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A portable solution blow spinning device for minimally invasive surgery hemostasis
Chemical Engineering Journal 387 (2020) 124052
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A portable solution blow spinning device for minimally invasive surgery hemostasis
T
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Yuan Gaoa,1, Hong-Fei Xianga,b,1, Xiao-Xiong Wanga, , Kang Yana, Qi Liua, Xin Lia, ⁎ Rui-Qiang Liua, Miao Yua,c, Yun-Ze Longa, a
Collaborative Innovation Center for Nanomaterials & Devices, College of Physics, Qingdao University, Qingdao 266071, China Department of Spine Surgery, Affiliated Hospital of Qingdao University, Qingdao 266071, China c Department of Mechanical Engineering, Columbia University, New York, NY 10027, United States b
H I GH L IG H T S
solved the problems of electrospinning technology in minimally invasive surgery. • Successfully solution blow spinning device was proposed for the first time. • ATwoportable • applications have been proposed, namely in situ rapid wound dressing and minimally invasive surgical visceral hemostasis.
A R T I C LE I N FO
A B S T R A C T
Keywords: Solution blow spinning Minimally invasive surgery Portable device Hemostasis Laparoscopic
In situ fiber deposition technology has shown great excellence in visceral hemostasis. In recent years, minimally invasive surgery has been widely welcomed by patients because of its small trauma, light pain and rapid recovery. In the treatment of minimally invasive surgical wounds, fiber deposition has the advantages of fast, convenient, disassemble free and low toxicity. However, due to the conductive nature of the human body and narrow space in thoracic and abdominal cavity, the use of electrospinning technology to deposit fibers have high risk of short circuit and creepage. Such adverse effects, on the one hand, bring dangers to patients, and on the other hand, they will destroy equipment such as endoscopes. In this work, we used gas-blowing spinning instead of high-voltage electricity to guide fiber deposition, and completed liver hemostasis in a minimally invasive surgical environment. Pathological section analysis revealed that the surgery did not trigger an additional inflammatory response. It is worth mentioning that the gas blowing system used in this work can be a portable one. The high pressure gas source is changed from a conventional air pump to a commercially available compressed gas bottle (weight ~284 g, air pressure ~0.6 MPa). The gas source is greatly optimized and the volume is smaller. It is more convenient to carry, which makes the combination of hemostasis and other surgical items more convenient. This method is similar to the hemostatic membrane prepared by electrospinning technology, which can avoid the use of drainage tube, thus providing a cutting-edge form for minimally invasive surgery.
1. Introduction Nanofibers have been widely used in biomedical engineering [1–3], filtration [4–6], catalysis [7,8], energy [9–11], food engineering [12] and other fields due to their excellent properties. In situ nanofiber deposition technology can deposit nanofibers on the wound surface [13]. By forming a fiber membrane that is light, thin and adhering well to the wound, rapid and large-area hemostasis can be achieved, especially for soft tissue hemostasis such as viscera [14]. Compared with traditional
hemostasis methods such as electrocoagulation, fusion, etc., hemostatic surface obtained by nanofiber deposition is more reliable, having lower risk of secondary bleeding. It does not cause new damage to the tissue, and the toxicity is very low [15]. To give an example, electrospinning (ES) technology is a well-known method which can directly and continuously prepare nanofibers. Its principle is to stretch and refine polymer solution or melt by electric field force, and then obtain nanofibers [16,17]. By using portable or handheld electrospinning apparatus [18], the in situ electrospinning technique can deposit nanofibers
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Corresponding authors. E-mail addresses: [email protected] (X.-X. Wang), [email protected] (Y.-Z. Long). 1 These two authors contributed to this work equally. https://doi.org/10.1016/j.cej.2020.124052 Received 1 November 2019; Received in revised form 31 December 2019; Accepted 4 January 2020 Available online 09 January 2020 1385-8947/ © 2020 Elsevier B.V. All rights reserved.
Chemical Engineering Journal 387 (2020) 124052
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onto the wound surface using an electric field. Nanoscale fibers can greatly enhance the van der Waals interaction between the surface of the tissue and the fibers, thus producing good adhesion [19]. Due to the small pore size of these hydrophobic fibers, the surface tension is sufficient to prevent blood outflow. In addition, blood cells are difficult to pass through these fibers, and fibrin can be attached to the porous structure, so a thin layer of fiber can be used to complete the hemostasis [20]. The fibers itself is degradable, and because of the low deposition amount, the toxicity of the tissue is extremely light, so the hemostatic method has an absolute advantage over other method such as the smear method [21]. This technology provides a modern and efficient technique for visceral hemostasis, and even avoids the use of drainage tubes, thus greatly reducing the secondary damage to patients and leading to less pain. As a typical means of low pain surgery, minimally invasive surgery has been widely welcomed by patients because of its small trauma, light pain, and rapid recovery. However, unlike traditional open surgery, the manipulating space during minimally invasive surgery is narrow. Considering that the human body is electrically conductive, electric field deposition of nanofibers can easily lead to short circuit and discharge with human tissues. And because of the integration of a variety of surgical instruments and electronic devices around the endoscope portion of during minimally invasive surgery, high-voltage electrodes of several thousand volts can easily burn the equipment. Therefore, minimally invasive surgery requires an in-situ nanofiber deposition technology that does not use high-voltage electricity. As another typical nanofiber deposition technology, gas-blowing spinning can also assist in the deposition of nanofibers. The high-speed gas stream is used instead of the high-voltage electricity to blow out the polymer precursor, and the fiber is stretched to a very fine shape under the repeated stretching of the turbulent gas stream. When using a solution, this technique is called solution blow spinning (SBS) [22]. It is conceivable that this technology can replace the high-voltage electricity to complete the minimally invasive surgery and avoid the damage of the high-voltage electricity to the human body and equipment. In addition, the high-speed airflow can blow out the precursor faster, so that more fibers can be deposited in a shorter time than electrospinning [23], thereby completing the hemostasis faster. In this work, we use a small dust removing tank instead of a huge air compressor or cylinder, and use a special gas conduit to complete the solution blow spinning process, so the volume of SBS is greatly reduced, which is more conducive to the integration of the equipment onto a tiny cavity lens. Animal experiments were performed using a pig to simulate hemostasis after liver tumor removal under minimally invasive surgery. The results showed that this method has a good hemostasis effect and does not induce tissue inflammation. The high velocity airflow is concentrated at the nozzle and is quickly attenuated without damaging the tissue.
