1. Introduction

Most of the engineering and practical applications, such as wastewater treatment processes and aerodynamic design problem, often have a multiobjective nature and require solving several conflicting objectives [1–3]. Handling with these multiobjective optimization problems (MOPs), there are always a set of possible solutions which represent the tradeoffs among the objectives known as Pareto-optimal set [4–5]. Evolutionary multiobjective optimization (EMO) algorithms, which are a class of stochastic optimization approaches based on population characteristic, are widely used to solve the MOPs, because a series of Pareto-optimal solutions can be obtained in a single run [6–9]. The multiobjective optimization algorithms are striving to acquire a Paretooptimal set with good diversity and convergence. The most typical EMO algorithms include the

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

non-dominated sorting genetic algorithm (NSGA) [10] and NSGA-II [11], the strength Pareto evolutionary algorithm (SPEA) [12] and SPEA2 [13], the Pareto archived evolutionary strategy (PAES) [14], the Pareto envelope-based selection algorithm (PESA) [15] and PESA-II [16].

parameter mechanism for updating the personalized flight parameters of the mutated particles in [36]. The results show that this flight parameter mechanism performs efficiently in exploring solutions close to the true Pareto front. In the above MOPSO algorithms, the improved strategies are expected to achieve better performance. However, few works have been done to

Motivated by the above review and analysis, in this chapter, an adaptive gradient multiobjective particle swarm optimization (AGMOPSO) algorithm, based on a multiobjective gradient (MOG) method, is put forward. This novel AGMOPSO algorithm has faster convergence in the evolutionary process and higher efficiency to deal with MOPs. The proposed AGMOPSO algorithm contains a major contribution to solve MOPs as follows: A novel MOG method is proposed for updating the archive to improve the convergence speed and the local exploitation in the evolutionary process. Unlike some existing gradient methods for single-objective optimization problems [38–40] and MOPs [41], much less is known about the gradient information of MOPs. One of the key feathers of the MOG strategy is that the utilization of gradient information for MOPs is able to obtain a Pareto set of solutions to approximate the optimal Pareto set. In view of the advantages of the MOG strategy, this AGMOPSO algorithm can obtain a good Pareto set and reach smaller testing error with much faster speed. This characteristic makes this method ideal

A minimize MOP contains several conflicting objectives which is defined as:

ð Þ y ≤ f i

∀i : f i

minimize Fð Þ¼ x f 1ð Þx ; f 2ð Þx ; ⋯; f mð Þx T

where m is the number of objectives, x is the decision variable, fi() is the ith objective function. A decision variable y is said to dominate the decision vector z, defined as y dominates z or

ð Þz and ∃j : f j

where i = 1,2, …, m, j = 1,2, …,m. When there is no solution that can dominate one solution in MOPs, this solution can be used as the Pareto optimal solution. This Pareto optimal solution

PSO is a stochastic optimization algorithm, in which a swarm contains a certain number of particles that the position of each particle can stand for one solution. The position of a particle

,

A Gradient Multiobjective Particle Swarm Optimization http://dx.doi.org/10.5772/intechopen.76306 79

ð Þz , (2)

subject to x∈ Ω, (1)

ð Þ y < f j

examine the convergence of these MOPSO algorithms [37].

for MOPs.

2. Problem formulation

2.1. Multiobjective problems

y≺z, which is indicated as:

comprises the Pareto front.

2.2. Particle swarm optimization

which is expressed by a vector:

The notable characteristic of particle swarm optimization (PSO) is the cooperation among all particles of a swarm which is attracted toward the global best (gBest) in the swarm and its own personal best (pBest), so the PSO have a better global searching ability [17–19]. Among these EMO algorithms, owing to the high convergence speed and ease of implementation, multiobjective particle swarm optimization (MOPSO) algorithms have been widely used [20– 23]. MOPSO can also be applied to multiple difficult optimization problems such as noisy and dynamic problems. However, apart from the archive maintenance, in MOPSO, two issues still remain to be further addressed. The first one is the update of gBest and pBest, because the absolute best solution cannot be selected by the relationship of the non-dominated solutions. Then, the selection of gBest and pBest results in the different flight directions for a particle, which has an important effect on the convergence and diversity of MOPSO [24].

