The Role of Biomaterials in Treating Peripheral Nerve Injury
Peripheral nerve injury (PNI) remains a significant medical challenge due to its slow recovery process and complex clinical outcomes. When a nerve is damaged, prolonged denervation can lead to muscle atrophy and reduced Schwann cell activity, both critical for axonal regeneration. In response, innovative approaches such as biomaterial-based implants have emerged as promising solutions to accelerate nerve recovery.
While drugs like ibuprofen have shown potential in promoting nerve regeneration through anti-inflammatory properties, systemic administration often causes unwanted side effects. To overcome this, electrospinning in the biomedical field has gained traction as a method for delivering drugs directly to the injury site via polymer-based scaffolds. Recently, the University College London School of Pharmacy published a study in which the team developed ibuprofen-loaded electrospun materials suitable for surgical implantation in peripheral nerve injuries using our Fluidnatek LE-50 G2 equipment.
What is Electrospinning and Why is it Ideal for Nerve Recovery?
Electrospinning is a versatile technique that transforms polymer solutions into fine, nano- to micro-scale fibers by applying a high-voltage electric field. These fibers are collected into mats that mimic the extracellular matrix of tissues, making them ideal candidates for biomedical applications, especially in nerve repair.
The advantages of electrospun materials include:
Customizability: Physical properties like mechanical strength and drug release rates can be tuned.
Biocompatibility: Synthetic polymers such as polycaprolactone (PCL) and polylactic acid (PLA) are widely used due to their compatibility with biological systems.
Sustained Drug Release: Electrospun fibers can encapsulate drugs like ibuprofen, ensuring controlled and prolonged release at the target site.
For peripheral nerve injury, electrospun wraps or implants loaded with therapeutic agents significantly enhance the healing process by delivering localized treatment, minimizing side effects.
Electrospinning and Ibuprofen Delivery for Nerve Recovery
Recent advancements have demonstrated the successful development of ibuprofen-loaded electrospun biomaterials for peripheral nerve injury. Ibuprofen, a widely used non-steroidal anti-inflammatory drug (NSAID), is known to improve nerve regeneration by inhibiting inflammatory responses and promoting neurite growth.
In a cutting-edge study, researchers optimized the use of electrospun nerve wraps fabricated from PCL, PLA, and their copolymers. The following findings underscore the potential of these polymer-based implants:
Optimized Fiber Properties: Electrospinning parameters were tuned to produce smooth, defect-free fibers with varying diameters. The incorporation of ibuprofen into these fibers allowed for a controlled, sustained release over 21 days.
Surgical Handling: User evaluations highlighted the importance of mechanical properties, with PLA/PCL (70/30) blends demonstrating superior flexibility and strength, making them ideal for nerve-wrapping applications.
In Vivo Performance: In animal models, ibuprofen-loaded electrospun materials accelerated nerve regeneration. Axon counts in treated nerves were significantly higher compared to controls, confirming the therapeutic effect of localized ibuprofen delivery.
Photographs showing stages of electrospun material implantation procedure in a rat sciatic nerve crush model.
Polymer Selection in Electrospinning for Biomedical Implants
The success of electrospun biomaterials depends heavily on the choice of polymers. For peripheral nerve injury, polymers must exhibit biocompatibility, biodegradability, and mechanical stability. The following polymers are commonly employed:
Polylactic Acid (PLA): Known for its slow degradation rate, PLA provides a robust structure but can be brittle.
Polycaprolactone (PCL): Offers excellent flexibility and strength, ideal for implants requiring pliability.
PLA/PCL Copolymers: Combining the strengths of PLA and PCL, these copolymers achieve the desired balance of mechanical stability and handling ease.
In the case of ibuprofen-loaded electrospun implants, PLA/PCL (70/30) was identified as the most suitable formulation due to its superior surgical handling and sustained drug release profile.
Summary of formulation properties. Scanning electron micrographs (A) reveal cylindrical fibres with no visible defects. A histogram of fibre diameters (B) shows unimodal distribution for all tested formulations. Cumulative ibuprofen release data (C) present an initial burst release followed by a period of sustained release over 21 days (Each formulation was tested in triplicate, and the results are presented as mean ± SEM (n = 3)).
The Future of Electrospun Biomaterials in Nerve Repair
As research in the biomedical field advances, electrospinning continues to demonstrate immense potential for improving outcomes in nerve injuries. Key areas of future development include:
Scalable Manufacturing: Ensuring that electrospun materials can be mass-produced for clinical use.
