Fabrication Of Nanofibrous Scaffolds Research Articles

Nanoscience and nanotechnology in fabrication of scaffolds for tissue regeneration

Nanofibers have attracted great research attention owing to their unique physicochemical characteristics and broad implementation potential. These one dimensional nanostructures are being increasingly applied in biomedical fields such as manufacturing the scaffolding materials for regenerate new tissues owing to their great surface area/to/volume ratio, high porosity by interrelated pore configuration and the suitable surface structure for cell attachment, proliferation, growth, adhesion, viability and differentiation. Nanofibrous scaffolds with porous construction can mimic the extra cellular matrix structure in providing the suitable area for cells in their microenvironment. Fabrication of nanofibrous scaffolds for cell cultivating is an important process for tissue engineering method. After that, implanting the scaffold―cell matrix in human body is a main stage for tissue regeneration. This review will consider important notes about tissue regeneration process briefly, and the novel explorations in manufacturing the nanostructure scaffolds will be reported.

Electrospun Nanofibers for Wound Dressing and Tissue Engineering Applications

Electrospinning has received tremendous attention in the fabrication of nanofibrous scaffolds over recent years and employed in different biomedical applications because of their biomimetic nature. Especially, the electrospun nanofibers exhibit several beneficial features including natural extracellular matrix (ECM), interconnected pores, large surface area, ease of functionalization and mechanical performance that holds huge importance in influencing the cell adhesion, differentiation and proliferation behaviour. To date, acknowledging the wide range of beneficial features, the electrospun nanofibers have been used in wound dressing and tissue engineering applications. This review summarizes various efforts have been made in these areas with several representative examples indicating use of various materials and approaches. Further the concerns for future direction regard to clinical phase transfer has been discussed.

Cover Image, Volume 12, Issue 4

AbstractThe cover image is based on the Advanced Review 2D and 3D electrospinning technologies for the fabrication of nanofibrous scaffolds for skin tissue engineering: A review, by Antonios Keirouz, Michael Chung, Jaehoon Kwon, Giuseppino Fortunato and Norbert Radacsi. https://doi.org/10.1002/wnan.1626. image

Fabrication and Characterization of Fe(III) Metal-organic Frameworks Incorporating Polycaprolactone Nanofibers: Potential Scaffolds for Tissue Engineering

Fabrication of nanofibrous scaffolds of biodegradable polymers provides a great premise for several biological applications. In this study, nanofibrous polycaprolactone (PCL) mats incorporating Fe-MOF (PCL/x%Fe-MOF, x=5, 10, 20) were fabricated by electrospinning technique. The Fe-MOFs were separately synthesized by the hydrothermal method and then were added to PCL solution for preparation of nanofibrous composites. The presence of Fe-MOF in the fibers was demonstrated by various methods including FT-IR (Fourier-transform infrared), PXRD (powder X-ray diffraction), EDS (energy dispersive X-ray spectroscopy) mapping, SEM (scanning electron microscope), and TEM (transmission electron microscope). In the FT-IR spectra of the nanocomposites, the characteristic bands for the pure PCL and Fe-MOF showed no significant change in their positions, suggesting a weak chemical interaction with each other, although they physically mixed uniformly. Nanofibrous structure of the as-prepared nanocomposites was confirmed by SEM and TEM images. The diameter of PCL nanofibers was measured to be 369 nm. Biological investigations indicated that the experimented scaffolds including PCL/5%Fe-MOF and PCL/10%Fe-MOF nanofibrous scaffolds provided appropriate surface and mechanical properties such as cellular biocompatibility, high porosity, chemical stability, and optimum fiber diameter for cell adhesion, viability, and proliferation compared with PCL and PCL/20%Fe-MOF nanocomposites. Indeed, our results demonstrated that percent of Fe-MOF in the composites played a significant role in cell attachment and viability. Also, according to the implantation studies, up to at least 4 weeks, none of the animals showed any inflammatory response. Totally, we can be claimed that the modified electrospun scaffolds have been developed for tissue engineering applications.

2D and 3D electrospinning technologies for the fabrication of nanofibrous scaffolds for skin tissue engineering: A review.