Zheng et al. introduced a novel MOPSO algorithm, which can improve the diversity of the swarm and improve the performance of the evolving particles over some advanced MOPSO algorithms with a comprehensive learning strategy [25]. The experimental results illustrate that the proposed approach performs better than some existing methods on the real-world fire evacuation dataset. In [26], a multiobjective particle swarm optimization with preferencebased sort (MOPSO-PS), in which the user's preference was incorporated into the evolutionary process to determine the relative merits of non-dominated solutions, was developed to choose the suitable gBest and pBest. The results indicate that the user's preference is properly reflected in optimized solutions without any loss of overall solution quality or diversity. Moubayed et al. proposed a MOPSO by incorporating dominance with decomposition (D2MOPSO), which proposes a novel archiving technique that can balance the relationship of the diversity and convergence [27]. The analysis of the comparable experiments demonstrates that the D2MOPSO can handle with a wide range of MOPs efficiently. And some other methods for the update of gBest and pBest can be found in [28–31]. Although many researches have been done, it is still a huge challenge to select the appropriate gBest and pBest with the suitable convergence and diversity [32–33].

The second particular issue of MOPSO is how to own fast convergence speed to the Pareto Front, well known as one of the most typical features of PSO. According to the requirement of the fast convergence for MOPSO, many different strategies have been put forward. In [34], Hu et al. proposed an adaptive parallel cell coordinate system (PCCS) for MOPSO. This PCCS is able to select the gBest solutions and adjust the flight parameters based on the measurements of parallel cell distance, potential and distribution entropy to accelerate the convergence of MOPSO by assessing the evolutionary environment. The comparative results show that the self-adaptive MOPSO is better than the other methods. Li et al. proposed a dynamic MOPSO, in which the number of swarms is adaptively adjusted throughout the search process [35]. The dynamic MOPSO algorithm allocates an appropriate number of swarms to support convergence and diversity criteria. The results show that the performance of the proposed dynamic MOPSO algorithm is competitive in comparison to the selected algorithms on some standard benchmark problems. Daneshyari et al. introduced a cultural framework to design a flight parameter mechanism for updating the personalized flight parameters of the mutated particles in [36]. The results show that this flight parameter mechanism performs efficiently in exploring solutions close to the true Pareto front. In the above MOPSO algorithms, the improved strategies are expected to achieve better performance. However, few works have been done to examine the convergence of these MOPSO algorithms [37].

Motivated by the above review and analysis, in this chapter, an adaptive gradient multiobjective particle swarm optimization (AGMOPSO) algorithm, based on a multiobjective gradient (MOG) method, is put forward. This novel AGMOPSO algorithm has faster convergence in the evolutionary process and higher efficiency to deal with MOPs. The proposed AGMOPSO algorithm contains a major contribution to solve MOPs as follows: A novel MOG method is proposed for updating the archive to improve the convergence speed and the local exploitation in the evolutionary process. Unlike some existing gradient methods for single-objective optimization problems [38–40] and MOPs [41], much less is known about the gradient information of MOPs. One of the key feathers of the MOG strategy is that the utilization of gradient information for MOPs is able to obtain a Pareto set of solutions to approximate the optimal Pareto set. In view of the advantages of the MOG strategy, this AGMOPSO algorithm can obtain a good Pareto set and reach smaller testing error with much faster speed. This characteristic makes this method ideal for MOPs.