materials and corresponding solvents were weighed by an electronic balance, and then they were mixed and stirred on a magnetic stirrer. After the polymer material was completely dissolved, we used the obtained polymer solution to spin at room temperature. In addition, we used the rapid medical glue α-cyanoacrylate (made by Guangzhou Baiyun Medical Glue Co., Ltd.) for the hemostatic material. This material is composed of N-octyl-2-cyanoacrylate and medical grade polymethyl methacrylate (PMMA, an additive to increase viscosity). 2.2. Solution blow spinning device Fig. 1 is the schematic diagram of the solution blow spinning device which was designed by the authors. The device consists of four parts: a dust removing tank (made by Shanghai Zhantu Chemical Co., Ltd.), a plastic thin tube with inner diameter of 2.8 mm, a syringe and a special curved needle. The plastic thin tube was connected to the outlet of the dust removing tank, and the needle of the syringe and the plastic thin tube were designed to be coaxial. When the apparatus was used, the syringe was pushed to cause the polymer solution to flow out while the trigger of the dust removing tank was pulled, thereby causing the polymer solution to form fibers under the action of a high pressure gas stream. In order to obtain a good spinning effect, the distance between the needle and the collecting plate was controlled between 20 cm and 40 cm. 2.3. Characterization The fiber morphology of the polymer fibers obtained by the designed apparatus can be examined by scanning electron microscopy (SEM, TM-1000, Hitachi). PVP and PCL fibers was also examined by Fourier transform infrared spectroscopy (FTIR, Thermo Scientific Nicolet iN10). The solution jet were recorded by a high-speed digital video camera (FASTCAM Mini UX100, Photron). The average diameter and diameter distribution of the fibers were measured by the software Nano measure 1.2 (the number of fibers measured was 30). The experimental data were processed by the software Origin2018 to obtain histogram of spinning efficiency, histogram of fiber changes with solution concentration and distance. 3. Results and discussion 3.1. Performance of the portable SBS device Similar to electrospinning, solution blow spinning also have solution jet. For the motion of solution jet, Eroglu et al. [24] have done a series of studies and proposed a formula:
L/ d = 0.5We−0.4R e 0.6
(1)
We and R e are Weber number and Reynolds number, respectively. Their definitions are as follows: 2. Experimental 2.1. Materials
We = dρa ur 2/2σ
(2)
R e = dρl ul / μl
(3)
where L is the intact length; d is needle inner diameter; ρa is the gas density; ur is the relative velocity between the solution jet and gas; σ is the surface tension of solution; ρl , ul and μl are the density of the
Table 1 shows the materials used in our experiments to prepare polymer solutions (all chemicals and solvents were of analytical grade and used without further purification). A certain proportion of polymer Table 1 Polymer solution used in the experiment. Polymer
Details
Polyvinyl pyrrolidone, PVP Polycaprolactone, PCL Polymethyl methacrylate, PMMA Polyvinyl butyral, PVB
MW MW MW MW
= = = =
1 300 000 g mol−1, ACROS 100 000 g mol−1, ACROS 210 000 g mol−1, ACROS 90000–120000 g mol−1, ACROS
2
Solvent
Concentration
Anhydrous ethanol Acetone Dimethylformamide (DMF) Anhydrous ethanol
13 wt% 18 wt% 22 wt% 7, 10, 13 wt%
Chemical Engineering Journal 387 (2020) 124052
Y. Gao, et al.
Fig. 1. Schematic diagram of the portable solution blow spinning device. Fig. 2. (a) Solution jet image taken with a high-speed digital video camera at a parameter of 8000 frames per second. (b) Solution jet image taken with a highspeed digital video camera at a parameter of 20,000 frames per second. SEM images of polymer fibers: (c) PCL, (d) PMMA, (e) PVP, (f) PVB, which were produced by the designed portable solution blow spinning device.
solution, the velocity of the jet and the viscosity of the solution, respectively. Eroglu et al. [24] found that the intact length (L ) of the solution jet became shorter as We increased and became longer as R e increased. Therefore, the high pressure airflow can cause the solution jet to undergo unstable bending and swing. The solution jet produced by the designed device is shown in Fig. 2. It can be seen that the motion of solution jet is an unstable swing (the vivid details can be found in Videos S1 and S2). Therefore, the motion of solution jet conforms to the above theory. In order to verify the practicability of the device we designed, we used the device to spin PCL (18 wt%), PMMA (22 wt%), PVP (13 wt%), and PVB (10 wt%) into fibers. The distance between the spinning needle and collector was 30 cm. The SEM images of the fibers is shown in Fig. 2c-f. The average diameter of the fibers were 1.27 μm (PCL), 1.11 μm (PMMA), 2.21 μm (PVP) and 1.80 μm (PVB), and the fiber diameter distribution is relatively concentrated, indicating that the fiber thickness is uniform. Therefore, the device we designed was proven to be feasible. High spinning efficiency is one of the advantages of solution blow spinning. Therefore, the spinning efficiency of the portable SBS device and the conventional electrospinning device were compared. We recorded the maximum weight of the polymer solution consumed by the two devices in one minute, on the premise that the fiber morphology was good. The experimental data is shown in Table 2. The histogram of the spinning efficiency is shown in Fig. 3. For 18 wt% PCL solution, the spinning efficiency of solution blow spinning is about 6 times that of electrospinning. For 10 wt% PVB solution and 22 wt% PMMA solution, the spinning efficiency of solution blowing spinning is about 5 times that of electrospinning. For 12 wt% PVP solution, the spinning efficiency of the solution blow spinning is 8 times that of the electrospinning efficiency. Although the portable solution blow spinning device has higher spinning efficiency, the average diameter of the spun fibers
Table 2 Spinning efficiency of solution blow spinning (SBS) and electrospinning (ES). Polymer solution
PCL (18 wt%) PVB (10 wt%) PMMA (22 wt%) PVP (12 wt%)
Solution weight consumed in one minute (g min−1) Electrospinning (ES)
Solution blow spinning (SBS)
0.0501 0.0771 0.0618 0.0242
0.2994 0.4058 0.3100 0.1970
Fig. 3. Histogram of spinning efficiency of solution blow spinning and electrospinning.