Advanced Drug Loading: Incorporating multiple therapeutic agents for synergistic effects on nerve regeneration.
Clinical Trials: Translating promising in vivo results into human applications to validate the efficacy and safety of electrospun biomaterials.
Conclusion
The use of electrospinning in the biomedical field has revolutionized the development of drug-loaded implants for peripheral nerve injury. By leveraging polymers such as PLA and PCL, researchers have created biomaterials capable of delivering sustained, localized treatment, accelerating nerve regeneration and functional recovery.
Ibuprofen-loaded electrospun fibers represent a significant advancement in nerve recovery strategies, offering a targeted, effective, and minimally invasive solution. As the field continues to evolve, these innovative biomaterials hold the promise of transforming peripheral nerve injury treatment and enhancing patient outcomes.
References
Karolina Dziemidowicz, Simon C. Kellaway, Owein Guillemot-Legris, Omar Matar, Rita Pereira Trindade, Victoria H. Roberton, Melissa L.D. Rayner, Gareth R. Williams, James B. Phillips,
Development of ibuprofen-loaded electrospun materials suitable for surgical implantation in peripheral nerve injury,
Biomaterials Advances,
Volume 154, 2023, 213623,
ISSN 2772-9508,
*All images in the article are the property of the authors.
Why Environmental Control Is Crucial in Electrospinning
The Environmental Control Unit (ECU) is a self-contained external system that supplies conditioned, clean air to the fabrication chamber, regulating temperature (T) and relative humidity (RH) throughout the electrospinning process. Additionally, the air flow can be monitored and adjusted as needed. Properly controlling T, RH, and air flow is essential for achieving consistent fiber or particle morphology, enhancing sample uniformity and production efficiency, and ensuring effective evaporation of solvent vapors—thereby reducing residual solvent in fibers or particles.
Enviromental Control Unit by Fluidnatek.
Achieving reproducible fabrication of nanofibers and nanoparticles by electrospinning and electrospraying can present challenges. Incorporating the ECU significantly boosts the performance of electrospinners by allowing consistent fabrication regardless of time and location and by reducing the risk of clogging. Effective environmental control in electrospinning opens up possibilities for using a broader range of polymers and solvents in advanced sample development. The ECU also enhances the process’s repeatability (ensuring batch-to-batch consistency) and scalability while maintaining safe conditions for the operator.
Advantages of using the Environmental Control Unit developed by Fluidnatek in your electrospinning process when it comes to:
Polymers
Solvents
ACTIVE INGREDIENTS
Fiber properties& Morphology
Scalability
Safety
POLYMERS
Polymers sensitive to temperature & relative humidity:
The ability to control the environmental conditions during electrospinning process expands the list of polymers that can be properly processed. These include polymers particularly sensitive to temperature and humidity. A good example of this, amongst others, are the following polymers: Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA), polylactic-co-glycolic acid (PLGA), polyethylene oxide (PEO), polyacrylonitrile (PAN), polyurethane (PU), Gelatin (Gel), Collagen (Clg), and nylon (N6 or N66). These polymers are used in applications like tissue engineering, medical devices, drug delivery, filtration, energy storage, food packaging, and other ones.
Tightly controlling temperature, relative humidity and air flow will allow consistent Taylor cone stability, prevent needle clogging (in needle-based electrospinning systems), and open research and production possibilities resulting in consistent and reproducible fabrication independent of time of year and location.
Picture 1 demonstrates the impact of precise control over temperature and relative humidity on fiber morphology, showing SEM images of two defect-free samples produced using different environmental conditions.
Figure 1a
Figure 1b
Picture1. Electrospun fibers developed under tight conditions with the Fluidnatek Environmental Control Unit (ECU) technology: a) PCL microfibers at 24°C/40% RH, b) PLA sub-microfibers at 25°C/30% RH. Images by Nanoscience Instruments.
Polymers with High Solvent Affinity:
Polymers that have good affinity to solvents can be difficult to minimize the residual solvent unless the right temperature, relative humidity and sometimes even a specific air flow rate are used during fabrication. A few examples of this include Collagen (Clg), Gelatin (Gel), Chitosan (natural materials) and solvents like Hexafluoroisopropanol (HFIP). These natural polymers are widely used in electrospinning, in uses like tissue engineering applications and medical devices (e.g. in applications like wound healing) as they are found in the native extracellular matrix and can be tuned to application needs thanks to the unique capabilities of electrospinning.