**1. Introduction**

According to the estimates of the International Energy Agency (IEA), almost a fifth of all consumed electricity in the world is spent on lighting. One way to reduce the proportion of consumed electricity and its economical expenditure is the development of new energy-efficient light sources and lighting devices based on them. Requirements for such light sources are

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

dictated by market demands, as well as the development and capabilities of modern technologies. Modern light sources must satisfy a number of parameters, combining high light output and efficiency with the comfort of perceiving generated radiation by the eye (a wide spectrum of radiation and color rendering), durability and environmental friendliness with low cost and a wide range of applications.

were conducted in Europe by Plasma International Group [2]. In 2010, the lighting system AS1300 was presented, consisting of a power supply, a microwave generator (magnetron) and the light module. However, their production was complicated by the complexity of the

Microwave Energy and Light Energy Transformation: Methods, Schemes and Designs

http://dx.doi.org/10.5772/intechopen.73755

77

Recently, there have been designs of relatively low-power plasma lighting devices based on light emitting plasma (LEP) lamps with power from ~160 W to 300–400 W, in which solid-state microwave generators are used as an electromagnetic field source [3]. Now, the scope of such lamps is growing: from architectural lighting and street lighting to their application in the

The peculiarity of the topic of plasma light sources with microwave excitation is the long and constant interest to them (more than 25 years), which is expressed in a great number of scientific publications, including monographs, articles, patents obtained in different countries of the world. What is the heightened interest to the lighting systems based on plasma lamps with microwave excitation in? The answer to this question lies in the unique combination of their technical and lighting characteristics and parameters that most fully meet the requirements for light sources formulated above. For example, light generated by these lamps is characterized by high light flux (120–145 klm), light intensity (~9000 cd) and brightness, as well as good light output (80–110 Lm/W). Technical parameters of lighting devices based on plasma light sources with microwave excitation are characterized by relatively low power consumption, a continuous spectrum close to natural (solar) illumination with a color coefficient *R a* > 90 (with a maximum value of 100) and the ability to control the intensity of light. An important advantage is also their environmental friendliness, which is due to the lack of mercury and the use of environmentally friendly materials—argon and

Among the problems that need to be addressed, we should note the insufficiently long service life of magnetrons and the uneven heating of the surface of the lamp bulb, which requires to provide its rotation in the cavity space as well as studies aimed at selecting new materials. This will increase the durability of the lamp, which today does not exceed ~50 thousand

This chapter is organized in five main sections. Section 1 describes the construction of a lighting device based on an electrodeless sulfur lamp with microwave excitation, gives a brief characteristic of its main components and analyzes their operation parameters. Section 2 considers an application of the electrodeless sulfur lamps with microwave excitation as the simulators of solar radiation, gives the comparative characteristics of such lamps with other lighting sources. Section 3 concerns promising directions for practical application of a lighting installation based on an electrodeless sulfur lamp with microwave excitation, in particular, for using in greenhouses. Section 4 presents the construction of the lighting system with the possibility of regenerating the energy of optical radiation into direct current energy for increasing its full efficiency. The main conclusions

design and the high cost of the lighting device.

automobile industry.

sulfur.

hours.

are formulated in Section 5.

It is known that the problem of lighting is being solved by converting electrical energy into optical energy (visible light) with the help of various media and the processes occurring in them: metals and thermal processes (incandescent lamps (IL)), gaseous media and discharge (including plasma) phenomena (fluorescent (FL) and metal halide (MHL) lamps, etc.), as well as semiconductor materials and processes of spontaneous recombination of injected minority carriers (light-emitting diodes (LEDs)). Comparative efficiency of existing light sources is shown in **Figure 1**. It can be seen that the heat sources of light (incandescent lamps) in view of their low efficiency (only 3% of the supplied electric energy is converted into the energy of light waves) are much inferior to discharge lamps and LEDs.

