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Biomedical

Cell-Seeded Scaffolds: Revolutionizing Biomedical Engineering for Tissue Regeneration

Posted on by Vicente Zaragozá
Cell-Seeded Scaffold
17
Feb

For decades, researchers in biomedical engineering have strived to unlock the secrets of tissue engineering and tissue regeneration. The ultimate goal: to repair or replace damaged tissues and organs, offering hope to millions suffering from injuries and diseases. One of the most promising approaches in this field involves the creation of cell-seeded scaffolds, structures that mimic the natural environment of cells and guide their growth and development.

Cell-Seeded Scaffolds

The Promise of Cell-Seeded Scaffolds

Imagine a tiny, three-dimensional framework, meticulously designed to support the growth of new tissue. That’s essentially what a cell-seeded scaffold is. These scaffolds provide structural support for cells to attach, proliferate, and differentiate, ultimately forming functional tissue. The beauty of this approach lies in its potential to create personalized, biocompatible implants that seamlessly integrate with the body.

But how are these scaffolds made, and what makes them so effective? The answer lies in a combination of advanced materials science, cell biology, and innovative fabrication techniques.

Electrospinning: A Key Technology for Scaffold Fabrication

Among the various methods used to create tissue affolds, electrospinning stands out as a versatile and powerful technique. This process uses an electrical field to draw charged threads of polymer solutions, creating nanofibers that form a porous, three-dimensional structure. The resulting scaffolds closely resemble the extracellular matrix (ECM), the natural environment surrounding cells in the body.

Advantages of Electrospinning in Tissue Engineering

The advantages of electrospinning for biomedical tissue engineering are numerous:

  • Tunable architecture: Electrospinning allows for precise control over fiber diameter, porosity, and alignment, enabling the creation of scaffolds tailored to specific tissue types.

  • Versatile materials: A wide range of polymers, both natural and synthetic, can be electrospun, allowing for the selection of materials with specific properties such as biodegradability, biocompatibility, and mechanical strength.

  • Scalability: The electrospinning process can be scaled up for mass production, making it a viable option for clinical applications.

Collagen Electrospinning: A Natural Choice

Collagen, the most abundant protein in the human body, is a popular choice for electrospinning scaffolds. Its inherent biocompatibility, biodegradability, and ability to promote cell adhesion make it an ideal material for tissue engineering applications. Collagen electrospinning cell seeding techniques are thus widely studied.

Applications of Collagen Scaffolds

Collagen scaffolds can be used to regenerate and repair different tissues, including:

  • Skin: Collagen scaffolds can promote wound healing and reduce scarring.
  • Bone: They can guide the formation of new bone tissue for fracture repair and bone regeneration.
  • Cartilage: They can support the growth of chondrocytes (cartilage-forming cells) for treating osteoarthritis and other cartilage defects.
  • Blood vessels: Collagen scaffolds can be used to create vascular grafts for bypass surgery and other cardiovascular applications.

Bio-Electrospinning: Seeding Cells During Scaffold Formation

While traditional methods involve seeding cells onto pre-fabricated scaffolds, a more advanced approach—known as bio-electrospinning cell seeding—integrates cells directly into the electrospinning process. This technique involves suspending cells in the polymer solution and simultaneously electrospinning the polymer while encapsulating the cells within the fibers.

Benefits of Bio-Electrospinning

The benefits of bio-electrospinning are significant:

  • Enhanced cell viability: Encapsulating cells within fibers protects them from harsh conditions during electrospinning, improving their survival rate.
  • Uniform cell distribution: Bio-electrospinning ensures homogenous distribution of cells throughout the scaffold, promoting uniform tissue formation.
  • Improved cell-matrix interactions: Direct encapsulation allows intimate contact between cells and scaffold material, enhancing adhesion, proliferation, and differentiation.
Characterization of the 3DPCL-GelMA Scaffold

Characterization of the 3DPCL-GelMA Scaffold. (a) A scanning electron microscope (SEM) image showing the cross-section of melt electrospun polycaprolactone (PCL) fibers, arranged in a porous network. The scale bar represents 30 µm. (b) An SEM image depicting a 3D-printed PCL-GelMA (PG) scaffold composed of 50 stacked layers, highlighting its organized microstructure. The scale bar represents 200 µm. (e) A 3DPCL-GelMA scaffold with cells co-cultured, illustrating cell attachment and distribution within the scaffold structure. (f) A 3DPCL-GelMA scaffold after the hydrogel component has been removed, revealing the remaining fibrous architecture. Reference: Kong et al., 2024.

Beyond the Basics: Advanced Electrospinning Techniques

Researchers are continuously developing new electrospinning techniques to further enhance scaffold properties. Some advanced approaches include:

Coaxial Electrospinning

This technique uses two concentric needles to create core-shell fibers. It allows encapsulation of cells or growth factors within the core fiber structure for controlled release or targeted delivery.

