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3D electrospun nanofibrous scaffolds have been developed for cartilage regeneration, however, there is no consensus on the preferable method for biocompatible scaffolds that enhance regeneration and attenuate inflammation. We designed a 3D porous electrospun polylactic acid (PLA) @gelatin-based scaffold by a novel method. Chondroitin sulfate (CS), commonly used in clinical cartilage treatment, is capable of regulating cartilage formation and inhibiting inflammation. Thus we further functionalized the 3D scaffold by crosslinking of CS, assuming that CS-functionalized scaffold (CSS) would promote cartilage regeneration and modulate inflammation. We confirmed that CSS exhibits not only appropriate reversible compressibility and mechanical property, but also appropriate biocompatibility, allowing cell proliferation. In vitro, the potential of CSS for chondrogenic differentiation was improved compared to control and PLA@gelatin scaffold as chondrogenic markers Collagen2 and Aggrecan was significantly increased. Meanwhile, significant reduction in two crucial inflammatory factors (NO and PGE2) in CSS group demonstrated inflammation inhibition. In vivo, rabbit cartilage defects were created and CSS effectively promoted cartilage repair. Additionally, superior anti-inflammation effect of CSS was demonstrated by reduction in iNOS and PGES, enzymes producing NO and PGE2, respectively by immunohistology. Our results indicated the preferable property of CSS for cartilage regeneration and its potential in immunoregulation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Tissue scaffolds with three-dimensional (3D) nanofibrous biomimetic structures have attracted attention in the field of bone regeneration. In recent years, emerging strategies based on electrospinning technologies have facilitated the preparation of 3D nanofibrous scaffolds. Based on these developments, in this study, 3D scaffolds possessing both nanofibrous morphologies and interconnected pores were fabricated for their potential in bone tissue engineering. By combining homogenizing, freeze-drying, and thermal crosslinking techniques, nano-hydroxyapatite/PLLA/gelatin (nHA/PLA/GEL) 3D nanofibrous scaffolds were prepared using pre-fabricated electrospun nanofibers. Then, utilizing a polydopamine (pDA)-assisted coating strategy, bone morphogenetic protein-2 (BMP-2)-derived peptides were further immobilized onto the 3D scaffolds to obtain the resulting nano-hydroxyapatite/PLLA/gelatin-peptide (nHA/PLA/GEL-PEP) 3D nanofibrous scaffolds capable of sustained release. Bone mesenchymal stem cells (BMSCs) were cultured on the 3D nanofibrous scaffolds, then relative cell viability, alkaline phosphatase (ALP) activity, and gene expression assays were performed to study the effects of the scaffolds on cell growth and osteogenic differentiation in vitro. Furthermore, the ability of bone formation in vivo was evaluated using a rat cranial bone defect model. In vitro and in vivo results demonstrated that the 3D nanofibrous scaffolds incorporated with nHA and BMP-2 peptides exhibited favorable biocompatibility and osteoinductivity. Therefore, these nanofibrous scaffolds have excellent potential in bone regenerative medicine., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the study of hollow nerve guidance conduit (NGC), the dispersion of regenerated axons always confused researchers. To address this problem, filler-containing NGC was prepared, which showed better effect in the application of nerve tissue engineering. In this study, nanofiber sponges with abundant macropores, high porosity, and superior compressive strength were fabricated by electrospinning and freeze-drying. Poly(l-lactic acid-co-ε-caprolactone)/silk fibroin (PLCL/SF) nanofiber sponges were used as filler to prepare three-dimensional nanofiber sponges-containing (NS-containing) NGC. In order to study the effect of fillers for nerve regeneration, hollow NGC was set as control. In vitro cell viability studies indicated that the NS-containing NGC could enhance the proliferation of Schwann cells (SCs) due to the macroporous structure. The results of hematoxylin-eosin (HE) and immunofluorescence staining confirmed that SCs infiltrated into the nanofiber sponges. Subsequently, the NS-containing NGC was implanted in a rat sciatic nerve defect model to evaluate the effect in vivo. NS-containing NGC group performed better in nerve function recovery than hollow NGC group. In consideration of the walking track and triceps weight analysis, NS-containing NGC was close to the autograft group. In addition, histological and morphological analyses with HE and toluidine blue (TB) staining, and transmission electron microscope (TEM) were conducted. Better nerve regeneration was observed on NS-containing NGC group both quantitatively and qualitatively. Furthermore, the results of three indexes' immuno-histochemistry and two indexes' immunofluorescence all indicated good nerve regeneration of NS-containing NGC as well, compared with hollow NGC. The results demonstrated NS-containing NGC had great potential in the application of peripheral nerve repair.