Among the existing promising sources of light, special attention is paid to the development of plasma lighting devices based on the use of an electrodeless sulfur lamp with microwave excitation (ESLME). For the first time, such kind of lamp was presented in 1992 at the VI International Symposium on the Science and Technology of Light Sources in Budapest [1]. Later, based on it, Fusion Lighting Co. company created the lighting system Solar 1000 (1994), as well as its modification Light-drive 1000 (1997). Significant efforts to expand the use of these lamps were made by the Korean company LG Electronics, which, in 2005, held a presentation of the plasma lamp Plasma Lighting System (PLS), and also organized a series production of a number of designs of such light sources in the form of a ceiling lamp and spotlight lamp. In parallel, studies of electrodeless sulfur lamp with microwave excitation

**Figure 1.** Evaluation of the effectiveness of light sources.

were conducted in Europe by Plasma International Group [2]. In 2010, the lighting system AS1300 was presented, consisting of a power supply, a microwave generator (magnetron) and the light module. However, their production was complicated by the complexity of the design and the high cost of the lighting device.

dictated by market demands, as well as the development and capabilities of modern technologies. Modern light sources must satisfy a number of parameters, combining high light output and efficiency with the comfort of perceiving generated radiation by the eye (a wide spectrum of radiation and color rendering), durability and environmental friendliness with low cost

It is known that the problem of lighting is being solved by converting electrical energy into optical energy (visible light) with the help of various media and the processes occurring in them: metals and thermal processes (incandescent lamps (IL)), gaseous media and discharge (including plasma) phenomena (fluorescent (FL) and metal halide (MHL) lamps, etc.), as well as semiconductor materials and processes of spontaneous recombination of injected minority carriers (light-emitting diodes (LEDs)). Comparative efficiency of existing light sources is shown in **Figure 1**. It can be seen that the heat sources of light (incandescent lamps) in view of their low efficiency (only 3% of the supplied electric energy is converted into the energy of

Among the existing promising sources of light, special attention is paid to the development of plasma lighting devices based on the use of an electrodeless sulfur lamp with microwave excitation (ESLME). For the first time, such kind of lamp was presented in 1992 at the VI International Symposium on the Science and Technology of Light Sources in Budapest [1]. Later, based on it, Fusion Lighting Co. company created the lighting system Solar 1000 (1994), as well as its modification Light-drive 1000 (1997). Significant efforts to expand the use of these lamps were made by the Korean company LG Electronics, which, in 2005, held a presentation of the plasma lamp Plasma Lighting System (PLS), and also organized a series production of a number of designs of such light sources in the form of a ceiling lamp and spotlight lamp. In parallel, studies of electrodeless sulfur lamp with microwave excitation

and a wide range of applications.

light waves) are much inferior to discharge lamps and LEDs.

76 Emerging Microwave Technologies in Industrial, Agricultural, Medical and Food Processing

**Figure 1.** Evaluation of the effectiveness of light sources.

Recently, there have been designs of relatively low-power plasma lighting devices based on light emitting plasma (LEP) lamps with power from ~160 W to 300–400 W, in which solid-state microwave generators are used as an electromagnetic field source [3]. Now, the scope of such lamps is growing: from architectural lighting and street lighting to their application in the automobile industry.

The peculiarity of the topic of plasma light sources with microwave excitation is the long and constant interest to them (more than 25 years), which is expressed in a great number of scientific publications, including monographs, articles, patents obtained in different countries of the world. What is the heightened interest to the lighting systems based on plasma lamps with microwave excitation in? The answer to this question lies in the unique combination of their technical and lighting characteristics and parameters that most fully meet the requirements for light sources formulated above. For example, light generated by these lamps is characterized by high light flux (120–145 klm), light intensity (~9000 cd) and brightness, as well as good light output (80–110 Lm/W). Technical parameters of lighting devices based on plasma light sources with microwave excitation are characterized by relatively low power consumption, a continuous spectrum close to natural (solar) illumination with a color coefficient *R a* > 90 (with a maximum value of 100) and the ability to control the intensity of light. An important advantage is also their environmental friendliness, which is due to the lack of mercury and the use of environmentally friendly materials—argon and sulfur.