The addition of the Fluidnatek Environmental Control Unit ensures a wide range of temperature and relative humidity, simplifying the processing of polymers and solvents with good affinity and ensuring proper solvent removal during sample development (e.g. R&D stage), or during fabrication, when the process has been scaled up and taken to manufacturing stage.
Figure 2 shows the collagen and gelatin fibers processed with HFIP under tight environmental conditions which can be achieved using the Fluidnatek ECU. Operating at low relative humidities can cause needle clogging and dripping. Preventing needle clogging and dripping was possible for collagen when increasing the humidity up to 63%, allowing for constant electrospun fiber production (Picture 2a).
In the other case, gelatin microfibers from a recipe with HFIP blended with acetic acid as solvents in this electrospinning process, were obtained at lower humidity (35% RH). In this case, the solution and processing parameters were optimized to allow for ribbon shaped structures (Foto 2b).
Figure 2a
Figure 2b
Figure 2. Electrospun natural fibers produced at defined environmental conditions. a) Collagen fibers at 22°C and 63% RH, b) Gelatin fibers at 25°C and 35% RH, both dissolved in HFIP. Images by Nanoscience Instruments.
ENVIRONmental Control in electrospinning with fluidnatek ecu
Solvents
Managing environmental conditions during electrospinning expands the range of usable solvents.
Volatile Solvents:
Solvents like acetone (Ace), dichloromethane (DCM), chloroform (CHF), methyl acetate (MA), and ethyl acetate (EA) are frequently used in electrospinning and electrospraying. With high vapor pressures and rapid evaporation rates, can cause issues such as needle clogging or secondary jetting (Figure 3a), which makes consistent production and reproducibility difficult. Effective environmental control allows these volatile solvents to be used by setting optimal conditions to prevent needle clogging (Figure 3b).
Image 3. Images by Nanoscience Instruments.
Figure 3: A polymer solution with a low boiling point processed at varying humidity levels: a) 25°C, 35% RH causing clogging, and b) optimized at 25°C, 50% RH, allowing for a stable process and preventing clogging. Images by Nanoscience Instruments.
Figure 4 shows typical examples of PCL and PLA fibers and particles developed with high vapor pressure, volatile solvents. These biocompatible materials are widely used in fields such as tissue engineering, medical devices, and drug delivery. Without proper control over temperature and humidity, consistently producing these fibers or particles would not be feasible.
Figure 4a
Figure 4b
Figure 4c
Figure 4. Electrospun fibers and electrosprayed particles produced using highly volatile solvents under controlled environmental conditions: a) PCL in DCM at 25°C, 40% RH, b) PLA in DCM at 25°C, 50% RH, and c) PCL in MA at 22°C, 60% RH. Images by Nanoscience Instruments.
Non-volatile solvents (low evaporation rate):
Solvents with low evaporation rates, such as acetic acid (AA), dimethylformamide (DMF), dimethyl acetamide (DMAc), water (W), and N-Methyl-2-pyrrolidone (NMP), can be challenging to process because they do not evaporate fully, leading to fiber or particle adhesion and significant residual solvent content. This issue commonly arises with these types of solvents. How does the Environmental Control Unit address this challenge? By increasing the air temperature in the chamber (reducing relative humidity) and lowering absolute humidity, the unit facilitates processing and minimizes residual solvent in the resulting fibers or particles.
The water-soluble polymer polyethylene oxide (PEO) is often used in electrospinning as a sacrificial polymer, helping to produce fibers and particles from materials that are otherwise difficult or impossible to spin on their own. Figure 5a displays SEM images of PEO fibers dissolved in water. At low relative humidity, water evaporates more efficiently, enabling larger fiber formation. In contrast, higher relative humidity slows down evaporation, allowing for fine adjustments in microstructure to produce smaller fiber diameters.
Figure 5a
Figure 5b
Figure 5c
Photo 5. Electrospun synthetic polymers dissolved in low vapor pressure solvents under precise environmental conditions with the Fluidnatek Environmental Control Unit: a) PEO in water at 28°C, 40% RH, b) PAN in DMF at 25°C, 40% RH, and c) Thermoplastic polyurethane (TPU) in DMAc at 24°C, 43% RH. Images by Nanoscience Instruments.