Stent insertion and chemical agents of ethylene diamine tetraacetic acid and sodium cholate for dissolving common bile duct stone diseases through extra biliary tract infusion have been believed a relatively effective therapeutics for the clinical symptom. Core-shell nanofibers produced by co-axial electrospinning to deliver chemical drugs, biomacromolecules, genes and even cells have been reported for various advanced drug delivery system and tissue engineering applications. In the present study, poly (lactide-co-ɛ-caprolactone) (PLCL) core-shell nanofiber-coated film of stent, loaded with ethylene diamine tetraacetic acid and sodium cholate in core layer, was fabricated by co-axial electrospinning for treating gallstone disease. Image of laser scanning confocal microscopy and transmission electron microscopy demonstrated core-shell structure of drug-loaded nanofiber. Fourier transform infrared spectra and the thermogravimetric analysis proved ethylene diamine tetraacetic acid and sodium cholate to be successfully loaded in nanofibers. Morphology of nanofibers after a period of degradation still keeps good shape. Drugs can continuously release for around five days, which was proved significant effectiveness for dissolving gallstone. Besides, unobvious cytotoxicity was exhibited from MTT results and cell kept good morphology in vitro research. The present coated stent showed a bright prospect for dissolving the biliary stone., (© The Author(s) 2016.)

Electrospun nanofibers have been used for various biomedical applications. However, electrospinning commonly produces two-dimensional (2D) membranes, which limits the application of nanofibers for the 3D tissue engineering scaffold. In the present study, a porous 3D scaffold (3DS-1) based on electrospun gelatin/PLA nanofibers has been prepared for cartilage tissue regeneration. To further improve the repairing effect of cartilage, a modified scaffold (3DS-2) cross-linked with hyaluronic acid (HA) was also successfully fabricated. The nanofibrous structure, water absorption, and compressive mechanical properties of 3D scaffold were studied. Chondrocytes were cultured on 3D scaffold, and their viability and morphology were examined. 3D scaffolds were also subjected to an in vivo cartilage regeneration study on rabbits using an articular cartilage injury model. The results indicated that 3DS-1 and 3DS-2 exhibited superabsorbent property and excellent cytocompatibility. Both these scaffolds present elastic property in the wet state. An in vivo study showed that 3DS-2 could enhance the repair of cartilage. The present 3D nanofibrous scaffold (3DS-2) would be promising for cartilage tissue engineering application.

Fabrication of 3D scaffold to mimic the nanofibrous structure of the nature extracellular matrix (ECM) with appropriate mechanical properties and excellent biocompatibility, remain an important technical challenge in tissue engineering. The present study reports the strategy to fabricate a 3D nanofibrous scaffold with similar structure to collagen in ECM by combining electrospinning and freeze-drying technique. With the technique reported here, a nanofibrous structure scaffold with hydrophilic and superabsorbent properties can be readily prepared by Gelatin and Polylactic acid (PLA). In wet state the scaffold also shows a super-elastic property, which could bear a compressive strain as high as 80% and recovers its original shape afterwards. Moreover, after 6 days of culture, L-929 cells grow, proliferate and infiltrated into the scaffold. The results suggest that this 3D nanofibrous scaffold would be promising for varied field of tissue engineering application., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Restenosis caused by thrombopoiesis is one of the biggest hinders of endovascular stent-graft used in small-diameter vessels. Rapid endothelialization of the lumen of stent is a promising approach to prevent thrombosis. In this study, we aimed at loading heparin, a potent anticoagulants, and vascular endothelial growth factor (VEGF) into the core of poly(L-lactide-co-caprolactone) nanofiber via emulsion electrospinning. The nanofiber was covered on the stent and applied in the treatment of vascular diseases such as aneurysm. The morphologies of the emulsion electrospun nanofibers and core--shell structure were observed by scanning electron microscope and laser scanning confocal microscope. The release profiles of heparin and VEGF, degradation rate of nanofiber mats and cell proliferation in vitro were investigated. It was found that the release of both heparin and VEGF from the nanofiber lasted for more than 30 days without serious initial burst release. The degradation rate of nanofiber mats containing heparin and VEGF was faster than that of pure PLCL nanofiber mats. Moreover, the released VEGF could promote the proliferation of Pig iliac endothelial cells (PIECs) cultured on the nanofiber mat, which was of great benefit to stent endothelialization. The results of digital subtraction angiography (DSA) follow-up indicated the aneurysm was obliterated by separating the aneurysm dome from the blood circulation and the parent artery kept long-term patency. Results of the study demonstrated that the heparin and VEGF loaded nanofiber could provide an approach to fabricate covered stent-graft with properties of anticoagulation and induction of rapid endothelialization.