Among the problems that need to be addressed, we should note the insufficiently long service life of magnetrons and the uneven heating of the surface of the lamp bulb, which requires to provide its rotation in the cavity space as well as studies aimed at selecting new materials. This will increase the durability of the lamp, which today does not exceed ~50 thousand hours.

This chapter is organized in five main sections. Section 1 describes the construction of a lighting device based on an electrodeless sulfur lamp with microwave excitation, gives a brief characteristic of its main components and analyzes their operation parameters. Section 2 considers an application of the electrodeless sulfur lamps with microwave excitation as the simulators of solar radiation, gives the comparative characteristics of such lamps with other lighting sources. Section 3 concerns promising directions for practical application of a lighting installation based on an electrodeless sulfur lamp with microwave excitation, in particular, for using in greenhouses. Section 4 presents the construction of the lighting system with the possibility of regenerating the energy of optical radiation into direct current energy for increasing its full efficiency. The main conclusions are formulated in Section 5.


**2.3. Arc welding processes**

Manufacturing information, such as the sequence of operations, lot size; multiple process plans were given special consideration in their approach to solve the generalized part family formation problem. Many authors also point out that the method of artificial neural networks is flexible and can be efficiently integrated with other manufacturing functions. Below, from the literature, some important artificial intelligence applications to particular production processes are described.

• Robot scheduling Yih et al. [59]

Author Ref. num. Moon and Chi [53]

[54] Lee et al. [55] Moon [56] Wu [57]

Wu [57]

Kaparthi and Suresh

Cook and Shannon [58]

Chryssolouris et al. [60]

Injection moulding processes are characterized by dynamic characteristics since process input variables are the melting temperatures, the velocity of the cylinder, the holding, the pressure that produces the polymer flow into the model cavity and they vary in a complex manner. The phenomena occurring in the process are very complex, time-varying, nonlinear and uncertain. This complexity makes it difficult to relate the input operating variables to the product quality such as geometry accuracy and geometry surface smoothness. These processes have been implemented and optimized with the use of artificial intelligence with the use of *multilayer perceptron* which is found to be the most popular network and tries to model the process

In gas metal arc (GMA) welding processes [10–12], the flow of an electric current is generated by an electric arc that is maintained between the consumable wire electrode and the welding

Both the filling metal and the consumable electrode are automatically fed by a wire feeding device. A good quality of the welds is determined by the relatively high depth to width ratio of the molten welding pool. So, the monitoring and control of weld geometry and the surface temperatures that are strongly related with the formation of the weld pool, are very important for the penetration depth or the back bead width. For this purpose, the temperatures by noncontact were measured. Infrared temperature sensing system and recent studies conducted the ANN multilayer perceptron to detect and control with great success all the surface temperature information.

**2.1. Injection moulding processes**

**Category Manufacturing**

204 Advanced Applications for Artificial Neural Networks

Application topic • Manufacturing system

**Table 1.** Summary of neural network manufacturing applications.

design

control

decision

• Manufacturing process

• Manufacturing operational

**2.2. Gas metal arc welding processes**

metal as shown in **Figure 2**.

dynamics and based on this to predict the part quality [3–9].

The complexity of the relationship between the process variable and weld quality is the common factor in all manufacturing processes and in particular arc welding processes. For these reasons, the literature documents with some interesting researches, the use of ANNs for quality monitoring and control of the process. In this type of welding process, the ANN input data are generally the surface temperature, the welding voltage and the current and torch speed. The majority type of ANN employed for this case was, again, the multilayer perceptron [10, 13–21]. Their use was found to be very satisfactory to predict the weld defects, the geometry such as bead width, head height and penetration.

#### **2.4. Machining processes**

To perform a correct quality control in all machining systems, it is very important to check particular parameters such as the cutting tool state, the vibrations, the forces and the temperature obtained during real-time machining operation. To optimize this particular type of supervision of the cutting tool state, some authors document in literature the use of the ANNs which used the above-mentioned process data to classify the status of tool wear, prediction tool life and detect tool failure in an on-line manner. Examples of typical sensors are tool dynamometers, acoustic emission sensor accelerometers and thermocouples. In this process, the networks in frequent use are the multilayer perceptron and Kohonen [22–46].

