Robot-aided electrospinning toward intelligent biomedical engineering
© The Author(s) 2017
Received: 6 October 2017
Accepted: 1 November 2017
Published: 10 November 2017
The rapid development of robotics offers new opportunities for the traditional biofabrication in higher accuracy and controllability, which provides great potentials for the intelligent biomedical engineering. This paper reviews the state of the art of robotics in a widely used biomaterial fabrication process, i.e., electrospinning, including its working principle, main applications, challenges, and prospects. First, the principle and technique of electrospinning are introduced by categorizing it to melt electrospinning, solution electrospinning, and near-field electrospinning. Then, the applications of electrospinning in biomedical engineering are introduced briefly from the aspects of drug delivery, tissue engineering, and wound dressing. After that, we conclude the existing problems in traditional electrospinning such as low production, rough nanofibers, and uncontrolled morphology, and then discuss how those problems are addressed by robotics via four case studies. Lastly, the challenges and outlooks of robotics in electrospinning are discussed and prospected.
The basic idea of electrospinning originated in the period from 1934 to 1944, when researchers describes the use of electrostatic force to produce polymer filament device. The main principle is using high-voltage electrostatic field to stimulate the polymer charged jet and then to obtain the polymer nanofibers by charged jet curing. From the middle of the twentieth century to present, electrospinning technology ended up more than 60 years of silence, and finally in the last decade of twentieth century ushered in its glorious era. In 1994, “electrospinning” became a professional term, instead of “electrostatic spinning,” officially declared electrospinning as an independent academic field, began its research and development in the field of nanotechnology and related bioengineering. At present, electrospinning is rapidly emerging as a unique and versatile technique for the preparation of smooth nanofibers with controllable morphology from various polymers [1, 2]. The nanofibers produced by electrospinning have high surface area and highly porous structure, and furthermore, design flexibility is an important advantage of electrospun nanofibers .
Electrospinning has widely been used in biomedical engineering, including wound dressings, filtration, and drug delivery systems, as well as tissue engineering scaffolds . Electrospinning process depends on several parameters, including  the properties of solution (viscosity, elasticity, electrical conductivity, and surface tension), applied voltage, nozzle–collector distance, ejection speed, surrounding temperature, humidity, air flow rate, etc. Therefore, the precise control of each parameter directly affects the morphology of the nanofibers . In vivo, tissue engineering scaffolds must be not only a three-dimensional structure which is required to mimic extracellular matrix but also a high porosity, large surface area, suitable pore size, and highly interconnected pore structure . Therefore, it is challenging for the traditional electrospinning method to obtain such biocompatibility, biodegradability, non-toxicity, and structural integrity scaffolds precisely due to the randomly intertwined nanofibers [8, 9]. Hence, the urgent requirement on electrospinning is how to precisely control the morphology and diameter of electrospinning so that it can produce thinner nanofibers with the structure of three-dimensional in biomedical engineering.
As an emerging technology, robotics has involved in and benefits many biofabrication process to ensure and improve the accuracy, flexibility, and controllability, such as 3D printing, 3D plotting, nanoimprinting. Robot-aided electrospinning is integrating robot to general electrospinning process to improve the control of parameters, the diameter of nanofibers, the rate of producing nanofibers, and so on. In this review, we summarize the state of the art of electrospinning in biomedical engineering and discuss how the robotics benefit the electrospinning process, i.e., including its working principle, main applications, challenges, and prospects.
Basic principle and technique of electrospinning
As the one of the most straightforward and cost-effective method, electrospinning technique with unique physiochemical property has gained an extensive application in biomedical field [10–12]. An integrated electrospinning device consists of a DC high-voltage supply, a syringe is filled with polymer solution, a needle, and a collector. To fabricate nanofibers, one electrode of DC high-voltage supply is connected to the needle of the syringe, and the polymer is ejected to the target collector from the top of the needle. During the process, the polymer droplets are held by the surface tension at the needle, which collects the charge on the surface induced by the electric field, while it receives an electric field force which is opposite to the surface tension . The droplets are pulled from spherical to cone-shaped structure named Taylorcone. However, the electric field force will overcome the surface tension of the liquid when it increases to a critical value . The polymer jet occurs under the influence of high electric field, resulting in extremely high-frequency irregular spiral motion . Ultimately, a fiber of nanometer diameter is formed and scattered on the collector in a random manner to form a non-woven fabric .
Melt electrospinning and solution electrospinning
Solution electrospinning is well known for its simplicity of operation and suitability for many polymers. The jet of solution electrospinning has the virtue of low viscosity and is easy to obtain nanofibers with diameter less than 100 nm. Besides, the surface of fiber presents the porous structure due to solvent evaporation . The advantage of melt electrospinning is that there is no need to find the solvent for dissolving polymer, and the end-product is suitable for the application of biomedical engineering such as tissue engineering and drug release. In a sense, it is easy to realize the mass production due to not require the use of volatile solvents [18, 19]. While comparing these two approaches, solution electrospinning is facing the challenges of significant solvent evaporation, difficult direct-writing, and low output. In these and several respects, as a kind of raw materials with wide applicability, favorable direct-writing capability, non-toxic pollution, and high conversion rate of product technology, the melt electrospinning handles better than the solution electrospinning, but it requires severe external conditions like higher spinning temperature, more time to build, and heat-resistant polymers .