Polyacrylonitrile (PAN) is often used in air filtration and as a precursor to carbon nanofibers (which can be produced through calcination) for energy storage applications like fuel cells, where membranes and separators require high energy density. Figure 5b shows PAN fibers produced in DMF, with temperature and humidity optimized to maximize production, reduce fiber bonding, and minimize residual solvent. PAN is highly sensitive to environmental conditions, so a stable Environmental Control Unit like Fluidnatek’s is essential for optimal results.
Thermoplastic Polyurethane (TPU) is widely applied as a coating for medical devices due to its stability and ideal mechanical properties, especially for implantable metals like stents, grafts, or heart valves. These devices often need to be crimped to smaller diameters, requiring flexibility. Controlling temperature and humidity helps prevent fiber bonding, which can otherwise interfere with TPU’s crimping ability. Figure 5c shows TPU fibers processed in DMAc, displaying their optimized microstructure.
Active ingredients
Many active ingredients commonly used in electrospinning—such as proteins, amino acids, vitamins, peptides, bacteria, live cells, or pharmaceuticals—are sensitive to temperature and humidity. High temperatures can degrade their native structure, while high humidity levels may cause hydrolysis, reducing effectiveness. In electrospraying, additives like surfactants and salts are used to improve particle suspension and surface tension but can be affected if temperature and humidity are not well controlled. The Fluidnatek Environmental Control Unit allows precise control from 18°C to 45°C (±1°C) and 10% to 80% (±3%) relative humidity to prevent these adverse effects, ensuring ideal conditions for thermolabile active ingredients or additives.
Fiber Properties and Morphology in Electrospun Materials
When developing an electrospinning or electrospraying process, optimizing from the start (R&D phase) is crucial for producing consistent and reproducible fibers or particles with defined properties. Uniform fiber morphology is essential to maintain key mechanical properties such as tensile strength, modulus, elongation, suture retention strength, and burst pressure. Additionally, fiber size can be modified to control the porosity of electrospun materials. The appearance of defects like beads and splashes in fiber morphology can also be strongly influenced by environmental conditions.
For example, producing gelatin fibers at 25°C and 70% RH leads to a beaded fiber structure (Figure 6a). At high humidity, water in the solution evaporates slowly, reducing solution viscosity and preventing full polymer elongation during jet formation, resulting in beads. These beaded structures can impact the mechanical properties, pore size, porosity, and potential release profile of active ingredients (e.g., in pharmaceuticals or cosmetics made via electrospinning or electrospraying).
Figure 6a
Figure 6b
Image 6. Gelatin fibers produced under varying humidity conditions: a) 25°C, 70% RH, and b) 25°C, 35% RH. Fibers created at high relative humidity display beaded structures, while those generated at lower humidity levels are smooth, round, and elongated. Images by Nanoscience Instruments.
Adjusting the electrospinning process to use a relative humidity of 35% for gelatin fibers results in rounded, consistent fiber morphology (Figure 6b). Lower humidity optimizes solvent evaporation, allowing material in the jet phase to elongate effectively and solidify at an ideal rate.
Temperature is another crucial factor influencing fiber characteristics and morphology, interacting closely with relative humidity and solvent properties. Humidity and temperature are interconnected variables; for instance, a rise in temperature may lower the relative humidity within the electrospinning chamber, impacting fiber thickness. Increasing temperature typically reduces solution viscosity, enabling faster movement of polymer chains, resulting in thinner fibers. However, higher evaporation rates due to increased temperature can also lead to thicker fibers. Therefore, achieving the optimal temperature balance is essential for specific application needs.
Generally, hydrophilic polymer fibers electrospun at low temperatures and high humidity will have smaller diameters, while those produced at higher temperatures and lower humidity will yield larger fiber diameters. For hydrophobic polymers, high humidity during electrospinning may cause water droplets to collect on the fiber surface, resulting in porous structures. These pores, while often considered defects that reduce mechanical strength, can be desirable for certain applications.
Scalability
Environmental control is essential when scaling the electrospinning process from initial proof-of-concept and feasibility studies to pilot production and, ultimately, industrial-scale manufacturing. The process’s stability, consistency, and reproducibility depend significantly on maintaining specific environmental conditions, along with other key factors.
As an example of the importance of environmental conditions in scaling electrospinning, polyacrylonitrile (PAN) fibers in dimethylformamide (DMF) were produced using 60 needles under controlled conditions. Optimal results were achieved with a flow rate of 30 mL/h (0.5 mL/h per needle) at 25°C, 35% relative humidity, and 90 m³/h air flow. However, when the number of needles doubled from 60 to 120, the flow rate increased to 60 mL/h to maintain a consistent rate per needle. Using the same environmental settings in this scaled-up configuration resulted in defects, specifically stacking and cross-stacking (Figure 7a). Stacking refers to fiber buildup from the collector to the needle, while cross-stacking describes fibers accumulated between fibers from separate needles.