#### **2.5. Semiconductor manufacturing processes**

The complexity of plasma etching processes in integrated circuits fabrication promoted the use of ANNs for monitoring and control. In this field, the use of artificial intelligence brings advantages that could not be achieved with traditional open loop controls. Where used the multilayer perceptron networks that are the most popular for this process. The ANNs use the fundamental parameters that affecting process dynamics, such as power, gas flow rate, dc bias voltage and throttle positioning. Proper use of networks in this field allows real-time monitoring and estimation of quality variables such as the etching thickness and the etching time [47–52].


**5. Acknowledgment**

This work was financially supported in part by the European Commission in the projects GOSSAMER and PULLNANO, and by the Federal Ministry of Education and Research of the Federal Republic of Germany (project nos. 01M3167 A and 01M3171 A).

The authors would like to express their gratitude to the whole flash development team of the former company Qimonda, especially Tim Höhr for the capacitance simulations.


**6. Conclusions**

Rising concerns over depletion of fossil reserves and the drive towards sustainable and responsible consumption of resources have presented a challenge and opportunity for scientist and engineers to work together in developing methods, technologies and processes for producing of bio-based products. These include commodity chemicals, fuels and materials of which many of the chemicals have solvent properties. As such, they have been widely used in extractions and in solvating a range of physiochemical processes and numerous consumer goods (by either dissolving, stabilizing or modifying the latter's properties) across the manufacturing research and development landscapes. This review has contextualized and discussed some existing and emerging approaches in these areas.

Even though most bio-solvents are still volatile like their petroleum counterparts, the bio-solvents have the advantage of being biodegradable, derived from renewable resources, and their production often results in CO2 emission savings. A novel array of ionic liquids and deep eutectic solvents based on inexpensive bio-derived components has been developed, and because these solvents have low volatility, it presents a solution to the volatile organic solvent concern. Additionally, they are usually recyclable after use, with the benefit of tunability to bring about smart solvents for tailored applications.

**17**

**Author details**

South Africa

*Bio-Solvents: Synthesis, Industrial Production and Applications*

The authors declare no conflicts of interest.

Novisi K. Oklu, Leah C. Matsinha and Banothile C.E. Makhubela\*

\*Address all correspondence to<EMAIL_ADDRESS>
provided the original work is properly cited.

Department of Chemical Sciences, University of Johannesburg, Johannesburg,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

This work was supported by the Royal Society and African Academy of Sciences, the Future Leaders—African Independent Researchers (FLAIR) Scheme (Fellowship ref.: 191779), the National Research Foundation (NRF) of South Africa (Grant numbers: 105559, 112809 and 117989) and the University of Johannesburg's

*DOI: http://dx.doi.org/10.5772/intechopen.86502*

Centre for Synthesis and Catalysis.

**Acknowledgements**

**Conflict of interest**


*5.3. Growth Factor*

Growth factors are naturally occurring endogenous signaling molecules (i.e., proteins or steroid hormones) which are efficient for inciting cellular development, differentiation, regeneration and proliferation by binding to cellular receptors. Recently, marked progress has been made in preparing several types of ultrathin electrospun nanofiber scaffolds to successfully load and deliver several growth factors (Figure 6a) as well as regenerative medicines, owing to the unique characteristics of nanofibers such as large surface area, porous formation, high loading capacity, easy access, and cost-effectiveness [133]. Notably, the large surface area to volume ratio of electrospun nanofibers facilitates cell adhesion, loading, storage and release of growth factors [134]. Those parameters are required for guiding cellular behaviors and transmitting signals that regulate proliferation, differentiation, metabolism, and apoptosis of cells, including extracellular matrix deposition in tissue engineering.