This review provides insights into the current advancements in the field of electrospinning, focusing on its applications for skin tissue engineering. Furthermore, it reports the evolvement and present challenges of advanced skin substitute product development and explores the recent contributions in 2D and 3D scaffolding, focusing on natural, synthetic, and composite nanomaterials. In the past decades, nanotechnology has arisen as a fascinating discipline that has influenced every aspect of science, engineering, and medicine. Electrospinning is a versatile fabrication method that allows researchers to elicit and explore many of the current challenges faced by tissue engineering and regenerative medicine. In skin tissue engineering, electrospun nanofibers are particularly attractive due to their refined morphology, processing flexibility-that allows for the formation of unique materials and structures, and its extracellular matrix-like biomimetic architecture. These allow for electrospun nanofibers to promote improved re-epithelization and neo-tissue formation of wounds. Advancements in the use of portable electrospinning equipment and the employment of electrospinning for transdermal drug delivery and melanoma treatment are additionally explored. Present trends and issues are critically discussed based on recently published patents, clinical trials, and in vivo studies. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

Fabrication of Nanofibrous Scaffold Grafted with Gelatin Functionalized Polystyrene Microspheres for Manifesting Nanomechanical Cues of Stretch Stimulated Fibroblast

Cells sense mechanical cues in their microenvironments and effectively transduce them into intracellular signaling events, which subsequently orchestrate adaptive changes in cells cytoskeletal components and other adhesion proteins. Thus far, although diverse nanostructured scaffold systems have been utilized for evaluating such mechanical cues, most of them do not recapitulate the in vivo conditions (ECM matrix, 3D culture), which by themselves obscure natural cellular responses in the first place. To address this drawback, in the present work, a hybrid aligned nanofibrous scaffold grafted with gelatin functionalized polystyrene microspheres has been adapted for assessing fibroblast cells mechanobiology in response to mechanical stimulation by stretch cycles. In this work, with the help of a rationally designed hybrid scaffold, we present clear evidence of that fact that fibroblast cells when subjected to mechanical stress tend to manifest higher magnitude traction force on the underlying hybrid scaffold, which consequently introduces proportional distortion in orientation of aligned nanofibers scaffold as well as the polystyrene microspheres. A clear insight into sequestration of focal adhesion proteins and cellular cytoskeletal dynamics that actuate such changes was perceived and quantified by confocal microscopy, field emission-scanning electron microscopy, flow cytometer, and atomic force microscopy (peak force QNM). The mechanical stress induced alteration in regulation of genes associated with focal adhesion proteins and extracellular matrix proteins was also quantified by real-time polymerase chain reaction. In summary, the work presents a biologically relevant 4D hybrid scaffold and validates its implications for evaluation of cell mechanobiology.

Novel Blowspun Nanobioactive Glass Doped Polycaprolactone/Silk Fibroin Composite Nanofibrous Scaffold with Enhanced Osteogenic Property for Bone Tissue Engineering

Blowspinning provides an efficient and easier way of nanofibers preparation that mimics the structure of native extracellular matrix (ECM) and can be applied as scaffolds to regenerate bone tissue at the defect site. The present study reports fabrication of nanofibrous scaffold with novel polymeric combination using polycaprolactone (PCL) and silk fibroin (SF), doped with nanobioactive glass (nBS). The PCL/SF nanofibers of average diameter 570 nm were obtained by blowspinning technique, and BS nanoparticles of 80±20 nm were produced by sol-gel method followed by ball milling. On nBS doping, the resulting 3D composite matrix exhibited excellent surface property, 85–86 % porosity, 2.2 MPa mechanical strength and were effectively colonized by umbilical cord blood derived human mesenchymal stem cells (hMSCs). The nanofibrous-composite scaffolds (PCL/SF/nBS) were superior to PCL and PCL/SF scaffolds in facilitating cell attachment, metabolic activity and distribution. The PCL/SF/nBS scaffolds promoted osteogenic differentiation of hMSCs as evident by immunofluorescence of Runt-related transcription factor 2 (RUNX2) and osteoclacin (OCN) in cell ECM, and upregulation of alkaline phosphatase, RUNX2, OCN and osteopontin genes. Incorporation of nBS into the nanofibrous structure resulted in enhanced biomineralization, thereby improving osteogenic differentiation potential. Thus blowspun PCL/SF/nBS scaffolds were demonstrated to be suitable platform for bone tissue engineering applications.

Silk nanofibrous electrospun scaffold enhances differentiation of embryonic stem like cells derived from testis in to mature neuron.