Melt Electrospinning Writing (MEW)

MEW offers precise control over molten polymer deposition. This enables highly defined 3D scaffolds with controlled architecture and mechanical properties.

Combining Electrospinning with Electrospraying

Combining electrospinning with electrospraying produces 3D scaffolds that incorporate stem cells directly into their structure. This technique enhances cell integration within scaffolds.

Hybrid 3D Printing and Electrospinning

This method combines 3D printing with electrospinning to fabricate complex tissue structures like vascular patches or organ-like constructs.

These advanced techniques offer unprecedented control over scaffold properties and cell behavior, paving the way for more effective therapies in biomedical engineering tissue regeneration.

histological cross-sections of scaffolds seeded with cells

Illustration of histological cross-sections of scaffolds seeded with cells after different cultivation periods: (A) After 1 day, showing initial cell attachment and distribution (magnification: ×200). (B) After 15 days, revealing enhanced cell proliferation and scaffold integration (magnification: ×100). Scale bars: 50 µm. [Braghirolli et al., 2015].

Challenges and Future Directions

While cell-seeded scaffolds hold immense promise for tissue engineering, several challenges remain:

  • Scalability: Scaling up production while maintaining quality is critical for clinical translation.
  • Vascularization: Engineering functional blood vessels within scaffolds is essential for nutrient delivery.
  • Immune response: Minimizing immune reactions is vital for long-term success.

Future Research Goals

Future research efforts will focus on:

  • Developing biomaterials with improved biocompatibility.
  • Incorporating bioactive molecules like growth factors into scaffolds.
  • Designing more sophisticated scaffold architectures that mimic native tissues.
  • Promoting vascularization strategies while minimizing immune responses.

Conclusion

Cell-seeded scaffolds represent a groundbreaking advancement in biomedical engineering. By combining innovative technologies like collagen electrospinning cell seeding with advanced fabrication techniques such as bio-electrospinning or coaxial electrospinning, researchers are pushing the boundaries of what’s possible in regenerative medicine. With continued innovation, these technologies could revolutionize treatments for injuries and diseases—bringing us closer to a future where personalized tissue implants are readily available.

References:

Author: Wee-Eong TEO

  1. Ang H Y, Irvine S A, Avrahami R, Sarig U, Bronshtein T, Zussman E, Boey F Y C, Machluf M, Venkatraman. Characterization of a bioactive fiber scaffold with entrapped HUVECs in coaxial electrospun core-shell fiber. Biomatter 2014; 4: e28238. View
  2. Braghirolli D I, Zamboni F, Acasigua G A X, Pranke P. Association of electrospinning with electrospraying: a strategy to produce 3D scaffolds with incorporated stem cells for use in tissue engineering. International Journal of Nanomedicine 2015; 10: 5159. 
  3. Erben J, Jirkovec R, Kalous T, Klicova M, Chvojka J. The Combination of Hydrogels with 3D Fibrous Scaffolds Based on Electrospinning and Meltblown Technology. Bioengineering. 2022; 9(11):660. 
  4. Kong X, Zhu D, Hu Y, Liu C, Zhang Y, Wu Y, Tan J, Luo Y, Chen J, Xu T, Zhu L. Melt electrowriting (MEW)-PCL composite Three-Dimensional exosome hydrogel scaffold for wound healing. Materials & Design 2024; 238: 112717. 
  5. Lee H, Kim G H. Enhanced cellular activities of polycaprolactone/alginate-based cell-laden hierarchical scaffolds for hard tissue engineering applications. Journal of Colloid and Interface Science 2014; 430: 315.
Biomedical

Visionary solutions: electrospun implants giving new hope to nerve recovery

Posted on by Vicente Zaragozá
Implantes Electrospun en la Recuperación de Nervios Periféricos
19
Dec

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:

  1. Customizability: Physical properties like mechanical strength and drug release rates can be tuned.
  2. Biocompatibility: Synthetic polymers such as polycaprolactone (PCL) and polylactic acid (PLA) are widely used due to their compatibility with biological systems.
  3. 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.
electrospun material implantation procedure in a rat sciatic nerve crush model.

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:

  1. Polylactic Acid (PLA): Known for its slow degradation rate, PLA provides a robust structure but can be brittle.
  2. Polycaprolactone (PCL): Offers excellent flexibility and strength, ideal for implants requiring pliability.
  3. 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

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.

Biomedical

DRUG-LOADED ELECTROSPUN YARNS OF APPLICATION AS ANTIMICROBIAL SURGICAL SUTURES

Posted on by Vicente Zaragozá
Electrospun surgical sutures
03
Jun

Electrospinning for Drug-Loaded Surgical Sutures

The objective of the research work presented in this application note is to develop a suture thread composed of fibers obtained by electrospinning (surgical suture yarns made of electrospun fibers) and interwoven using an electrospun fiber-yarn collector. Ciprofloxacin has been added as an antimicrobial agent to prevent surgical site infections.