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Fig. 5. SEM images and diameter distribution of PVB fibers. The spinning distance is (a) 20 cm, (b) 30 cm, (c) 40 cm. (d) The relationship between the average diameter of the fibers and the spinning distance (error bars represent the standard deviation of the fibers diameter).
Fig. 4. SEM images and diameter distribution of the PVB fibers. The solution concentration of PVB is (a) 7 wt%, (b) 10 wt%, (c) 13 wt%. (d) The relationship between the average diameter of the fiber and the solution concentration (error bars represent the standard deviation of the fibers diameter).
solvent. Therefore, the spinning distance is one of the important factors affecting the morphology and diameter of the fibers. In this experiment, PVB fibers were prepared at a receiving distance of 20 cm, 30 cm, and 40 cm using the device we designed, and the concentration of the PVB solution was 10 wt%. The SEM images of the fibers is shown in Fig. 5ac. As shown in Fig. 5d, as the spinning distance increases, the average diameter of the fibers decreases from 2.43 μm to 1.95 μm. This is because the shorter the spinning distance, the shorter the solvent volatilization time and the insufficient refinement of the solution jet, so the diameter of the fibers increases. Fig. 6 is FTIR spectra of polymer fibers. From Fig. 6a, we can get the chemical structure of PVP. OeH stretching vibration peak at 3442 cm−1, CeH stretching vibration peak at 2954 cm−1, C]O stretching vibration absorption peak at 1650 cm−1, CeH bending vibration absorption peak and C-N stretching vibration absorption peak at 1426 cm−1 and 1287 cm−1, respectively [29–31]. The FTIR spectra of PCL fibers is shown in Fig. 6b. The peak at 1288 cm−1 is CeO and CeC stretching, the peak at 1238 cm−1 corresponding to asymmetric COC stretching, and the characteristic peak at 2953 cm−1, 2865 cm−1, 1727 cm−1 corresponding to the asymmetric CH2 stretching, the symmetric CH2 stretching and the carbonyl stretching [32–34]. Therefore, the chemical properties of PVP and PCL before and after spinning did not change, thus demonstrating that the designed device does not change the chemical properties of the polymer.
by the portable device is thicker than those prepared by electrospinning. Particularly, electrospinning can produce ultrafine fibers with diameter below 100 nm [25–27], which is a challenge for the solution blow spinning. 3.2. Influence of polymer solution concentration It is well known that the properties of the spinning solution are important for solution blow spinning, and the concentration of the spinning solution is an important factor affecting the properties of the spinning solution [22,28]. We prepared PVB solution with concentration of 7 wt%, 10 wt% and 13 wt%, respectively. Then used the device designed by us for spinning. The spinning distance was 30 cm. The SEM images of the fibers and the relationship between the diameter of the fibers and the concentration of the solution are shown in Fig. 4. The average diameter of the fibers was 0.69 μm (7 wt%), 2.17 μm (10 wt%), and 2.37 μm (13 wt%), respectively. Therefore, as the concentration of the solution increases, the fiber diameter also gradually increases. In addition, from Fig. 4a, we can see that the fibers obtained from the PVB solution with concentration of 7 wt% contain some beads and some fibers are adhering together. As the solution concentration increases from 7 wt% to 10 wt%, the bead structure gradually disappears, and the morphology of the fiber also becomes better. These changes of fibers can be attributed to the concentration of solution lower concentration of solution leads to incomplete volatilization of solvents, and thus the appearance of bead structure. However, the lower the concentration of the solution, the lower the viscosity of the solution, and the solution jet will be more refined by the high pressure airflow, thus reducing the diameter of the fibers.
3.4. Application of portable solution blow spinning device As shown in Fig. 7, the PCL fibers can be rapidly spun onto a human hand (in 25 s) (the related video can be found in Video S3) or wound surface of a pig liver (in 90 s) using our designed portable device. As shown in Fig. 7c, the PCL fibrous membrane has good flexibility. In addition, it was found that the deposited fibrous membrane had good adhesion on the liver surface. As shown in Fig. S1, the surface of the liver was covered by a piece of surgical gauge (3 cm × 3 cm), and then a layer of PCL fibrous membrane was deposited on the surface with the portable device. Finally, the pig liver (~400 g) could be hung by hooking the surgical gauze with a tweezer. The adhesion between
3.3. Influence of spinning distance In the solution blow spinning process, the spinning distance is the distance from the pointer to the receiving plate, which determines the moving distance of the solution jet and the volatilization time of the 4
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Fig. 6. FTIR spectra of the polymer fibers. (a) FTIR spectra of PVP fibers. (b) FTIR spectra of PCL fibers.
Fig. 8. (a) Scene photo of laparoscopic surgery. (b) Schematic diagram of laparoscopic surgery. (c) Schematic diagram of a coaxial long needle portable solution blow spinning device. The illustration is an SEM image of the fibers of the medical glue. (d) Pig liver wound before spinning. (e) Spinning medical glue fibers onto the surface of pig liver wound. HE staining, normal pig liver (f, g), solution blow spinning (f', g'). (f and f' original magnification ×10; g and g' original magnification ×40).
