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Progress in Electrospun Fibers for Manipulating Cell Behaviors

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Abstract

The manipulation of cell behaviors is essential to maintaining cell functions, which plays a critical role in repairing and regenerating damaged tissue. To this end, a rich variety of tissue-engineered scaffolds have been designed and fabricated to serve as matrix for supporting cell growth and functionalization. Among others, scaffolds made of electrospun fibers showed great potential in regulating cell behaviors, mainly owing to their capability of replicating the dimension, composition, and function of the natural extracellular matrix. In particular, electrospun fibers provided both topological cues and biofunctions simply by adjusting the electrospinning parameters and/or post-treatment. In this review, we summarized the most recent applications and advances in electrospun nanofibers for manipulating cell behaviors. First, the engineering of the secondary structures of individual fibers and the construction of two-dimensional nanofiber mats and nanofiber-based, three-dimensional scaffolds were introduced. Then, the functionalization strategies, such as endowing the fibers with bioactive, physical, and chemical cues, were explored. Finally, the typical applications of electrospun fibers in controlling cell behaviors (i.e., cell adhesion and proliferation, infiltration, migration, neurite outgrowth, stem cell differentiation, and cancer cell capture and killing) were demonstrated. Taken together, this review will provide valuable information to the specific design of nanofiber-based scaffolds and extend their use in controlling cell behaviors for the purpose of tissue repair and regeneration.

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Fig. 1
Fig. 2

Reproduced with permission from ref [49], Copyright 2008, Elsevier. C Scanning electron microscopy (SEM) images showing the morphology of PS fibers electrospun at the concentration of 15% with (i) dichloromethane, (ii) tetrahydrofuran, (iii) N,N-dimethylformamide, and (iv) cyclohexanone as the solvent, respectively. The insert in (iii) shows the PS fibers with a rough surface. Reproduced with permission from ref [53], Copyright 2015, Springer Nature. D The preparation process of core–shell or island-shaped PLA/CS nanofibers. SEM images showing the generation of CS islands on PLA fibers at 35 °C, 50 °C, and 60 °C. Reproduced with permission from ref [35], Copyright 2017, American Chemical Society. E Illustration of three possible mechanisms for generating the grooves on fibers

Fig. 3

Reproduced with permission from ref [41], Copyright 2021, MDPI. B Schematic illustration showing the influence of nanofiber-based mesh on the growth behavior of cells. C SEM images and diameter distribution of electrospun microfibers from PS with tetrahydrofuran as the solvent at different concentrations of 20.0 wt%, 22.5 wt%, and 25.0 wt%, respectively. Reproduced with permission from ref [70], Copyright 2020, MDPI. D Schematic illustration of circular and linear gradients of bioactive factors or electrosprayed nano-/microparticles on uniaxially and radially aligned fibers, respectively

Fig. 4

Reproduced with permission from ref [97], Copyright 2018, Elsevier. D Schematic illustration of the typical process of aerogel preparation. Reproduced with permission from ref [108], Copyright 2019, Royal Society. E 3D printing of inks containing short fibers: (i) SEM image of electrospun gelatin/ PLGA fibers; (ii) photograph of the powder of fibers; (iii) photograph showing the injectability of the fiber-contained inks; (iv) photograph showing the 3D-printed scaffolds. Reproduced with permission from ref [115], Copyright 2019, Elsevier

Fig. 5

Reproduced with permission from ref [128], Copyright 2020, Elsevier. B Schematic illustration showing the fabrication of electrospun SF/PCL nanofibers followed by incubation with ECM. The as-obtained membrane was named NaRE. (i) SEM image of the NaRE membrane. (ii) Magnified SEM image of the region labeled by the white box in (i). Red and yellow arrows indicate SF/PCL nanofibers and ECM, respectively. (iii) SEM image of the cross section of the NaRE membrane. Reproduced with permission from ref [133], Copyright 2022, IOP Publishing. C Schematic diagram of the preparation of the PCL/polypeptide nanofibers and their use for antibacterial therapy against Escherichia coli and Staphylococcus aureus. Reproduced with permission from ref [131], Copyright 2018, Elsevier. D SEM images showing the morphology of nanofibers with graded coating of mineral contents aligned the aligned-to-random fibers. E The corresponding fluorescent microphotographs showing the morphologies of TDSCs cultured on the different regions of nanofibers. Reproduced with permission from ref [143], Copyright 2022, Springer Nature