The scaffolds accompanied with stem cells have great potential for applications in neural tissue engineering. Fabrication of nanofibrous scaffold similar to extracellular matrix is one of the applicable methods in neural tissue regeneration. The aim of this study was the fabrication of a silk nanofibrous scaffold as a microenvironment for neural guiding differentiation of embryonic stem like cells (ES Like cells) derived from testis toward neuron-like cells. ES Like derived from culturing of testicular cells in vitro, were seeded on silk scaffolds and induced to neuronal phenotype using 4-/4± RA technique following culturing the cells in the neurobasal medium supplemented with 20 ng/mL bFGF,10 ng/mL EGF, B27, and N2 for 8-12 days. The neural differentiation was confirmed via the evaluation of specific neural markers; Nestin, NF68, MAP2 and β tubulin using immunocytochemistry and real-time polymerase chain reaction. Our results showed that silk scaffold support the attachment and proliferation of ES Like cells. The expression of Nestin, NF68, Map2, and ß tubulin markers were higher in cells grown on silk scaffold in compare to monolayer group. This study suggests electrospun silk nanofibrous scaffold as an appropriate substrate for neural induction of stem cells that is applicable for repairmen of damaged neural tissues. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2662-2669, 2018.

Tolnaftate\u2013graphene composite-loaded nanoengineered electrospun scaffolds as efficient therapeutic dressing material for regimen of dermatomycosis

Graphene “The novel carbon nano-trope” tailors auspicious platform for designing antimicrobial regimen by virtue of its conspicuous molecular interaction with the microorganism. In this work, Tolnaftate (Tf), an antifungal drug, was mingled with Graphene nanoplatelets (Gn) to develop composite (Tf–Gn) via the wet chemical route, embedded in a biocompatible polymeric blend of Eudragit RL100/Eudragit RS100 (EuRL100/EuRS100) and subjected to electrospinning to obtain nonwoven nanoengineered scaffolds (nanofibers) for enhanced anti-dermatophytic virtue. Pursuing cluster of optimization experiments, 20% w/v EuRL100/EuRS 100 was found to be adequate for formation of smooth, defect-free, and regular fibers. Field emission electron microscopy (FESEM) acknowledged zestfully fabrication of smooth, shiny, nano-range, and mesh-like architecture, comprising distinct pockets within their structure. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC) conceded formation of the composite Tf–Gn, its physical compatibility with polymers, and improved thermal behavior. Exceptional swelling capacity, significant hydrophilicity, and immense drug entrapment efficiency were obtained of nanofibers fabricated from 3:1 ratio of EuRL100/EuRS100 polymers blend owing to relatively higher permeability which gratified essential benchmark for fabrication of nanofibrous scaffold to alleviate fungal infections caused by dermatophytes. In vitro drug release interpreted controlled liberation of Tf in dissolution media, following Korsmeyer–Peppas model kinetics, and suggested a diffusion-based mechanism. Microdilution broth method was performed for in vitro antifungal efficacy against extremely devastating dermatophytes, i.e., anthropophilic Trichophyton rubrum and zoophilic Microsporum canis, exhibited preeminent growth inhibition against T.rubrum and scanty for M.canis. Findings revealed the superior antifungal activity of Tf–Gn-loaded nanofibers as compared to Tf-loaded nanofibers and recommended potential dressing materials for an effective regimen of dermatomycosis.

Selectivity and sensitivity of molybdenum oxide-polycaprolactone nanofiber composites on skin cancer: Preliminary in-vitro and in-vivo implications

Cancer nanomedicine has emerged as a revolution in the last decade opening up promising strides for the cancer treatment. The major challenge in these therapeutic approaches resides in the failure of clinical trials owing to the immunological cancer microenvironment. Therefore, the success of next generation nanomedicine depends on tunable physicochemical nanomaterial design and corresponding clinical trials by integrating targeted delivery with mitigated toxicity. The present study deals with the fabrication of nanofibrous scaffold impregnated with molybdenum nanoparticles for targeted skin cancer therapeutics. Molybdenum oxide, a transitional metal oxide is gaining rapid importance due to its vital role in cellular and molecular metabolism. Polycaprolactone nanofibers were chosen as a matrix to localize the nanoparticles topically facilitating selective apoptosis of the tumor cells over the normal cells with mitigated side effects. The scaffold was designed to tailor the physicochemical, mechanical and biological suitability for skin cancer (melanoma and non melanoma). The designed scaffold was found to reduce more than 50% cell viability of the cancer cells selectively through apoptosis as confirmed using AO/PI staining and the probable mechanism could be attributed to the induction of mitochondria dependent apoptosis as observed by JC1 dye staining. In-vivo trials in zebra fish were found to reduce cancer progression by more than 30% in 14 days. The fabricated molybdenum trioxide nano constructs not only serve as tunable targeted systems but also open venues capable of ferrying chemotherapeutic drugs sparing normal cells alleviating the trauma due to side effects.