Figure 7a
Figure 7b
Photo 7. Impact of temperature and humidity control on scaling PAN production: a) shows stacking and cross-stacking defects; b) optimized temperature, humidity, and airflow settings with defect-free production. Images by Nanoscience Instruments.
To address these issues, environmental parameters were refined, yielding a stable process at 40°C, 18% RH, and 120 m³/h airflow (Figure 7b). These optimized conditions, summarized in Table 1, increased evaporation rates and enabled faster solvent removal from the chamber due to higher airflow. This adjustment led to smooth, uniform PAN fiber production.
By controlling environmental conditions, the process benefits from improved solvent removal, prevention of needle clogging, and minimized defects, whether during sample development or large-scale material roll production. These optimized settings not only stabilize the process but also enhance electrospinning throughput (Table 1), making industrial-scale production feasible. The Environmental Control Unit thus enables seamless scaling from R&D to process development, pilot production, and finally to industrial manufacturing. The ECU’s core requirements include: 1) Versatility: full control over heating, cooling, drying, and humidifying; 2) Stability: precise and consistent temperature and humidity around set points for reliable processing; 3) Agility: the speed at which the ECU reaches desired environmental settings. The Fluidnatek Environmental Control Unit delivers all these features.
Needles
Flow Rate
Environmental conditions
Result
60
30 mL/h
25°C, 35% RH, air flow of 90 m3/h
Stable process
120
60 mL/h
25°C, 35% RH, air flow of 90 m3/h
Stacking & cross-stacking defects
120
60 mL/h
40°C, 18% RH, air flow of 120 m3/h
Stable process
120
120 mL/h
40°C, 18% RH, air flow of 120 m3/h
Stable & increased throughput
Environmental Control IN ELECTROSPINNING with Fluidnatek ECU
Safety
Safety is a crucial consideration in electrospinning, as it often involves the use of flammable or toxic solvents, as well as potentially hazardous polymers and additives. The Environmental Control Unit (ECU) developed by Fluidnatek incorporates several safety features to ensure stable and safe conditions during the electrospinning process.
Actively Regulated Exhaust System The system includes differential pressure sensors integrated into a control loop with an extraction fan, ensuring optimal ventilation while maintaining slightly negative pressure within the chamber. In case of a ventilation failure, the system shuts down safely to avoid the accumulation of harmful solvent vapors. This exhaust system works in tandem with the ECU to maintain stable environmental conditions, including temperature (18°C to 45°C ± 1°C), relative humidity (10% to 80% ± 3%), and airflow (50 m³/h to 180 m³/h).
Inert Atmosphere For applications involving large quantities of highly flammable or explosive solvents, the ECU can be equipped with a nitrogen loop. Combined with an oxygen sensor, this feature ensures that the oxygen concentration remains below the Lower Explosion Limit (LEL), maintaining safe conditions. The user can set a desired oxygen concentration limit, and the system will automatically adjust to keep the levels within safe parameters.
CONCLUSIONS
The Environmental Control Unit (ECU) plays a vital role in the electrospinning process. The environmental conditions within the electrospinner’s chamber can significantly affect the properties of the electrospun materials, even when other process variables remain constant. Fluidnatek understands the critical importance of this, which is why we designed our ECU specifically for electrospinning processes. Our newly released ECU 2nd Generation offers enhanced features compared to its predecessor. Key qualities of an excellent ECU include versatility, stability, and agility.
Fluidnatek ECU 2nd Generation
As discussed, environmental control is essential because materials, solvents, and additives each have unique chemical and physical properties, and their behavior during electrospinning is highly influenced by the environment. Consequently, the properties of electrospun or electrosprayed materials can vary based on the chamber’s environmental conditions. It is crucial to determine the optimal temperature and relative humidity settings for each specific material and process. Furthermore, proper environmental control is vital for scaling up production and ensuring safety. Fluidnatek is proud to offer a superior Environmental Control Unit that works seamlessly with our electrospinning equipment. As manufacturers of electrospun and electrosprayed materials at an industrial scale, we are acutely aware of the importance of precise environmental control for successful electrospinning.
ESP