Tunable Spun Fiber Constructs in Biomedicine: Influence of Processing Parameters in the Fibers’ Architecture

In recent years, micro-and nanofibers have emerged as promising tools for biomedical applications for displaying advantageous features, including large surface area, high porosity, and tunable structure, functionality, mechanical performance. Moreover, their high area-volume ratio (relation between width and diameter), capacity to form intricated 3D networks, and ability to incorporate various chemical functions or tune their molecular orientation to improve bioactivity, make them ideal for drug delivery and tissue engineering uses. Polymer physical and chemical properties can be improved during fiber extrusion by ameliorating the alignment of the polymeric chains through the fiber axis. This effect can be achieved via spinning techniques, which are specialized extrusion methods in which a spinneret forms continuous filaments. These techniques involve irreversible processes, in which the solidification of a liquid with a restricted size occurs in two directions. Usually, the goal is to convert the solid polymer in a spinnable solution, either by melting or dissolution in appropriate solvent or by chemically altering the polymer to generate soluble derivatives. The most commonly used spinning methods are the electrospinning, wet-spinning, dry-spinning and melt-spinning.

In the melt-spinning technique, dried polymer granules are melted inside an extruder and used as the spinning dope. Afterwards, the filament is subjected to a fast fiber solidifying process due to a one-way heat transfer. This manufacturing process is preferred amongst many polymers, since no solvents are required. However, there are still several limitations associated with this technique, such as polymer decomposition at temperatures below the melting point, a weak control of the temperature of the polymer melt, and restrictions in the ability to produce fine fibers. Electrospinning resorts to electrostatic forces to induce the formation of fine fibers from polymer solutions. In this process, the polymer solution is ejected through a needle connected to an electric field, which attracts the polymer jet towards a collector. Electrospinning has been gaining considerable attention in biomedicine, due to the versality, simplicity and cost efficiency of the technique.

Further, the resemblance of the electrospun fibers with the organization of the extracellular matrix can contribute to higher proliferation and migration of cells, as well as an improved control of fluid loss. Electrospun fibers can also present high loading and encapsulation efficiency, making them suitable for drug release systems. Still, there are as well some issues associated with the use of these electrospun constructs, mainly the limited cell infiltration throughout the innermost regions of the scaffolds that cannot be ensured via these high fiber packing density and small pore-size constructs and the maintenance of environments that can resemble interstitial fluids. Wet-spinning has arisen as an alternative spinning method for the production of microfiber structures with different levels of organization and tunable chemical and physical properties that can enhance cell infiltration and maturation.

Additionally, wet-spinning overcomes limitations associated with polymer thermal degradation, which tend to be associated with melt-spinning techniques. Wet-spinning is based on the principle of precipitation during which a phase inversion takes place as the polymer solution is extruded through a spinneret into a coagulation bath. Just as the previous techniques, this too presents limitations, particularly related to the type of polymers that can be used and the need for specialized coagulation baths that may raise the cost of production. Another technique that shares many of the wet-spinning principles is the dry-spinning approach. Here, polymer solidification is easy to achieve by the evaporation of a volatile solvent; contrary to wet-spinning, no coagulation bath is necessary. However, this approach can only be employed to polymers that do not generate viscous melts and that can be processed with volatile compounds. It is a frequent choice to extrude polymers vulnerable to thermal degradation.

Among these approaches, electrospinning and wet-spinning are the ones considered most relevant for biomedical uses, particularly for drug delivery systems, since they allow to control fiber production in such a way that complex fiber structures with different organizations and architectures can be attained: (1) side-by-side fibers, (2) porous, (3) helical, (4) core-shell, (5) hollow, (6) tri-axial, (6) multilayered. Such morphologies require a precise control of processing parameters. Indeed, polymer spinnability, as well as the fiber porosity and diameter, are dependent not only on the solution properties (e.g., concentration, polymer nature and viscosity) but as well on the system processing parameters (e.g., injection flow rate, coagulation bath, applied voltage) and environment conditions (e.g., temperature and humidity) In the present work, the relationship between processing parameters and fiber morphology, organization, and architecture are analyzed in great detail. The principles of electrospinning and wet-spinning are here emphasized; however, contrary to previous reviews that focused on uniaxial fibers, special attention is given to complex architectures and their main applications in drug delivery and tissue engineering fields. These fiber constructs are gaining more attention each day and, hence, we are here exposing the reasons behind their selection.