Fig. 7. (a) The hand before spinning fibers. (b) The hand after spinning PCL fibers for 25 s. (c) The PCL fibrous membrane could be removed from the hand. (d) Pig liver before spinning fibers. (e) The PCL fibrous membrane was spun onto the wound surface of the pig liver in 90 s.
fibrous membrane and organs is sufficient, and it can meet normal needs. Because the spinning efficiency of the portable SBS device is much faster than that of previously reported portable electrospinning devices [18,19,34–39], and the device can spin fibers onto the surface of human skin and animal liver, the device can be applied to in situ rapid wound dressing. The hemostatic material used in laparoscopic liver hemostasis surgery and spinal surgery is the rapid medical glue α-cyanoacrylate, this material degrades into water-soluble cyanoacrylic acid and formic acid, which is then excreted in the urine for about one month. The schematic diagram of the portable solution blow spinning device with coaxial long needle is shown in Fig. 8c. The inner needle of the coaxial long needle has an inner diameter of 0.6 mm and a length of 35.15 cm. The outer needle has an inner diameter of 2.5 mm and a length of 35 cm. For laparoscopic liver hemostasis experiments, in order to prevent the abdominal cavity expansion of the pig, we use the method of intermittently pressing the dust removing tank switch. Fig. 8e shows the pig liver wound after spinning (the related video can be found in Video S4). Compared with Fig. 8d, we can see that the hemostasis effect is very good. Seven days after surgery, the pig’s liver was excised and fixed in 4% neutral formalin solution. The desired regions were excised, embedded in paraffin, and stained with hematoxylin and eosin. Fig. 8f-g' is HE staining of pig liver after seven days, and it can be seen from Fig. 8f' that the hepatic lobules are in good shape, and Fig. 8g' shows that the hepatocytes are arranged in an orderly manner and only a small part of the inflammation exists. Such good experimental results prove that the device can be applied to laparoscopic hemostasis surgery. For spinal surgery in pig, we first suture the wound and then stop bleeding after
suturing. The experimental images are shown in Fig. 9a-d (the related video can be found in Video S5). Comparing Fig. 9c with Fig. 9d, it can be seen that the hemostatic effect is very significant.
4. Conclusions In summary, we have designed a portable solution blow spinning device with a dust removing tank as a high-pressure air source. The device is electricity free, simple and portable, and the spinning efficiency is high. The portable device has been experimentally proven to have a higher spinning efficiency than that of the conventional singleneedle electrospinning device. In addition, a variety of polymers have been successfully spun into ultrafine fibers using the new apparatus, and the effects of solution concentration and spinning distance on fibers morphology have also been studied. After that, in order to solve the problem that electrospinning requires high-voltage electricity and easy to damage the medical instruments, a portable solution blow spinning device with coaxial long needle was proposed. And we performed laparoscopic liver hemostasis surgery and spinal surgery to prove the feasibility of the device. The experimental results show that the device has good stability and feasibility, and has potential applications in rapid wound dressing and hemostasis, especially combined with laparoscopy for liver hemostasis.
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Fig. 9. (a) Pig spinal cord. (b) Sutured pig spine wound. (c) Wound before spinning. (d) Wound after spinning.
Declaration of Competing Interest
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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgement This work was supported by the National Natural Science Foundation of China (51973100, 51703102 and 81802190), and the Postdoctoral Science Foundation of China (2019M652329). Animal Rights Animal experiments we conducted complied with the ARRIVE guidelines, and in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/ 63/EU for animal experiments. And we complied with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978). Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.cej.2020.124052. References [1] J. Jiang, S. Chen, H. Wang, M.A. Carlson, A.F. Gombart, J. Xie, CO2-expanded nanofiber scaffolds maintain activity of encapsulated bioactive materials and promote cellular infiltration and positive host response, Acta Biomaterialia 68 (2018) 237–248. [2] A. Nasajpour, S. Ansari, C. Rinoldi, A.S. Rad, T. Aghaloo, S.R. Shin, Y.K. Mishra, R. Adelung, W. Swieszkowski, N. Annabi, A multifunctional polymeric periodontal membrane with osteogenic and antibacterial characteristics, Adv. Funct. Mater. 28 (2018) 1703437. [3] L. Wang, J. Yang, B. Ran, X. Yang, W. Zheng, Y. Long, X. Jiang, Small molecular TGF-β1-inhibitor-loaded electrospun fibrous scaffolds for preventing hypertrophic scars, ACS Appl. Mater. Interfaces 9 (2017) 32545–32553. [4] J.E. Efome, D. Rana, T. Matsuura, C.Q. Lan, Insight studies on metal-organic framework nanofibrous membrane adsorption and activation for heavy metal ions removal from aqueous solution, ACS Appl. Mater. Interfaces 10 (2018) 18619–18629. [5] X. Li, X.-X. Wang, T.-T. Yue, Y. Xu, M.-L. Zhao, M. Yu, S. Ramakrishna, Y.-Z. Long, Waterproof-breathable PTFE nano- and microfiber membrane as high efficiency PM2. 5 filter, Polymers 11 (2019) 590. [6] Q. Wang, J. Ju, Y. Tan, L. Hao, Y. Ma, Y. Wu, H. Zhang, Y. Xia, K. Sui, Controlled synthesis of sodium alginate electrospun nanofiber membranes for multi-occasion adsorption and separation of methylene blue, Carbohydr. Polym. 205 (2019) 125–134. [7] Z.-G. Zhang, H. Liu, X.-X. Wang, J. Zhang, M. Yu, S. Ramakrishna, Y.-Z. Long, Onestep low temperature hydrothermal synthesis of flexible TiO2/PVDF@MoS2 coreshell heterostructured fibers for visible-light-driven photocatalysis and selfcleaning, Nanomaterials 9 (2019) 431. [8] Y. Zhao, J. Liang, C. Wang, J. Ma, G.G. Wallace, Tunable and efficient tin modified nitrogen-doped carbon nanofibers for electrochemical reduction of aqueous carbon dioxide, Adv. Energy Mater. 8 (2018) 1702524. [9] Y. Fu, H.Y. Yu, C. Jiang, T.H. Zhang, R. Zhan, X. Li, J.F. Li, J.H. Tian, R. Yang, NiCo alloy nanoparticles decorated on N-doped carbon nanofibers as highly active and durable oxygen electrocatalyst, Adv. Funct. Mater. 28 (2018) 1705094. [10] M.-F. Lin, J. Xiong, J. Wang, K. Parida, P.S. Lee, Core-shell nanofiber mats for tactile pressure sensor and nanogenerator applications, Nano Energy 44 (2018) 248–255.
