1. Introduction
COVID-19 has contributed to a worldwide healthcare crisis resulting in several hundreds of thousands of deaths over recent years and complications that can lead to severe pneumonia
[1][2]. In synergy with Polymer Engineering, Bioengineering, and Advanced Manufacturing, the mRNA vaccine was successfully developed and blocked the further spread of the virus on a large scale
[3][4]. The mRNA-1273 vaccine approved for use under urgent circumstances has the potential to be unsafe for delivery, being inherently unstable while the large density of negative charges makes it difficult to cross cell membranes
[5][6], and the latest research uses polymer-based composites as carriers for effective vaccine delivery
[7].
In medical applications, polymers with superior biocompatibility are often used to not produce antibody reactions or even stimulate inflammation in contact with the human body
[8][9][10]. Synthetic polymers include: polycaprolactone (PCL), poly (vinyl alcohol) (PVA), polylactide (PLA) and poly (lactic-co-glycolic acid) (PLGA)
[11][12]; natural polymers include: Chitosan (polysaccharide), cellulose (polysaccharide), gelatin (protein), silk proteins (proteins)
[13], etc. In biomedical applications, natural polymers are often perceived as relatively safe, biocompatible and degradable polymers
[14]. Cellulose is a linear polysaccharide, the main component of the cell wall, which is currently the most used in biological applications from bacteria
[15]. Taokaew et al. composite nanofibers based on bacterial cellulose with Garcinia mangostana peel extract exhibited potent bacterial inhibition against Gram-positive bacteria while treating the membranes with MCF-7 breast cancer cells for 48 h, only 5% of the cancer cells remained viable
[16]. The protein class of silk fibroin, unlike other natural polymers, has outstanding elasticity and strength, which is of interest in tissue engineering applications
[17][18].
The advantages of synthetic polymers over natural polymers are their stability, superior mechanical properties and degradability. PCL is an aliphatic semicrystalline polymer with hexanoic acid formed by esterolysis
[19], which can be excreted through the digestive system, thus making it biocompatible, biodegradable, non-toxic and popular in medical applications, such as drug delivery, wound plug dressings and stents. The use of PCL scaffolds for tissue engineering has been reported in detail by Janmohammadi et al.
[20]. Zavan and co-works prepared a bilayer fibrous scaffold with the outer layer of PCL exhibiting the best in vitro response to fibroblasts and weak adhesion to cellular tissues due to the hydrophobicity of PCL to cellular tissues, while the inner layer used gelatin-modified PCL to significantly promote gene expression in endothelial cells
[21].
Nanoscale polymers have a wide range of uses in various fields, especially in medical applications, where the electrospinning process (
Figure 1) is one of the most convenient ways to prepare nanofiber membranes (1–100 nm) directly and continuously
[22][23][24][25][26]. Laboratory electrospinning setup generally has three components: a high voltage electrostatic generator (1–30 kv), a spinning head and a collector (opposite charge target) for the process of producing various continuous nanofiber assemblies with controlled morphology and dimensions from polymer solutions or melts under a high voltage electric field
[27][28][29]. The development of the electrospinning (ES) process was a somewhat difficult journey. In the 16th century, William Gibert discovered a conical droplet formed when charged amber approached water droplets. Micro-droplets are also ejected from the conical droplets. The beginning of electrospinning technology is recognized to be in 1934, when Anton Formalas invented a device to prepare polymer fibers by electrostatic force action, presenting for the first time how a polymer solution could form the jet between electrodes. Subsequent years of intermittent patent publication have not attracted much attention from researchers. In 1990, Reneker’s research team at the Acolon University, USA, went deeper into the electrospinning (ES) process and applications, with ES of various organic polymer solutions into fibers, ES process is rapidly becoming a research hotspot, entering a new era of vigorous development
[30][31].
Figure 1. Schematic diagram of electrospinning setup.
To prepare the desired nanofibers, the electrospinning process usually requires setting parameters, the main influencing factors being the system (nature of the polymer, solution viscosity, conductivity and surface tension)
[32], process parameters (voltage, receiving distance and flow rate)
[33] and environmental factors (temperature and humidity)
[34].