Fig. 6

Reproduced with permission from ref [150], Copyright 2018, Elsevier. C (i) Schematic illustration showing the cell culture device with electrical stimulation. The edges of nanofiber scaffolds were attached to steel rings, and electrical stimulation of 10, 50, or 100 mV was applied for 3 or 6 h using an electrochemical device. (ii) Fluorescent micrograph showing the axonal extension of PC12 cells after culturing on the SF scaffolds, Reproduced with permission [151], Copyright 2019, Elsevier. D Photographs, SEM, and atomic force microscopy images (the insets) showing the PPy-coated PLCL/SF nanofibers with increased PPy contents from (i) to (iv). Reproduced with permission from ref [153], Copyright 2016, Royal Society of Chemistry

Fig. 7

Reproduced with permission from ref [156], Copyright 2019, Elsevier. C (i, ii) Piezoelectric characterizations: (i) The displacement amplitude; (ii) Piezoresponse force microscopy results. Reproduced with permission from ref [161], Copyright 2017, Elsevier. D Tensile stress of the Ag-HAp@PCL nanofiber scaffolds with different Ag+ concentrations. E SEM images showing the HFB4 cells attached to the Ag-HAp@PCL nanofibers with different Ag+ concentrations at 3 days post cell culture. Reproduced with permission from ref [2], Copyright 2021, Elsevier

Fig. 8
Fig. 9
Fig. 10

Reproduced with permission from ref [165], Copyright 2019, Elsevier. B (i) Fluorescent micrographs and (ii) SEM images showing the growth of ECs on the HA/PLA and PLA microfibers, respectively, after 72-h seeding. The control group in (i) refers to the cell culture plate. (iii) The proliferation of ECs after culturing on the HA/PLA and PLA microfibers and TCP for 1, 3, and 5 days. Reproduced with permission from ref [175], Copyright 2021, Elsevier

Fig. 11

Reproduced with permission from ref [185], Copyright 2021, Elsevier

Fig. 12

Reproduced with permission from ref [192], Copyright 2022, IOP Publishing. C The migration of fibroblasts after culturing on the radially aligned PCL nanofibers coated with a density gradient of or uniform collagen nanoparticles and the blank nanofibers for 3 days: (i) fluorescent micrographs; (ii) cell numbers in the different migration zones; (iii) the migration distance. Reproduced with permission from ref [194], Copyright 2022, Wiley

Fig. 13

Reproduced with permission from ref [37], Copyright 2020, Wiley. D (i) Schematic illustration indicating the neurite outgrowth from PC12 cells after culturing on the tri-layered NGCs consisting of two layers of PCL nanofibers as the top and bottom layer, NGF@PCM microparticles sandwiched between two layers as a middle layer. When an 808-nm NIR laser irradiated the construct, NGF could be released from the sandwiched PCM particles. (ii, iii) Fluorescent micrographs of the typical neurite fields extending from the spheroids of PC12 cells after culturing on the NGCs for 7 days with the (ii) absence or (iii) presence of laser irradiation. Reproduced with permission from ref [140], Copyright 2018, Wiley

Fig. 14

Reproduced with permission from ref [198], Copyright 2016, American Chemical Society. C (i-vi at top panels) SEM images showing the morphological gradient of core–shell polyethylene glycol@PCL microfibrous scaffolds with various hollow core dimensions; (i-vi at bottom panels) Typical histology micrographs showing the osteogenic (alizarin red staining) and chondrogenic (alcian blue staining) differentiation of MSCs after culturing on the gradient scaffolds for 49 days. Reproduced with permission from ref [199], Copyright 2019, American Chemical Society. D Schematic illustration showing the PLGA nanofibers incorporated with GO and statistical analysis of osteocalcin secretion after culturing MSCs for 14 and 28 days with or without adding dexamethasone in the culture medium. PLGA was electrospun at a concentration of 15% or 18%, and GO was added at the same concentration of 1%. Reproduced with permission from ref [200], Copyright 2015, American Chemical Society. E SEM images of the nanofibers made of a blend of PLGA, collagen, and HAp with random, aligned, and latticed features. The corresponding micro-computed tomography images showing the 3D reconstruction of rat calvarias after implanting the different scaffolds into calvarial bone defects for 6 weeks. Red dotted circles indicate the defect areas. Reproduced with permission from ref [201], Copyright 2021, Elsevier