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[37] W.-P. Han, Y.-Y. Huang, M. Yu, J.-C. Zhang, X. Yan, G.-F. Yu, H.-D. Zhang, S.Y. Yan, Y.-Z. Long, Self-powered electrospinning apparatus based on a hand-operated Wimshurst generator, Nanoscale 7 (2015) 5603–5606. [38] X.X. Wang, W.-Z. Song, M.-H. You, J. Zhang, M. Yu, Z. Fan, S. Ramakrishna, Y.Z. Long, Bionic single-electrode electronic skin unit based on piezoelectric nanogenerator, ACS Nano 12 (2018) 8588–8596. [39] B. Zhang, X. Yan, H.-W. He, M. Yu, X. Ning, Y.-Z. Long, Solvent-free electrospinning: opportunities and challenges, Polymer Chem. 8 (2017) 333–352.
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A portable solution blow spinning device for minimally invasive surgery hemostasis
T
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Yuan Gaoa,1, Hong-Fei Xianga,b,1, Xiao-Xiong Wanga, , Kang Yana, Qi Liua, Xin Lia, ⁎ Rui-Qiang Liua, Miao Yua,c, Yun-Ze Longa, a
Collaborative Innovation Center for Nanomaterials & Devices, College of Physics, Qingdao University, Qingdao 266071, China Department of Spine Surgery, Affiliated Hospital of Qingdao University, Qingdao 266071, China c Department of Mechanical Engineering, Columbia University, New York, NY 10027, United States b
H I GH L IG H T S
solved the problems of electrospinning technology in minimally invasive surgery. • Successfully solution blow spinning device was proposed for the first time. • ATwoportable • applications have been proposed, namely in situ rapid wound dressing and minimally invasive surgical visceral hemostasis.
A R T I C LE I N FO
A B S T R A C T
Keywords: Solution blow spinning Minimally invasive surgery Portable device Hemostasis Laparoscopic
In situ fiber deposition technology has shown great excellence in visceral hemostasis. In recent years, minimally invasive surgery has been widely welcomed by patients because of its small trauma, light pain and rapid recovery. In the treatment of minimally invasive surgical wounds, fiber deposition has the advantages of fast, convenient, disassemble free and low toxicity. However, due to the conductive nature of the human body and narrow space in thoracic and abdominal cavity, the use of electrospinning technology to deposit fibers have high risk of short circuit and creepage. Such adverse effects, on the one hand, bring dangers to patients, and on the other hand, they will destroy equipment such as endoscopes. In this work, we used gas-blowing spinning instead of high-voltage electricity to guide fiber deposition, and completed liver hemostasis in a minimally invasive surgical environment. Pathological section analysis revealed that the surgery did not trigger an additional inflammatory response. It is worth mentioning that the gas blowing system used in this work can be a portable one. The high pressure gas source is changed from a conventional air pump to a commercially available compressed gas bottle (weight ~284 g, air pressure ~0.6 MPa). The gas source is greatly optimized and the volume is smaller. It is more convenient to carry, which makes the combination of hemostasis and other surgical items more convenient. This method is similar to the hemostatic membrane prepared by electrospinning technology, which can avoid the use of drainage tube, thus providing a cutting-edge form for minimally invasive surgery.
1. Introduction Nanofibers have been widely used in biomedical engineering [1–3], filtration [4–6], catalysis [7,8], energy [9–11], food engineering [12] and other fields due to their excellent properties. In situ nanofiber deposition technology can deposit nanofibers on the wound surface [13]. By forming a fiber membrane that is light, thin and adhering well to the wound, rapid and large-area hemostasis can be achieved, especially for soft tissue hemostasis such as viscera [14]. Compared with traditional
hemostasis methods such as electrocoagulation, fusion, etc., hemostatic surface obtained by nanofiber deposition is more reliable, having lower risk of secondary bleeding. It does not cause new damage to the tissue, and the toxicity is very low [15]. To give an example, electrospinning (ES) technology is a well-known method which can directly and continuously prepare nanofibers. Its principle is to stretch and refine polymer solution or melt by electric field force, and then obtain nanofibers [16,17]. By using portable or handheld electrospinning apparatus [18], the in situ electrospinning technique can deposit nanofibers
⁎
Corresponding authors. E-mail addresses: [email protected] (X.-X. Wang), [email protected] (Y.-Z. Long). 1 These two authors contributed to this work equally. https://doi.org/10.1016/j.cej.2020.124052 Received 1 November 2019; Received in revised form 31 December 2019; Accepted 4 January 2020 Available online 09 January 2020 1385-8947/ © 2020 Elsevier B.V. All rights reserved.
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onto the wound surface using an electric field. Nanoscale fibers can greatly enhance the van der Waals interaction between the surface of the tissue and the fibers, thus producing good adhesion [19]. Due to the small pore size of these hydrophobic fibers, the surface tension is sufficient to prevent blood outflow. In addition, blood cells are difficult to pass through these fibers, and fibrin can be attached to the porous structure, so a thin layer of fiber can be used to complete the hemostasis [20]. The fibers itself is degradable, and because of the low deposition amount, the toxicity of the tissue is extremely light, so the hemostatic method has an absolute advantage over other method such as the smear method [21]. This technology provides a modern and efficient technique for visceral hemostasis, and even avoids the use of drainage tubes, thus greatly reducing the secondary damage to patients and leading to less pain. As a typical means of low pain surgery, minimally invasive surgery has been widely welcomed by patients because of its small trauma, light pain, and rapid recovery. However, unlike traditional open surgery, the manipulating space during minimally invasive surgery is narrow. Considering that the human body is electrically conductive, electric field deposition of nanofibers can easily lead to short circuit and discharge with human tissues. And because of the integration of a variety of surgical instruments and electronic devices around the endoscope portion of during minimally invasive surgery, high-voltage electrodes of several thousand volts can easily burn the equipment. Therefore, minimally invasive surgery requires an in-situ nanofiber deposition technology that does not use high-voltage electricity. As another typical nanofiber deposition technology, gas-blowing spinning can also assist in the deposition of nanofibers. The high-speed gas stream is used instead of the high-voltage electricity to blow out the polymer precursor, and the fiber is stretched to a very fine shape under the repeated stretching of the turbulent gas stream. When using a solution, this technique is called solution blow spinning (SBS) [22]. It is conceivable that this technology can replace the high-voltage electricity to complete the minimally invasive surgery and avoid the damage of the high-voltage electricity to the human body and equipment. In addition, the high-speed airflow can blow out the precursor faster, so that more fibers can be deposited in a shorter time than electrospinning [23], thereby completing the hemostasis faster. In this work, we use a small dust removing tank instead of a huge air compressor or cylinder, and use a special gas conduit to complete the solution blow spinning process, so the volume of SBS is greatly reduced, which is more conducive to the integration of the equipment onto a tiny cavity lens. Animal experiments were performed using a pig to simulate hemostasis after liver tumor removal under minimally invasive surgery. The results showed that this method has a good hemostasis effect and does not induce tissue inflammation. The high velocity airflow is concentrated at the nozzle and is quickly attenuated without damaging the tissue.