Silk fibroin (SF)/PEO nanofibers prepared by green electrospinning is safe, non-toxic and environment friendly, it is a potential drug delivery carrier for tissue engineering. In this study, a core-shell nanofibers named as Dex@SF/PEO were obtained by green electrospinning with SF/PEO as the shell and dexamethasone (Dex) in the core. The nanofiber morphology and core-shell structure were studied by Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). The Dex release behavior from the nanofibers was tested by High Performance liquid (HPLC) method. The protective effect of drug loaded nanofibers mats on Porcine hip artery endothelial cells (PIECs) against LPS-induced inflammatory damage were determined by MTT assay. TEM result showed the distinct core-shell structure of nanofibers. In vitro drug release studies demonstrated that dexamethasone can sustain release over 192 h and core-shell nanofibers showed more slow release of Dex compared with the blending electrospinning nanofibers. Anti-inflammatory activity in vitro showed that released Dex can reduce the PIECs inflammatory damage and apoptosis which induced by lipopolysaccharide (LPS). Dex@SF/PEO nanofibers are safe and non-toxic because of no harmful organic solvents used in the preparation, it is a promising environment friendly drug carrier for tissue engineering., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A novel electrospun nanoyarn scaffold, aimed to improve cell infiltration and vascularization, as well as guide cell behaviors by its biomimetic structure, was fabricated for tissue engineering. Electrospun nanofibers were deposited and twisted into yarns in a water vortex before collecting on a rotating mandrel to form a nanoyarn scaffold. Field emission-scanning electronic microscope (FE-SEM) images revealed that the scaffold, composed of aligned nanoyarns (24 micro m) which were composed of a bundle of nanofibers, created a porous structure which may be conducive to cellular infiltration. Thus, we hypothesized that the biomimetic nanoyarn will have a positive influence on cell proliferation and morphology. Pig iliac endothelial cells (PIECs) and MC3T3-E1 pre-osteoblastic cells cultured on the nanoyarn scaffolds showed significantly higher proliferation rates than that on traditional electrospun nanofiber scaffolds. Histological analysis demonstrated that cells infiltrate throughout the nanoyarn scaffolds over a 10-day period, however, no cell infiltration was observed on the nanofiber scaffolds. Moreover, confocal microscopy images indicated that both PIECs and MC3T3-E1 pre-osteoblastic cells cultured on the nanoyarn scaffolds exhibit an extremely elongated morphology compared to the flattened morphology when cells were cultured on electrospun nanofiber scaffolds or tissue culture plates. Furthermore, complex capillary-like structures were observed when PIECs cultured on the nanoyarn scaffold for 7 days, indicating that the nanoyarns provide templates and topographical cues for the assembly of PIECs and the promotion of a capillary network in vitro. In conclusion, the positive cellular interactions on the nanoyarn scaffold demonstrate potential application for use in tissue engineering.

Electrospinning is a versatile and convenient technology to generate nanofibers suitable for tissue engineering. However, the low production rate of traditional needle electrospinning hinders its applications. Needleless electrospinning is a potential strategy to promote the application of electrospun nanofiber in various fields. In this study, disc-electrospinning (one kind of needleless electrospinning) was conducted to produce poly(ε-caprolactone)/gelatin (PCL/GT) scaffolds of different structure, namely the nanoscale structure constructed by nanofiber and multiscale structure consisting of nanofiber and microfiber. It was found that, due to the inhomogeneity of PCL/GT solution, disc-electrospun PCL-GT scaffold presented multiscale structure with larger pores than that of the acid assisted one (PCL-GT-A). Scanning electron microscopy images indicated the PCL-GT scaffold was constructed by nanofibers and microfibers. Mouse fibroblasts and rat bone marrow stromal cells both showed higher proliferation rates on multiscale scaffold than nanoscale scaffolds. It was proposed that the nanofibers bridged between the microfibers enhanced cell adhesion and spreading, while the large pores on the three dimensional (3D) PCL-GT scaffold provide more effective space for cells to proliferate and migrate. However, the uniform nanofibers and densely packed structure in PCL-GT-A scaffold limited the cells on the surface. This study demonstrated the potential of disc-electrospun PCL-GT scaffold containing nanofiber and microfiber for 3D tissue regeneration. [ABSTRACT FROM AUTHOR]