Synthetic polymers have modifiable mechanical properties, but the hydrophobic nature contributes to an absence of cell adhesion and the onset of inflammation, which is usually modified by natural polymers. One problem that most natural polymers suffer from is the deficiency of certain mechanical properties
[35]. To combine the advantages of various polymers and overcome their limitations, the desired properties have been achieved using blends of these polymers instead of using single polymers by optimizing the ratio between the components of the blend. During drug release, the hydrophobic properties of the polymer seriously affect the release performance of the loaded drug. Huo and co-workers used PCL blended with gelatin to effectively improve the hydrophobic properties of the composite fiber. Drug release demonstrated that the increased PCL content made the composite fiber more hydrophobic, which belonged to the slow release of artemisinin (ART) and enhanced the therapeutic effect
[36]. Chen et al. improved the defect of gelatin’s poor hemostasis ability for large wounds by co-mixing sodium alginate, which can form a gel on the wound surface, and achieved hemostasis of rat wounds in only 1.53 min
[37].
Nanofiber membranes are prepared by the ES process of polymers, and the application scenario is constrained to fiber scaffolds
[38][39][40]. Researchers are not satisfied with this single role, so various functional nanofiber membranes have been prepared by ES in combination with multifunctional materials, among which NNHs show great potential to combine the advantages of nanoparticles with the properties of polymers. Additionally, the is a wide range of application scenarios
[38][39][40][41][42][43][44][45]. Of interest is that as with decades of research, the number of electrospun nanoparticle articles published occupies half the number of electrostatic spinning (
Figure 2). It shows the pivotal position of NNHs.
Figure 2. The literature search statistics of “electrostatic spinning” and “electrospun nanoparticles” on the “Web of Science” platform, respectively.
Multiple nanoparticles have been successfully prepared into nanofibers, which mainly include: metal
[46], metal oxide
[47] and polymer nanoparticles (NPs)
[48][49]. The presence of NPs in polymer solution is uniformly dispersed and will be randomly distributed on the surface or inside the nanofibers (NFs). Therefore, the co-blending of NPs with polymer solutions is the most common form. During the process of electrospinning the mixture into fibers, the homogeneity of NPs in the polymer solution and the interfacial interaction between nanoparticles and polymer solution significantly affect the performance of NNHs. To attenuate the effects of the above factors, the NPs can be mixed by physical mixing methods (stirring and sonication), by dissolving the NPs and polymer in different solvents separately or adding a certain amount of surface activator. The electrospun fiber precursor working solution can effectively reduce the phenomenon of nanoparticle agglomeration and even blockage of the spinning heads after mixing uniformly
[50][51][52]. Secondly, other processes combined with ES technology can also effectively load NPs into NFs. For instance, the modification of NFs by plasma technology. This methodology promotes the interaction between NPs and easily loads NPs on the nanofiber surface
[53]. The electrospray
[54] or magnetron sputtering
[55] technology allows the uniform spraying of NPs on the fiber surface. The single-fluid ES process requires mixed solutions with a certain viscosity and dispersion. Otherwise, a non-spinnable or agglomerative phenomenon will occur. Multi-fluid dynamics have been studied for many years. The design of the spinneret is especially important. The morphological structure of the nanofibers is similar to the spinneret structure
[56]. Multi-fluid dynamics ES processes often require only one fluid available for spinning to form nanofibers
[57]. Zheng et al. used TiO
2 suspension as the sheath layer and PEO as the core layer, which perfectly avoided the enrichment of TiO
2NPs using a modified coaxial electrospinning process, and the uniform TiO
2NPs on the nanofiber surface enhanced the absorption of UV light
[58]. The NPs are loaded in nanofibers based on the above single-step process, and if the NPs are not well dispersed in the working solution, many self-assembly strategies are available to grow NPs in the fibers by initiation effects in the precursor solution, including: in situ synthesis
[59], hydrothermal-assistance
[60] and calcination
[61].
NNHs prepared by combining the characteristics of biocompatible polymers and multifunctional nanoparticles are already practical in medical applications
[62][63]. Researchers is to investigate the preparation of nanofiber and nanoparticle hybrids in-depth by combining different processes with ES; concentrate on the most recent breakthroughs of NNHs in the medical area (
Figure 3); and provide clear concepts for research workers in material preparation and application.
Figure 3. Electrospun fiber and NPs structures and their hybrids in medical direction.