materials and corresponding solvents were weighed by an electronic balance, and then they were mixed and stirred on a magnetic stirrer. After the polymer material was completely dissolved, we used the obtained polymer solution to spin at room temperature. In addition, we used the rapid medical glue α-cyanoacrylate (made by Guangzhou Baiyun Medical Glue Co., Ltd.) for the hemostatic material. This material is composed of N-octyl-2-cyanoacrylate and medical grade polymethyl methacrylate (PMMA, an additive to increase viscosity). 2.2. Solution blow spinning device Fig. 1 is the schematic diagram of the solution blow spinning device which was designed by the authors. The device consists of four parts: a dust removing tank (made by Shanghai Zhantu Chemical Co., Ltd.), a plastic thin tube with inner diameter of 2.8 mm, a syringe and a special curved needle. The plastic thin tube was connected to the outlet of the dust removing tank, and the needle of the syringe and the plastic thin tube were designed to be coaxial. When the apparatus was used, the syringe was pushed to cause the polymer solution to flow out while the trigger of the dust removing tank was pulled, thereby causing the polymer solution to form fibers under the action of a high pressure gas stream. In order to obtain a good spinning effect, the distance between the needle and the collecting plate was controlled between 20 cm and 40 cm. 2.3. Characterization The fiber morphology of the polymer fibers obtained by the designed apparatus can be examined by scanning electron microscopy (SEM, TM-1000, Hitachi). PVP and PCL fibers was also examined by Fourier transform infrared spectroscopy (FTIR, Thermo Scientific Nicolet iN10). The solution jet were recorded by a high-speed digital video camera (FASTCAM Mini UX100, Photron). The average diameter and diameter distribution of the fibers were measured by the software Nano measure 1.2 (the number of fibers measured was 30). The experimental data were processed by the software Origin2018 to obtain histogram of spinning efficiency, histogram of fiber changes with solution concentration and distance. 3. Results and discussion 3.1. Performance of the portable SBS device Similar to electrospinning, solution blow spinning also have solution jet. For the motion of solution jet, Eroglu et al. [24] have done a series of studies and proposed a formula:
L/ d = 0.5We−0.4R e 0.6
(1)
We and R e are Weber number and Reynolds number, respectively. Their definitions are as follows: 2. Experimental 2.1. Materials
We = dρa ur 2/2σ
(2)
R e = dρl ul / μl
(3)
where L is the intact length; d is needle inner diameter; ρa is the gas density; ur is the relative velocity between the solution jet and gas; σ is the surface tension of solution; ρl , ul and μl are the density of the
Table 1 shows the materials used in our experiments to prepare polymer solutions (all chemicals and solvents were of analytical grade and used without further purification). A certain proportion of polymer Table 1 Polymer solution used in the experiment. Polymer
Details
Polyvinyl pyrrolidone, PVP Polycaprolactone, PCL Polymethyl methacrylate, PMMA Polyvinyl butyral, PVB
MW MW MW MW
= = = =
1 300 000 g mol−1, ACROS 100 000 g mol−1, ACROS 210 000 g mol−1, ACROS 90000–120000 g mol−1, ACROS
2
Solvent
Concentration
Anhydrous ethanol Acetone Dimethylformamide (DMF) Anhydrous ethanol
13 wt% 18 wt% 22 wt% 7, 10, 13 wt%
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Fig. 1. Schematic diagram of the portable solution blow spinning device. Fig. 2. (a) Solution jet image taken with a high-speed digital video camera at a parameter of 8000 frames per second. (b) Solution jet image taken with a highspeed digital video camera at a parameter of 20,000 frames per second. SEM images of polymer fibers: (c) PCL, (d) PMMA, (e) PVP, (f) PVB, which were produced by the designed portable solution blow spinning device.
solution, the velocity of the jet and the viscosity of the solution, respectively. Eroglu et al. [24] found that the intact length (L ) of the solution jet became shorter as We increased and became longer as R e increased. Therefore, the high pressure airflow can cause the solution jet to undergo unstable bending and swing. The solution jet produced by the designed device is shown in Fig. 2. It can be seen that the motion of solution jet is an unstable swing (the vivid details can be found in Videos S1 and S2). Therefore, the motion of solution jet conforms to the above theory. In order to verify the practicability of the device we designed, we used the device to spin PCL (18 wt%), PMMA (22 wt%), PVP (13 wt%), and PVB (10 wt%) into fibers. The distance between the spinning needle and collector was 30 cm. The SEM images of the fibers is shown in Fig. 2c-f. The average diameter of the fibers were 1.27 μm (PCL), 1.11 μm (PMMA), 2.21 μm (PVP) and 1.80 μm (PVB), and the fiber diameter distribution is relatively concentrated, indicating that the fiber thickness is uniform. Therefore, the device we designed was proven to be feasible. High spinning efficiency is one of the advantages of solution blow spinning. Therefore, the spinning efficiency of the portable SBS device and the conventional electrospinning device were compared. We recorded the maximum weight of the polymer solution consumed by the two devices in one minute, on the premise that the fiber morphology was good. The experimental data is shown in Table 2. The histogram of the spinning efficiency is shown in Fig. 3. For 18 wt% PCL solution, the spinning efficiency of solution blow spinning is about 6 times that of electrospinning. For 10 wt% PVB solution and 22 wt% PMMA solution, the spinning efficiency of solution blowing spinning is about 5 times that of electrospinning. For 12 wt% PVP solution, the spinning efficiency of the solution blow spinning is 8 times that of the electrospinning efficiency. Although the portable solution blow spinning device has higher spinning efficiency, the average diameter of the spun fibers
Table 2 Spinning efficiency of solution blow spinning (SBS) and electrospinning (ES). Polymer solution
PCL (18 wt%) PVB (10 wt%) PMMA (22 wt%) PVP (12 wt%)
Solution weight consumed in one minute (g min−1) Electrospinning (ES)
Solution blow spinning (SBS)
0.0501 0.0771 0.0618 0.0242
0.2994 0.4058 0.3100 0.1970
Fig. 3. Histogram of spinning efficiency of solution blow spinning and electrospinning.