Nevertheless, these two techniques are difficult to achieve the requirement of high-precision pattern and structure when the polymer steps into the instability motion and splitting process  since the high voltage (≤ 10 kV) limits softness of nanofibers and choice of polymer materials. Finally, this could lead to create randomly coiled fibers and form uncontrolled construction. The next, the solution of spinning issues caused by the high voltage is presented.
Comparison between SES/MES and NFSE 
Fiber diameter (μm)
Melt electrospinning and solution electrospinning
Various applicable materials
Although near-field electrospinning is termed a best tool to deposit solid nanofibers in using direct-write, it is not capable enough to fabricate mass production with its single nozzle; moreover, it is easy to cause fiber diameters become thicker because of shortening spinneret-to-substrate distance . Facing this a series of questions, researchers are using robot-aided for realizing large-scale production of electrospinning, and thinner nanofibers will be applied in much more fields.
Applications of electrospinning in biomedical engineering
The main function of electrospinning technology is to prepare polymer nanofibers, which can be then designed to biomedical material, nanosensor, and nanofiber templates. As the nanofiber mats prepared by electrospinning has the characteristics of high surface-to-volume ratio, high porosity, and relatively uniform fiber diameter, it has a unique property in its application. Also, the electrospinning mats has a favorable bionic property including high biocompatibility. Then, this thesis illustrates the application in three fields.
Applications for drug delivery
On this aspect of using multilayered drug-loaded biodegradable nanofiber, Tatsuya et al.  developed the use of multilayered drug-loaded biodegradable nanofiber as a drug carrier material, by controlling the diameter of the fiber and the thickness of non-drug layer to achieve the purpose of controlled release. Meanwhile, making use of nanofibers prepared with the corresponding material as a drug carrier material can also achieve this aim.
Although a wide variety of drugs for the treatment of diseases have been successfully encapsulated into these nanofibers, significant progress has been made in the use of electrospun fibers for drug delivery, and many problems remain to be resolved. First, in order to produce uniform nanofibers with favorable morphological, mechanical and chemical properties for realizing its repeated and massive production are the challenge. Second, how to make drug-loading content properly and efficiently and removal of residual organic solvent are particularly important . Third, we need to know that nanofibers may cause an immune response or toxicity when applying these nanofibers in vivo.
Applications for tissue engineering
For these reasons, nanofibrous scaffolds with its unique advantages in suitable porosity, nanoscale topography, and interconnectivity, it attracts more and more researchers constantly. About this study of nanofibrous scaffolds that better recapitulate tissue properties and enhance regeneration , numerous research works have been done and a lot of optimum design methods were presented. A variety of polymeric nanofibers have been considered for use as scaffolds for engineering tissues like skin tissue engineering [45, 46], bones [47, 48], vessels [49, 50], heart [51, 52], etc. In 2011, Szentivanyi et al. developed a cost-efficient and versatile approach to generate three-dimensional scaffolds of different shape and size . Basu et al. succeed in researching and producing PEO and CMC/PEO nanofibrous scaffolds with 3D porous network using electrospinning technique. In addition, it is shown experimentally that nanofibrous scaffolds have thermally stable characters and the appreciable tensile properties for cell adherence and growth. MTT experimental results show that nanofibrous scaffolds possess the property of non-toxicity and cell proliferation .
However, there are several challenges that need to be solved prior to use of electrospun grafts in clinical applications. On the aspects of improving nanofibrous scaffolds, we should consider some important parameters such as fiber formation, morphology, composition, as well as homogenous cell distributions. Accurate bionic scaffold is the goal that researchers have been hoping to achieve.
Besides, the lack of cellular infiltration continues to be the key of research with new techniques developed to solve this challenge including dropping fiber packing density, multilayered electrospinning, dynamic cell culture, and cell electrospraying .
Applications for wound dressing
The electrospun non-woven mat was fabricated by electrospinning which is a unique and versatile technique. It possesses lots of advantages such as high air permeability, high liquid absorption rate, and the flexible fitness to the wound site [55, 56]. In addition, electrospun non-woven was regarded as material to be used in wounding-healing process , because it can keep the wounds dry and prevent them from infection . Melaiye et al.  developed electrospun nanofibers as carrier and loaded-silver imidazole ring composite, and their anti-bacterial action was studied for wound-healing materials. Hong and Kyung Hwa reported a PVA/Ag composite nanofiber mats as wound repair materials, due to the bactericidal effect of Ag nanoparticles, and it is possible to prevent wound infection and promote wound healing . Wei et al. introduced the non-woven wound dressing with core–shell structured fibers, which was prepared by coaxial electrospinning and then taking silver nanoparticles (Ag-NPs) into the shell, whereas the vitamin A palmitate (VA), healing-promoting drug, was encapsulated in the core.
