascularization was also investigated by hematoxilin/eosine (H&E) staining. Overall results showed that the SHED seeded on nanofibrous nerve guide could survive and promote axonal regeneration in rat sciatic nerves, whereby the biocompatible PCL/Gel nerve guide with cells can support axonal regeneration and could be a promising tissue engineered graft for peripheral nerve regeneration.

Advances in electrospun nanofibers for bone and cartilage regeneration.

Regeneration of bone and cartilage tissues has been an important issue for biological repair in the field of regenerative medicine. The rapidly emerging field of tissue engineering holds great promise for repair and generation of functional bone and cartilage substitutes with a combination of biomaterials, cells, drugs and growth factors. Scaffolds play a pivotal role in tissue engineering as they mimic the natural extracellular matrix (ECM) and play an important role in guiding cell adhesion and proliferation, and maintaining the normal phenotype of the tissues. The use of tissue-engineered grafts based on scaffolds has found to be a more effective method than conventional implantations of autograft, allograft, xenograft. In recent years much attention has been given to electrospinning as a feasible and versatile technique for fabrication of nanofibrous scaffolds, with large surface area to volume ratio, high porosity, mechanical properties and physical dimension similar to the ECM of natural tissues. Extensive research has been carried out for fabrication polymeric nanofibrous substrates with incorporation of hydroxyapatite nanoparticles or bone morphogenetic protein molecules for efficient tissue repair. Here we review on the literature of electrospun nanofibrous scaffolds, their modifications, and advances aimed towards the rapid regeneration of bone and cartilage.

Electrospun biocomposite nanofibrous patch for cardiac tissue engineering.

A bioengineered construct that matches the chemical, mechanical, biological properties and extracellular matrix morphology of native tissue could be suitable as a cardiac patch for supporting the heart after myocardial infarction. The potential of utilizing a composite nanofibrous scaffold of poly(dl-lactide-co-glycolide)/gelatin (PLGA/Gel) as a biomimetic cardiac patch is studied by culturing a population of cardiomyocyte containing cells on the electrospun scaffolds. The chemical characterization and mechanical properties of the electrospun PLGA and PLGA/Gel nanofibers were studied by Fourier transform infrared spectroscopy, scanning electron microscopy and tensile measurements. The biocompatibility of the scaffolds was also studied and the cardiomyocytes seeded on PLGA/Gel nanofibers were found to express the typical functional cardiac proteins such as alpha-actinin and troponin I, showing the easy integration of cardiomyocytes on PLGA/Gel scaffolds. Our studies strengthen the application of electrospun PLGA/Gel nanofibers as a bio-mechanical support for injured myocardium and as a potential substrate for induction of endogenous cardiomyocyte proliferation, ultimately reducing the cardiac dysfunction and improving cardiac remodeling.

Electrospun conducting polymer nanofibers and electrical stimulation of nerve stem cells.

Tissue engineering of nerve grafts requires synergistic combination of scaffolds and techniques to promote and direct neurite outgrowth across the lesion for effective nerve regeneration. In this study, we fabricated a composite polymeric scaffold which is conductive in nature by electrospinning and further performed electrical stimulation of nerve stem cells seeded on the electrospun nanofibers. Poly-L-lactide (PLLA) was blended with polyaniline (PANi) at a ratio of 85:15 and electrospun to obtain PLLA/PANi nanofibers with fiber diameters of 195 ± 30 nm. The morphology, chemical and mechanical properties of the electrospun PLLA and PLLA/PANi scaffolds were carried out by scanning electron microscopy (SEM), X-ray photo electron spectroscopy (XPS) and tensile instrument. The electrospun PLLA/PANi fibers showed a conductance of 3 × 10⁻9 S by two-point probe measurement. In vitro electrical stimulation of the nerve stem cells cultured on PLLA/PANi scaffolds applied with an electric field of 100 mV/mm for a period of 60 min resulted in extended neurite outgrowth compared to the cells grown on non-stimulated scaffolds. Our studies further strengthen the implication of electrical stimulation of nerve stem cells on conducting polymeric scaffolds towards neurite elongation that could be effective for nerve tissue regeneration.

Electrospun composite nanofibers for tissue regeneration.

Nanotechnology assists in the development of biocomposite nanofibrous scaffolds that can react positively to changes in the immediate cellular environment and stimulate specific regenerative events at molecular level to generate healthy tissues. Recently, electrospinning has gained huge momentum with greater accessibility of fabrication of composite, controlled and oriented nanofibers with sufficient porosity required for effective tissue regeneration. Current developments include the fabrication of nanofibrous scaffolds which can provide chemical, mechanical and biological signals to respond to the environmental stimuli. These nanofibers are fabricated by simple coating, blending of polymers/bioactive molecules or by surface modification methods. For obtaining optimized surface functionality, with specially designed architectures for the nanofibers (multi-layered, core-shell, aligned), electrospinning process has been modified and simultaneous 'electrospin-electrospraying' process is one of the most lately introduced technique in this perspective. Properties such as porosity, biodegradation and mechanical properties of composite electrospun nanofibers along with their utilization for nerve, cardiac, bone, skin, vascular and cartilage tissue engineering are discussed in this review. In order to locally deliver electrical stimulus and provide a physical template for cell proliferations, and to gain an external control on the level and duration of stimulation, electrically conducting polymeric nanofibers are also fabricated by electrospinning. Electrospun polypyrrole (PPy) and polyaniline (PAN) based scaffolds are the most extensively studied composite substrates for nerve and cardiac tissue engineering with or without electrical stimulations, and are discussed here. However, the major focus of ongoing and future research in regenerative medicine is to effectively exploit the pluripotent potential of Mesenchymal Stem Cell (MSC) differentiation on composite nanofibrous scaffolds for repair of organs.