Fig. 15

Reproduced with permission from ref [202], Copyright 2018, John Wiley and Sons. B Kaplan–Meier curve showing freedom from local recurrence when treating lung cancer using cisplatin-loaded nanofiber mats and control groups (implantation of nanofibers unloaded with drugs plus intraperitoneal cisplatin, intraperitoneal cisplatin, and implantation of nanofibers unloaded with dugs plus intraperitoneal saline). Reproduced with permission from ref [203], Copyright 2016, Elsevier. C Photographs showing the tumor sites (i) before treatment, (ii) during treatment using the PCL/Fe3O4 nanofiber bandage by sticking it on the surface of a surgical dressing under the induction coils, and treated by (iii) five doses of hyperthermic cycles and every cycle lasting for 15 min; (iv) The recovery at 2 weeks post treatment. Reproduced with permission from ref [204], Copyright 2020, Wiley. D Schematic illustration of streptavidin-grafted PLGA nanofibers to isolate and capture the circulating tumor cells

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (32171322, 82001970), Natural Science Foundation of Shandong Province (ZR2021QC063, ZR2021YQ17), Young Elite Scientists Sponsorship Program by CAST (No. YESS20200097), State Key Laboratory for Modification of Chemical Fibers and Polymer Materials (KF2215), Qingdao Key Health Discipline Development Fund (2020-2022), Qingdao Clinical Research Center for Oral Diseases (22-3-7-lczx-7-nsh), and the Startup Funding of Qingdao University (T.W.). We also thank the "Advanced Biomaterials and Regenerative Medicine" Innovation Team supported by the Young-Talent Introduction and Cultivation Plan in the Universities of Shandong Province.

Funding

National Natural Science Foundation of China, 32171322, Tong Wu, 82001970, Tong Wu, Natural Science Foundation of Shandong Province, ZR2021QC063, Yuanfei Wang, ZR2021YQ17, Tong Wu, Young Elite Scientists Sponsorship Program by CAST, No. YESS20200097, Tong Wu, Startup Funding of Qingdao University, T.W., Tong Wu, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, KF2215, Tong Wu, Qingdao Key Health Discipline Development Fund, 2020-2022, Yuanfei Wang, Qingdao Clinical Research Center for Oral Diseases, 22-3-7-lczx-7-nsh, Yuanfei Wang.

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Author notes

  1. Yingnan Liu, Qingxia Guo, and Xiaopei Zhang contributed equally to this work.

Authors and Affiliations

  1. Institute of Neuroregeneration and Neurorehabilitation, Qingdao Medical College, Qingdao University, Qingdao, 266071, Shandong, China

    Yingnan Liu, Qingxia Guo, Xiaopei Zhang & Tong Wu

  2. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, 201620, China

    Xiumei Mo & Tong Wu

  3. Central Laboratory, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, 266001, Shandong, China

    Yuanfei Wang

  4. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China

    Xiumei Mo

  5. Shandong Key Laboratory of Medical and Health Textile Materials, Collaborative Innovation Center for Eco-textiles of Shandong Province and the Ministry of Education, College of Textiles & Clothing, Qingdao, 266071, Shandong, China

    Tong Wu

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  1. Yingnan Liu
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Correspondence to Yuanfei Wang or Tong Wu.

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Liu, Y., Guo, Q., Zhang, X. et al. Progress in Electrospun Fibers for Manipulating Cell Behaviors. Adv. Fiber Mater. 5, 1241–1272 (2023). https://doi.org/10.1007/s42765-023-00281-9

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