However, the need of this non-woven wound dressing for all trauma is not ideal because the skin wound is heterogeneous between the patient groups, and thus the skin regeneration should turn to personalized treatment . In addition, the possibility of its residual solvent is so high, and it is difficult to produce a uniform nanofiber. But it is easy to overcome by adjusting the parameters .
As mentioned above, traditional electrospinning has its merits as well as its limitations and demerits. Firstly, it is difficult for the traditional electrospinning to accurately control the direction of electrospinning and get the specific three-dimensional structure in experiment. Secondly, it is difficult to apply the nanofiber mats in medical engineering directly due to the roughness of the produced nanofiber surface. Beyond that, it also difficult to achieve high productivity due to the individual nozzle. In order to realize the position-controlled deposition and precise integration of individual or aligned fibers with flexible and functional devices , robotics attracted the interest of researchers and attention of the electrospinning field. Robotics provides better ability to move the needle flexibly on the x–y–z axis because of direct computer system control. Under the control of the processing, the precise three-dimensional structure presented in front of the researchers. In addition, robotics induces the change of each parameter in the spinning process from the computer system and further controls the process of electrospinning for keeping the morphology and diameter of nanofibers.
Robot-aided multi-nozzle electrospinning
To improve the efficiency for mass production, researchers proposed robotics multi-nozzle electrospinning technique, which makes it possible to increase the productivity and covering area . In this process, the accuracy is highly affected by the repulsion from the adjacent jets and the non-uniform electric field on Taylorcone of every needle. Around these problems, a number of robot-aided multi-nozzle NFEC apparatus were presented. Many researchers hope to utilize increase the number of nozzle to achieve the robot-aided control of uniform electric field.
A robot-assisted angled multi-nozzle electrospinning device
A robot electrospinning direct-clothing device
These systems could combine robot technology and multi-needle electrospinning and is suitable for using on solution, melt, near-filed electrospinning, and composite electrospinning. The spinning device can be operated along a predetermined path by means of a electrospinning robot induction, feedback, and control combined with a computer program control, and ensures spinning sprinkler head is vertically downward. The computer control device is mainly be responsible for carrying out data processing and conversion according to the information taken and transmitted by the tracking camera, controlling the robot controller at the same time, and the robot controller accepts the command, directs, and controls the electric spinning robot to use the electrospinning device to complete the command indication. According to the transfer of modified information feedback, the shape of electrospun model and the spinning path are modified timely. Therefore, it overcomes the disadvantage that nanofibers cannot be plasticized and operated flexibly.
A rotating robot multi-nozzle electrospinning device
Conclusion and outlook
Robot-aided electrospinning provides much higher operation precision and stability, which makes the 3D construction of nanofibers possible and allows us to design the nanofiber’s shape according to the actual requirements. Yet, there are still many challenges that need to be addressed to make the truly intelligent biomedical engineering. Firstly, in the electrospinning process, the electrical field is one of the most parameters, which directly determines the fabrication accuracy. However, the current robot-aided electrospinning is mainly focusing the position control, and few is mentioned the dynamic model of the electrical field. More theoretical works in electrical field would be very helpful to establish the model of the electrospinning field. Secondly, the sensing method to monitor the condition of the fabricated fiber is still limited. To control the fabrication process precisely, one important thing is to estimate the product dynamically. However, in current electrospinning system, the only thing can do is to image the structure of the fibers. Other import information, such as the dimeter and mechanical property, has to be investigated after fabrication. Such off-line sensing technique brings big challenges to the real-time robot control. Hence, sensing fusion techniques that are able to get more information of the biofibers in real time could promote the system a lot. Lastly, an effective control strategy for the fabrication process should also be considered. As discussed above, the fabrication process is affected by many factors, such as voltage, nozzle–collector distance, solution, temperature. Considering those factors are coupled together, we shall build a model and design a strategy to adjust those parameters dynamically to achieve the desired result. Unfortunately, up to now, rare related works have been done, and the mechanism behind is still not clear. Therefore, more effort should be taken in this direction.
In summary, the robot-aided electrospinning is an emerging highly interdisciplinary field, which required both the knowledge of robotics and biomedical. In the future, a deep integration of the general electrospinning and the robotic should be a way to address the existing challenges. From the perspective of device design, controllable design extends the concept of “thinner” design, aiming at developing products to apply the various biomedical fields. It is particularly important to develop a simple and high accuracy of robot-aided electrospinning for saving time, simple assembling, disassembling, and maintaining.
RT and XY drafted the manuscript. YS gave comments and ideas about the organization and contents of the article. All authors read and approved the final manuscript.
This work was partly supported by Shenzhen (China) Basic Research Project (JCYJ20160329150236426).
The authors declare that they have no competing interests.
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Any requests for materials should be addressed to Y.S. (email: email@example.com).
This work was partly supported by Shenzhen (China) Basic Research Project (JCYJ20160329150236426, JCYJ20170413140519030).
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