Tolnaftate-Loaded PolyacrylateElectrospun Nanofibers for an Impressive Regimen on Dermatophytosis

Dermatophytosis, topical fungal infection is the most common cause of skin bug in the world, generally underestimated and ignored. It is commonly caused by immensely mortifying and keratinophilic fungal eukaryotes which invade keratinized tissues and generate different tinea diseases in Mediterranean countries. We herein fabricated nanofibers/scaffolds embedded with thiocarbamate derivative topical antifungal tolnaftatefor the first time to target the complete elimination of dermatophyte at the site of infection. In this regard, variable combinations of biocompatible Eudragit grades (ERL100 and ERS100) were selected to provide better adhesion on the site of dermatophytosis, ample absorption of exudates during treatment, and customized controlled drug release. Surface topography analysis indicated that the fabricated nanofibers were regular and defect-free, comprising distinct pockets with nanoscaled diameters. Characterization and compatibility studies of tolnaftate, polymers, and their nanofibers were performed through ATR-FTIR, TGA, and PXRD. Remarkable hydrophilicity and an excellent swelling index were obtained from a 3:1 ratio of ERL100/ERS100 electrospun D3 nanofibers, which is an essential benchmark for the fabrication of nanofibrous scaffolds for alleviating dermatophytosis. In vitro drug release investigation revealed that a nonwoven nanomesh of nanofibers could control the rate of drug release for 8 h. A microdilution assay exhibited inhibition of more than 95% viable cells of Trichophyton rubrum for 96 h. However, Microsporum species rigidly restricted the effect of bioactive antifungal nanofibers and hence showed resistance. In vivo activity on Trichophyton rubrum infected Swiss albino mice revealed complete inhibition of fungal pathogens on successive applications of D3 nanofibers for 7 days. This investigation suggests potential uses of tolnaftate loaded polyacrylate nanofibers as dressing materials/scaffolds for effective management of dermatophytosis.

Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics

The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a–5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: 1T46) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the proliferation of cancerous cells. We anticipate that our results can provide better potential research in nanomaterial based cancer research.

Chitosan-poly(vinyl alcohol) nanofibers by free surface electrospinning for tissue engineering applications.

Deformities in tissues and organs can be treated by using tissue engineering approach offering the development of biologically functionalized scaffolds from a variety of polymer blends which mimic the extracellular matrix and allow adjusting the material properties to meet the defect architecture. In recent years, research interest has been shown towards the development of chitosan (CS) based biomaterials for tissue engineering applications, because of its minimal foreign body reactions, intrinsic antibacterial property, biocompatibility, biodegradability and ability to be molded into various geometries and forms thereby making it suitable for cell ingrowth and conduction. The present work involves the fabrication of nanofibrous scaffold from CS and poly(vinyl alcohol) blends by free-surface electrospinning method. The morphology and functional characteristics of the developed scaffolds were assessed by field emission scanning electron microscopy and fourier transformed infra-red spectra analysis. The morphological analysis showed the average fiber diameter was 269 nm and thickness of the mat was 200-300 µm. X-ray diffraction study confirmed the crystalline nature of the prepared scaffolds, whereas hydrophilic characteristic of the prepared scaffolds was confirmed by measured contact angle. The scaffolds possess an adequate biodegradable, swelling and mechanical property that is found desirable for tissue engineering applications. The cell study using umbilical cord blood-derived mesenchymal stem cells has confirmed the in vitro biocompatibility and cell supportive property of the scaffold thereby depicting their potentiality for future clinical applications.

Electrospun Scaffolds for Corneal Tissue Engineering: A Review.

Corneal diseases constitute the second leading cause of vision loss and affect more than 10 million people globally. As there is a severe shortage of fresh donated corneas and an unknown risk of immune rejection with traditional heterografts, it is very important and urgent to construct a corneal equivalent to replace pathologic corneal tissue. Corneal tissue engineering has emerged as a practical strategy to develop corneal tissue substitutes, and the design of a scaffold with mechanical properties and transparency similar to that of natural cornea is paramount for the regeneration of corneal tissues. Nanofibrous scaffolds produced by electrospinning have high surface area–to-volume ratios and porosity that simulate the structure of protein fibers in native extra cellular matrix (ECM). The versatilities of electrospinning of polymer components, fiber structures, and functionalization have made the fabrication of nanofibrous scaffolds with suitable mechanical strength, transparency and biological properties for corneal tissue engineering feasible. In this paper, we review the recent developments of electrospun scaffolds for engineering corneal tissues, mainly including electrospun materials (single and blended polymers), fiber structures (isotropic or anisotropic), functionalization (improved mechanical properties and transparency), applications (corneal cell survival, maintenance of phenotype and formation of corneal tissue) and future development perspectives.