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Fig. 5. SEM images and diameter distribution of PVB fibers. The spinning distance is (a) 20 cm, (b) 30 cm, (c) 40 cm. (d) The relationship between the average diameter of the fibers and the spinning distance (error bars represent the standard deviation of the fibers diameter).
Fig. 4. SEM images and diameter distribution of the PVB fibers. The solution concentration of PVB is (a) 7 wt%, (b) 10 wt%, (c) 13 wt%. (d) The relationship between the average diameter of the fiber and the solution concentration (error bars represent the standard deviation of the fibers diameter).
solvent. Therefore, the spinning distance is one of the important factors affecting the morphology and diameter of the fibers. In this experiment, PVB fibers were prepared at a receiving distance of 20 cm, 30 cm, and 40 cm using the device we designed, and the concentration of the PVB solution was 10 wt%. The SEM images of the fibers is shown in Fig. 5ac. As shown in Fig. 5d, as the spinning distance increases, the average diameter of the fibers decreases from 2.43 μm to 1.95 μm. This is because the shorter the spinning distance, the shorter the solvent volatilization time and the insufficient refinement of the solution jet, so the diameter of the fibers increases. Fig. 6 is FTIR spectra of polymer fibers. From Fig. 6a, we can get the chemical structure of PVP. OeH stretching vibration peak at 3442 cm−1, CeH stretching vibration peak at 2954 cm−1, C]O stretching vibration absorption peak at 1650 cm−1, CeH bending vibration absorption peak and C-N stretching vibration absorption peak at 1426 cm−1 and 1287 cm−1, respectively [29–31]. The FTIR spectra of PCL fibers is shown in Fig. 6b. The peak at 1288 cm−1 is CeO and CeC stretching, the peak at 1238 cm−1 corresponding to asymmetric COC stretching, and the characteristic peak at 2953 cm−1, 2865 cm−1, 1727 cm−1 corresponding to the asymmetric CH2 stretching, the symmetric CH2 stretching and the carbonyl stretching [32–34]. Therefore, the chemical properties of PVP and PCL before and after spinning did not change, thus demonstrating that the designed device does not change the chemical properties of the polymer.
by the portable device is thicker than those prepared by electrospinning. Particularly, electrospinning can produce ultrafine fibers with diameter below 100 nm [25–27], which is a challenge for the solution blow spinning. 3.2. Influence of polymer solution concentration It is well known that the properties of the spinning solution are important for solution blow spinning, and the concentration of the spinning solution is an important factor affecting the properties of the spinning solution [22,28]. We prepared PVB solution with concentration of 7 wt%, 10 wt% and 13 wt%, respectively. Then used the device designed by us for spinning. The spinning distance was 30 cm. The SEM images of the fibers and the relationship between the diameter of the fibers and the concentration of the solution are shown in Fig. 4. The average diameter of the fibers was 0.69 μm (7 wt%), 2.17 μm (10 wt%), and 2.37 μm (13 wt%), respectively. Therefore, as the concentration of the solution increases, the fiber diameter also gradually increases. In addition, from Fig. 4a, we can see that the fibers obtained from the PVB solution with concentration of 7 wt% contain some beads and some fibers are adhering together. As the solution concentration increases from 7 wt% to 10 wt%, the bead structure gradually disappears, and the morphology of the fiber also becomes better. These changes of fibers can be attributed to the concentration of solution lower concentration of solution leads to incomplete volatilization of solvents, and thus the appearance of bead structure. However, the lower the concentration of the solution, the lower the viscosity of the solution, and the solution jet will be more refined by the high pressure airflow, thus reducing the diameter of the fibers.
3.4. Application of portable solution blow spinning device As shown in Fig. 7, the PCL fibers can be rapidly spun onto a human hand (in 25 s) (the related video can be found in Video S3) or wound surface of a pig liver (in 90 s) using our designed portable device. As shown in Fig. 7c, the PCL fibrous membrane has good flexibility. In addition, it was found that the deposited fibrous membrane had good adhesion on the liver surface. As shown in Fig. S1, the surface of the liver was covered by a piece of surgical gauge (3 cm × 3 cm), and then a layer of PCL fibrous membrane was deposited on the surface with the portable device. Finally, the pig liver (~400 g) could be hung by hooking the surgical gauze with a tweezer. The adhesion between
3.3. Influence of spinning distance In the solution blow spinning process, the spinning distance is the distance from the pointer to the receiving plate, which determines the moving distance of the solution jet and the volatilization time of the 4
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Fig. 6. FTIR spectra of the polymer fibers. (a) FTIR spectra of PVP fibers. (b) FTIR spectra of PCL fibers.
Fig. 8. (a) Scene photo of laparoscopic surgery. (b) Schematic diagram of laparoscopic surgery. (c) Schematic diagram of a coaxial long needle portable solution blow spinning device. The illustration is an SEM image of the fibers of the medical glue. (d) Pig liver wound before spinning. (e) Spinning medical glue fibers onto the surface of pig liver wound. HE staining, normal pig liver (f, g), solution blow spinning (f', g'). (f and f' original magnification ×10; g and g' original magnification ×40).