An electrospun-aligned nanoyarn-reinforced nanofibrous scaffold (NRS) was developed for tendon tissue engineering to improve mechanical strength and cell infiltration. The novel scaffold composed of aligned nanoyarns and random nanofibers was fabricated via electrospinning using a two-collector system. The aim of the present study was to investigate three different types of electrospun scaffolds (random nanofibrous scaffold, aligned nanofibrous scaffold and NRS) based on silk fibroin (SF) and poly( l -lactide- co -caprolactone) blends. Morphological analysis demonstrated that the NRS composed of aligned nanoyarns and randomly distributed nanofibers formed a 3D microstructure with relatively large pore sizes and high porosity. Biocompatibility analysis revealed that bone marrow-derived mesenchymal stem cells exhibited a higher proliferation rate when cultured on the NRS compared with the other scaffolds. The mechanical testing results indicated that the tensile properties of the NRS were reinforced in the direction parallel to the nanoyarns and satisfied the mechanical requirements for tendon repair. In addition, cell infiltration was significantly enhanced on the NRS. In conclusion, with its improved porosity and appropriate mechanical properties, the developed NRS shows promise for tendon tissue engineering applications. [ABSTRACT FROM AUTHOR]

The development of a biomimetic surface which is able to promote endothelialization is fundamental in the research for blood vessel substitutes to overcome the formation of thrombi or hyperplasia. In the present work, the fabrication of acrylamide-terminated glycine-arginine-glycine-aspartic peptides (Ac-GRGD) modified poly(ester-urethane) urea (PEUU) nanofibrous mats via electrospinning technique followed by covalent immobilizing method for improving its endothelialization was successfully achieved. Series of PEUU based polymers including PEUU, PEUU with t-butoxycarbonyl group (PEUU-Boc), and PEUU-amino group (PEUU-NH 2 ) were synthesized by a two-step solution polymerization and a de-protection process. The PEUU-RGD as-prepared nanofibrous mat was characterized using different techniques, such as, scanning electron microscopy, solide-state 13 C CP-MAS nuclear magnetic resonance, and stress-strain test. In addition, to motivate cell adhesion and proliferation, PEUU nanofibers mat was immobilized by coupling of Ac-GRGD. The results present that incorporation of Ac-GRGD peptide improved the mechanical properties and does not have negative effect on the morphology and the structure of PEUU nanofibers. From cell viability and cell morphology results, the prepared PEUU-RGD nanofiber mats are cytocompatible. Interestingly, the immobilized PEUU-RGD nanofibers possess lower hemolysis rate and an improved inhibition of platelet adhesion. Overall, Ac-GRGD peptides immobilized PEUU nanofibrous mats may have a potential application for vascular tissue engineering. [ABSTRACT FROM AUTHOR]

Electrospinning has been widely used in fabrication of tissue engineering scaffolds. Currently, most of the electrospun nanofibers performed like a conventional two-dimensional (2D) membrane, which hindered their further applications. Moreover, the low production rate of the traditional needle-electrospinning (NE) also limited the commercialization. In this article, disc-electrospinning (DE) was utilized to fabricate a three-dimensional (3D) scaffold consisting of porous macro/nanoscale fibers. The morphology of the porous structure was investigated by scanning electron microscopy images, which showed irregular pores of nanoscale spreading on the surface of DE polycaprolactone (PCL) fibers. Protein adsorption assessment illustrated the porous structure could significantly enhance proteins pickup, which was 55% higher than that of solid fiber scaffolds. Fibroblasts were cultured on the scaffold. The results demonstrated that DE fiber scaffold could enhance initial cell attachment. In the 7 days of culture, fibroblasts grew faster on DE fiber scaffold in comparison with solid fiber, solvent cast (SC) film and TCP. Fibroblasts on DE fibers showed a stretched shape and integrated with the porous surface tightly. Cells were also found to migrate into the DE scaffold up to 800 μm. Results supported the use of DE PCL fibers as a 3D tissue engineering scaffold in soft tissue regeneration. [ABSTRACT FROM AUTHOR]