Tumor tissue growth within upper and lower, nanofibrous scaffolding constraints

Event Abstract Back to Event Tumor tissue growth within upper and lower, nanofibrous scaffolding constraints Kenneth Gan1, Jin Zou1 and Hongjun Wang1 1 Stevens Institute of Technology, Biomedical Engineering, Chemistry and Biological Sciences, United States Introduction: Breast cancer is the second most common cancer and accounts for nearly 40,000 deaths each year making it one of the most prominent and detrimental diseases amongst the adult female population. Nevertheless, a viable treatment regimen for combating cancerous tissues in vivo remains a sought after discovery within the biomedical field. Further, the development of three-dimensional (3D) tissue models could facilitate the personalization of patients’ treatment regimens. This study proposed the use of electrospun nanofiber meshes to support and confine the growth of metastatic breast cancer cells within upper and lower nanofibrous boundaries. Coupled with the rapid proliferation tendencies of this cell line, the use of an elastic spinning solution (composed of polycaprolactone and collagen) enables the cells to proliferate within the interior lumen. As the cells fill the compartment, the force imposed on the boundary scaffolds will stretch the polymer and allow the cells to develop a 3D thickness of approximately 100µm. Materials and Methods: Fabrication of nanofibrous scaffold A high voltage driven electrospinning setup was used to collect a dense layer of polycaprolactone (PCL) and collagen (PCL:collagen=3:1) nanofibers on a metal ring. Breast cancer cells (MDA-MB-231) were seeded onto the fibers with 9,000 cells per sample. After attachment, the top layer was spun in a similar manner such that pores enabled nutrient perfusion without cell migration. Cell culture analysis: After culturing for seven days, the cultured constructs were fixed and processed for histological analysis (i.e. hematoxylin and eosin staining). The stained cross-sections were examined under a bright field microscope and images were captured. Results and Discussion: In order to distinguish between 2D and 3D cultures, the first observation that was made involved cellular morphologies. MDA-MB-231 cells in 2D culture spread out and exhibit a pointed star shape; however, those of a 3D culture are ellipsoidal with much larger thicknesses (10-30µm). The histological staining results confirmed that cell morphologies within both samples matched the expected 3D shape (Fig. 1+2). In the case of the first sample, the linearity implied that it was excised from the tissue much cleaner than the second sample was. This produced a more uniform cell distribution with diameters ranging from 15-30µm (when measuring the longest diameter). Likewise, those in the second sample ranged from 15-35µm, both of which were within the expected diameter range for a 3D culture. The maximum tissue thicknesses recorded for the first and second samples were 84µm and 105µm, respectively. Conclusion: Not only did these results confirm the feasibility of the concept, but they also implied that the samples were not too thick to prevent the interior cells from remaining healthy. This was evidenced by the uniform cell morphologies observed from the top to bottom layers. Although this preliminary analysis was effective in demonstrating a perceived concept, future work would incorporate toxicity analyses to compare our model with existing 2D and 3D culturing mechanisms. Keywords: Cell Adhesion, 3D scaffold, in vivo tissue engineering Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Synthetic scaffolds as extracellular matrices Citation: Gan K, Zou J and Wang H (2016). Tumor tissue growth within upper and lower, nanofibrous scaffolding constraints. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.03052 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kenneth Gan Jin Zou Hongjun Wang Google Kenneth Gan Jin Zou Hongjun Wang Google Scholar Kenneth Gan Jin Zou Hongjun Wang PubMed Kenneth Gan Jin Zou Hongjun Wang Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Synthesis of functional polyester for fabrication of nano-fibrous scaffolds and its effect on PC12 cells

An ideal scaffold should mimic the advantageous characteristics of a natural extracellular matrix for cell attachment, proliferation, and differentiation. In this study, well-defined block copolymer with functional groups was synthesized. The structure of the block copolymer was characterized by nuclear magnetic resonance, gel permeation chromatography, and differential scanning calorimetry. Thermally induced phase separation was employed to fabricate nano-fibrous scaffolds based on the synthesized block copolymer. The scaffold, with fiber diameter ranging from 400 to 500 nm, was fabricated for in vitro culture of PC12 cells. The carboxyl groups on the side chain resulted in increased hydrophilicity of nano-fibrous scaffolds and enhanced cell proliferation. In addition, this scaffold structure was beneficial in directing the growth of regenerating axons in nerve tissue engineering. Results of 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay and scanning electron microscopy confirmed that the nano-fibrous scaffolds with functional groups were suitable for PC12 cells growth. Moreover, the carboxyl groups were suitable for coupling with biological signals. Thus, the nano-fibrous scaffolds have potential applications in tissue engineering.