The quick inactivation and very short biological half-life of growth factors are the most important factors hindering their effectual delivery. In addition, it has been noted that the growth factors' carrier should have slow and sequential releasing properties. The establishment of growth factors into nanofiber scaffolds play very crucial roles in repairing and regenerating damaged tissues by mimicking signal transduction from cell to cell, or from cell to its extracellular matrix [135]. Either electrospinning procedures alone (for example, bending, emulsion, and coaxial electrospinning) or in combination with other traditional methods such as hydrogel (electrospinning) are ranked at the top among all nanofiber fabrication techniques for their controlled and sustained release properties. On the other hand, surface modified nanofibers promote high loading efficiency, protection of incorporated growth factors and the binding of growth factors to cell receptors. Those surface modified nanofibers exhibit biochemical and morphological uniformity to natural tissues.

Recently, the polysaccharide matrix is being used as a superior nanofiber material to fabricate a growth factor carrier owing to their low toxicity, biocompatibility, and extracellular matrix mimicking capability. However, introducing the sulfation state to the alginate scaffolds ensures the appointed binding and loading of growth factor into the polymer backbone, as well as maintenance of its control release properties. For instance, Mohammadi S, et al. fabricated electrospun scaffolds by blending alginate sulfate and polyvinyl alcohol to load and deliver transforming growth factor-beta1 (TGF-β1) for tissue engineering applications. For the first time, this research revealed that more successful binding, encapsulation and sustain release of heparin-like proteins from electrospun scaffolds could be achieved by the addition of an affinity site to the alginate [134]. A part of mammalian polysaccharides—glycosaminoglycans (heparin-like substance)—would be another example of an excellent nanofiber matrix because of its efficiency in conjugating with GFs by successfully interacting with its (GFs) anionic sulfated backbones and mimicking a pathway similar to ECM.

**Figure 6.** Schematic of the synthesis of growth factor loaded electrospun nanofiber with the controlled release properties (**a**), and VEGF (vascular endothelial growth factor) release profile with respect to time from PCL nanofibers (Reproduced from ref no [123] with permission from ACS Publications, 2018) (**b**).

Usually, the traditional nanofiber scaffolds-based GFs delivery methods such as dip coating and covalent binding are associated with low entrapment efficiency and primary burst release properties. Currently, researchers are looking for new, innovative and stable strategies by focusing on controlled and sustained release properties. To control the release properties of encapsulated GFs, the usage of gelatin particles in nanofiber fabrication is becoming popular. Generally, the in vitro degradation time of gelatin particles is about 240 h, so researchers tend to use gelatin particle-mediated nanofiber scaffolds as a promising GF nanocarrier. The basic advantages of using gelatin particles are their slow degradation and controlled release properties in a biological environment because of

introducing cross-linking treatment during fabrication. An example would be the work of Jiang and co-workers who prepared PCL fibrous scaffolds containing vascular endothelial growth factor (VEGF)-incorporated gelatin particles which were able to exhibit both diffusion and degradation mediated release for a long period of time (Figure 6b), differentiate mesenchymal stem cells from endothelial cells, sustain the durability of the tubular composition, and form new blood vessels among endothelial cells [136]. The integration of various sustained release characteristics within nanofiber scaffolds protects the encapsulated GFs from biological degradation, generates cellular signal transduction as well as repairs and regenerates damage.