Fig. 7. (a) The hand before spinning fibers. (b) The hand after spinning PCL fibers for 25 s. (c) The PCL fibrous membrane could be removed from the hand. (d) Pig liver before spinning fibers. (e) The PCL fibrous membrane was spun onto the wound surface of the pig liver in 90 s.
fibrous membrane and organs is sufficient, and it can meet normal needs. Because the spinning efficiency of the portable SBS device is much faster than that of previously reported portable electrospinning devices [18,19,34–39], and the device can spin fibers onto the surface of human skin and animal liver, the device can be applied to in situ rapid wound dressing. The hemostatic material used in laparoscopic liver hemostasis surgery and spinal surgery is the rapid medical glue α-cyanoacrylate, this material degrades into water-soluble cyanoacrylic acid and formic acid, which is then excreted in the urine for about one month. The schematic diagram of the portable solution blow spinning device with coaxial long needle is shown in Fig. 8c. The inner needle of the coaxial long needle has an inner diameter of 0.6 mm and a length of 35.15 cm. The outer needle has an inner diameter of 2.5 mm and a length of 35 cm. For laparoscopic liver hemostasis experiments, in order to prevent the abdominal cavity expansion of the pig, we use the method of intermittently pressing the dust removing tank switch. Fig. 8e shows the pig liver wound after spinning (the related video can be found in Video S4). Compared with Fig. 8d, we can see that the hemostasis effect is very good. Seven days after surgery, the pig’s liver was excised and fixed in 4% neutral formalin solution. The desired regions were excised, embedded in paraffin, and stained with hematoxylin and eosin. Fig. 8f-g' is HE staining of pig liver after seven days, and it can be seen from Fig. 8f' that the hepatic lobules are in good shape, and Fig. 8g' shows that the hepatocytes are arranged in an orderly manner and only a small part of the inflammation exists. Such good experimental results prove that the device can be applied to laparoscopic hemostasis surgery. For spinal surgery in pig, we first suture the wound and then stop bleeding after
suturing. The experimental images are shown in Fig. 9a-d (the related video can be found in Video S5). Comparing Fig. 9c with Fig. 9d, it can be seen that the hemostatic effect is very significant.
4. Conclusions In summary, we have designed a portable solution blow spinning device with a dust removing tank as a high-pressure air source. The device is electricity free, simple and portable, and the spinning efficiency is high. The portable device has been experimentally proven to have a higher spinning efficiency than that of the conventional singleneedle electrospinning device. In addition, a variety of polymers have been successfully spun into ultrafine fibers using the new apparatus, and the effects of solution concentration and spinning distance on fibers morphology have also been studied. After that, in order to solve the problem that electrospinning requires high-voltage electricity and easy to damage the medical instruments, a portable solution blow spinning device with coaxial long needle was proposed. And we performed laparoscopic liver hemostasis surgery and spinal surgery to prove the feasibility of the device. The experimental results show that the device has good stability and feasibility, and has potential applications in rapid wound dressing and hemostasis, especially combined with laparoscopy for liver hemostasis.
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Fig. 9. (a) Pig spinal cord. (b) Sutured pig spine wound. (c) Wound before spinning. (d) Wound after spinning.
Declaration of Competing Interest
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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgement This work was supported by the National Natural Science Foundation of China (51973100, 51703102 and 81802190), and the Postdoctoral Science Foundation of China (2019M652329). Animal Rights Animal experiments we conducted complied with the ARRIVE guidelines, and in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/ 63/EU for animal experiments. And we complied with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978). Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.cej.2020.124052. References [1] J. Jiang, S. Chen, H. Wang, M.A. Carlson, A.F. Gombart, J. Xie, CO2-expanded nanofiber scaffolds maintain activity of encapsulated bioactive materials and promote cellular infiltration and positive host response, Acta Biomaterialia 68 (2018) 237–248. [2] A. Nasajpour, S. Ansari, C. Rinoldi, A.S. Rad, T. Aghaloo, S.R. Shin, Y.K. Mishra, R. Adelung, W. Swieszkowski, N. Annabi, A multifunctional polymeric periodontal membrane with osteogenic and antibacterial characteristics, Adv. Funct. Mater. 28 (2018) 1703437. [3] L. Wang, J. Yang, B. Ran, X. Yang, W. Zheng, Y. Long, X. Jiang, Small molecular TGF-β1-inhibitor-loaded electrospun fibrous scaffolds for preventing hypertrophic scars, ACS Appl. Mater. Interfaces 9 (2017) 32545–32553. [4] J.E. Efome, D. Rana, T. Matsuura, C.Q. Lan, Insight studies on metal-organic framework nanofibrous membrane adsorption and activation for heavy metal ions removal from aqueous solution, ACS Appl. Mater. Interfaces 10 (2018) 18619–18629. [5] X. Li, X.-X. Wang, T.-T. Yue, Y. Xu, M.-L. Zhao, M. Yu, S. Ramakrishna, Y.-Z. Long, Waterproof-breathable PTFE nano- and microfiber membrane as high efficiency PM2. 5 filter, Polymers 11 (2019) 590. [6] Q. Wang, J. Ju, Y. Tan, L. Hao, Y. Ma, Y. Wu, H. Zhang, Y. Xia, K. Sui, Controlled synthesis of sodium alginate electrospun nanofiber membranes for multi-occasion adsorption and separation of methylene blue, Carbohydr. Polym. 205 (2019) 125–134. [7] Z.-G. Zhang, H. Liu, X.-X. Wang, J. Zhang, M. Yu, S. Ramakrishna, Y.-Z. Long, Onestep low temperature hydrothermal synthesis of flexible TiO2/PVDF@MoS2 coreshell heterostructured fibers for visible-light-driven photocatalysis and selfcleaning, Nanomaterials 9 (2019) 431. [8] Y. Zhao, J. Liang, C. Wang, J. Ma, G.G. Wallace, Tunable and efficient tin modified nitrogen-doped carbon nanofibers for electrochemical reduction of aqueous carbon dioxide, Adv. Energy Mater. 8 (2018) 1702524. [9] Y. Fu, H.Y. Yu, C. Jiang, T.H. Zhang, R. Zhan, X. Li, J.F. Li, J.H. Tian, R. Yang, NiCo alloy nanoparticles decorated on N-doped carbon nanofibers as highly active and durable oxygen electrocatalyst, Adv. Funct. Mater. 28 (2018) 1705094. [10] M.-F. Lin, J. Xiong, J. Wang, K. Parida, P.S. Lee, Core-shell nanofiber mats for tactile pressure sensor and nanogenerator applications, Nano Energy 44 (2018) 248–255.
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