Recent Advances in Electrospun Nanofibrous Scaffolds for Cardiac Tissue Engineering

Cardiovascular diseases remain the leading cause of human mortality worldwide. Some severe symptoms, including myocardial infarction and heart failure, are difficult to heal spontaneously or under systematic treatment due to the limited regenerative capacity of the native myocardium. Cardiac tissue engineering has emerged as a practical strategy to culture functional cardiac tissues and relieve the disorder in myocardium when implanted. In cardiac tissue engineering, the design of a scaffold is closely relevant to the function of the regenerated cardiac tissues. Nanofibrous materials fabricated by electrospinning have been developed as desirable scaffolds for tissue engineering applications because of the biomimicking structure of protein fibers in native extra cellular matrix. The versatilities of electrospinning on the polymer component, the fiber structure, and the functionalization with bioactive molecules have made the fabrication of nanofibrous scaffolds with suitable mechanical strength and biological properties for cardiac tissue engineering feasible. Here, an overview of recent advances in various electrospun scaffolds for engineering cardiac tissues, including the design of advanced electrospun scaffolds and the performance of the scaffolds in functional cardiac tissue regeneration, is provided with the aim to offer guidance in the innovation of novel electrospun scaffolds and methods for improving their potential for cardiac tissue engineering applications.

Fabrication and Characterization of Electrospun Polycaprolactone Blended with Chitosan-Gelatin Complex Nanofibrous Mats

Design and fabrication of nanofibrous scaffolds should mimic the native extracellular matrix. This study is aimed at investigating electrospinning of polycaprolactone (PCL) blended with chitosan-gelatin complex. The morphologies were observed from scanning electron microscope. As-spun blended mats had thinner fibers than pure PCL. X-ray diffraction was used to analyze the degree of crystallinity. The intensity at two peaks at 2θof 21° and 23.5° gradually decreased with the percentage of chitosan-gelatin complex increasing. Moreover, incorporation of the complex could obviously improve the hydrophilicity of as-spun blended mats. Mechanical properties of as-spun nanofibrous mats were also tested. The elongation at break of fibrous mats increased with the PCL content increasing and the ultimate tensile strength varied with different weight ratios. The as-spun mats had higher tensile strength when the weight ratio of PCL to CS-Gel was 75/25 compared to pure PCL. Both as-spun PCL scaffolds and PCL/CS-Gel scaffolds supported the proliferation of porcine iliac endothelial cells, and PCL/CS-Gel had better cell viability than pure PCL. Therefore, electrospun PCL/Chitosan-gelatin nanofibrous mats with weight ratio of 75/25 have better hydrophilicity mechanical properties, and cell proliferation and thus would be a promising candidate for tissue engineering scaffolds.

Electrospun Gelatin Constructs with Tunable Fiber Orientation Promote Directed Angiogenesis

The field of therapeutic angiogenesis has been predominantly concentrated in modalities that incorporate pro-angiogenic growth factors and/or cells within polymeric constructs that are implanted into the ischemic region. There is growing evidence that construct architecture can significantly affect growth factor activity, cellular viability and differentiation potential. Electrospinning is an attractive but simple scaffold fabrication technique that offers several advantages over traditional fabrication approaches to prepare highly organized structures for therapeutic angiogenesis applications. We recently described the fabrication of nanofibrous scaffolds with aligned fiber orientation that directed cell migration and orientation (i.e.human umbilical vein endothelial cells). Herein we demonstrate the ability of bFGF containing nanofibrous gelatin B scaffolds with controlled fiber orientation to promote capillary formation in vivo. Aligned scaffolds loaded with bFGF induced the highest levels of reperfusion (73% increased in LDPI ratios by day 21 post ischemia induction) in comparison to all other groups including scaffolds with random fiber orientation. Furthermore, the newly formed vasculature, assessed by confocal microscopy, had a parallel alignment along the axis of the scaffold’s fibers. In contrast, no vessel directionality was observed in the animals treated with scaffolds with random fiber orientation in the presence or absence of bFGF.

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.