Biocompatible and biodegradable polymeric nanoparticles and biomimetic hydrogel have gained more attention for encapsulating various types of growth factors and confirming their controlled and prolonged releasing [133]. VEGF and bone morphogenetic protein 2 (BMP2) were incorporated and injected to improve the angiogenesis and regeneration of bone in rabbits [133]. Another preclinical study suggested that VEGF-loaded and hMSC (human bone marrow stroma cells)-seeded PDLA nanofiber scaffolds are able to regenerate blood vessels and enhance bone growth [137]. Interestingly, to achieve dual actions from two separate GFs at a time, core/shell nanofibers or emulsion electrospinning methods are widely used in tissue engineering applications. Liu et al. prepared bicomponent scaffolds with the emulsion electrospinning method for delivering two GFs at the same time in nerve tissue engineering. In this study, the nerve growth factor was encapsulated in poly(D,L-lactic acid) (PDLLA) nanofiber scaffolds whereas the glial cell line-derived neurotrophic factor was incorporated in poly(lactic-co-glycolic acid) (PLGA) electrospun scaffolds [138]. This dual factor core/shell electrospun nanofiber scaffold not only revealed its sustained release and degradation-dependent weight loss properties over 42 days but also ensured the high entrapment efficiency and the intact bioactivity of GFs. Apart from degradation-based controlled release behavior of electrospun scaffolds, providing the affinity sites and/or covalent binding of heparin to the surface of nanofibers is also established. The covalent binding of heparin-like proteoglycans on the surface of the nanofibers preserves the biological integrity of GFs and promotes the sustained release properties of the scaffolds. The aminated PLGA was immobilized with VEGF in the presence of heparin via EDC/NHS coupling to facilitate the sustained release properties of the encapsulated growth factor [139]. The presence of hydroxyl (–OH) and carboxylic acid (–COOH) groups on the surface of the heparin simplifies its modification with both GFs and nanofiber scaffolds. Heparin also increased the binding capacity of VEGF to VEGF receptors on the cell surface.

The time period of sustained release of GFs from its carrier should be proportional to the time period of GFs capability to preserve the nanofiber scaffolds; therefore, this important factor is considered during the design of nanofiber-mediated GFs delivery. Employing several electrospinning techniques, the preservation of GFs' bioactivity is achieved for the proliferation and migration of specific cells. The heterogeneous electrospun matrix made of biocompatible poly(L-lactide-co-caprolactone) and poly(2-ethyl-2-oxazoline) was able to protect the bioactivity of dual angiogenic basic fibroblast growth factor and vascular endothelial growth factor during and after their physical blending. It is also capable of mimicking the topography and chemical cues of native cardiac tissue structures [140]. The structural integrity and bioactivity of encapsulated GFs remained the same over the total period of sustained release in comparison with the pure GFs. In another study, for the first time, Naskar et al. reported the anteriority of using natural polymer silk protein fibroin reinforced synthetic carbon nanofiber scaffolds for preserving bioactivity and controlling the sustained release kinetics of BMP-2 and TGF-β1 GFs over a prolonged period of 50 days [141]. The primary attachment of GFs and the regeneration, excess proliferation, and differentiation of both osteoblastic cells and MSC proved the structural integrity of encapsulated GFs in the nanofiber scaffolds. Moreover, a few linear polysaccharides (i.e., chitosan) are very popular for encapsulating GFs (transforming growth factor beta-1). The major challenge associated with the polysaccharide-based GFs delivery system is their short biological half-life. Hence, they are further composited with nanofiber scaffolds in order to improve the long term presence of GFs in stem cells through maintaining their

sustained release from electrospun scaffolds [142]. Previously reported data proved the efficiency of electrospinning methods to load and achieve the sustained release properties of two different GFs at the same time in tissue engineering applications, but now it is also possible to accomplish the distinct release kinetics and spatiotemporal delivery of two different GFs from the same scaffolds with various layered configurations by applying several electrospinning techniques. The combination of emulsion, sequential, high speed and double-sourced double power electrospinning were employed to fabricate tri and tetra layered nanofiber scaffolds using poly(lactic-co-glycolic acid) and poly(D,L-lactic acid) [135]. This glial cell line-derived growth factor and nerve growth factor incorporated multilayer electrospun nanofibers was able to maintain various release actions of these GFs due to aligned fiber coating in each layer with a controlled thickness. The cumulative release studies of encapsulated-GFs indicated distinct release properties from different sites of tri-layered and tetra-layered nanofiber scaffolds over a period of 42 days.