In other words, electrospinning technology is positioned as a high-potential alternative for the development of surgical sutures constructed from nanofibers (electrospun nanofibers in this case).

The polymer chosen for the yarn is PHBV, with three variants containing different 3HV unit contents tested.

A complete characterization of the different suture yarns (i.e., the different electrospun yarns obtained) has been carried out, evaluating both their mechanical properties and antimicrobial efficacy. The results show promising mechanical properties and a high antimicrobial effect.

Antimicrobial Properties of Ciprofloxacin-Loaded Electrospun Yarns

Sutures are a routine surgical procedure used to close wounds and join tissues. Due to their intrinsic characteristics, these interventions are susceptible to the emergence of pathogens, leading to what are known as surgical site infections (SSIs).

SSIs cause a large number of medical complications, as well as increased morbidity, mortality, and associated healthcare costs. Over time, a variety of suture threads have been developed based on the characteristics of the tissue to be sutured.

However, despite the significant drawbacks of SSIs, little progress has been made in improving the therapeutic effect of suture threads to prevent these infections.

Generally, the incorporation of antimicrobial substances has been carried out using techniques such as melt spinning, dip coating, or soaking, among others. While these techniques have been shown to be effective to some extent, none of them properly encapsulate the substance of interest. As a result, the release profile and stability over time are not adequately controlled.

This is where the electrospinning technique can provide additional value in the development of drug-loaded electrospun yarns.

Electrospinning for Drug Delivery: A Novel Approach to Encapsulating Bioactive Compounds

In this sense, the technique that has proven to be able to incorporate drugs effectively is electrospinning. Electrospinning allows obtaining nanostructures and microstructures that can incorporate drugs into their polymeric matrix in a single step, thus substantially improving their release process. In addition, another great advantage of using electrospinning for this application is that it is not necessary to use high temperatures to obtain nanofibers, which makes it possible to encapsulate compounds such as proteins, growth factors, peptides, DNA or other substances that would not be possible to encapsulate with other techniques such as melt spinning.

In this scientific contribution, members of Bioinicia‘s R&D department develop a suture thread composed of nanofibers obtained by electrospinning and interwoven by means of a device called electrospun fiber-yarn collection module, an accessory developed by Fluidnatek (Bioinicia Fluidnatek being a subsidiary of the Bioinicia Group), to which ciprofloxacin has been added as an antimicrobial agent.

Mechanical Performance of Electrospun Suture Yarns

There are different biopolymers used in biomedical applications. From PLLA, considered the gold standard, to PEG, PLGA, PDS, PLA or PHA. All of them are polymers that can be processed by electrospinning. Within the PHAs family, which is a biodegradable and highly biocompatible polymer, much research has been done on PHB and, within this, on its copolymer PHBV (poly(3-hydroxybutyrate-co-3-hydroxyvalerate). PHB has high crystallinity and macromolecular organization, resulting in a rigid and brittle material that lacks mechanical strength. On the other hand, PHBV co-polyester shows improved thermal and mechanical properties, which vary depending on the content of 3HV units present in the polyester.

In this work, ciprofloxacin hydrochloride (CPX) has been used as an antimicrobial substance to encapsulate electrospun nanofibers. CPX is an antibiotic belonging to the fluoroquinolone family, with known efficacy against Gram-positive and Gram-negative bacteria.

In this study, 3 types of suture threads based on PHBV polymer with different contents of 3HV units, namely 2%, 10% and 20% molar, have been developed. In all cases, PHBV has been dissolved at 8% wt in TFE (2,2,2-trifluoroethanol). CPX was added at 20% wt in the ratio to the amount of polymer.

Electrospinning for Suture Yarn Production: Process, Equipment, and Material Analysis

The throughput production pilot plant can also implement the electrospun fiber-yarn collector module in its configuration. The solution, contained in a syringe, is pushed by a pump until it emerges from the needle tip.

The high electric field present between the needle tip and the collector elongates the solution, forming a jet due to the electric field’s action. This increases the contact surface between the solution and the medium, causing the evaporation of the solvent and the creation of nanofibers. This is the fundamental process behind the electrospinning technique.

To generate the suture yarns, an accessory called the fiber yarn collector module, developed by Fluidnatek, has been used. This accessory consists of a rotating funnel over which the nanofibers generated by electrospinning are directed.

As the nanofibers approach the funnel, they intertwine following the direction of rotation, eventually forming a yarn that is continuously collected by a rotating reel.

To ensure consistency and reproducibility in the manufacturing of the suture yarns, an Environmental Control Unit (ECU) has been used. The ECU sets specific temperature and relative humidity values—30°C and 30% RH, respectively.

The Environmental Control Unit has also been developed by Fluidnatek, specifically designed for its electrospinning equipment and the unique evaporative process of electrospinning (and electrospraying).

This version makes the information easier to follow while keeping technical details intact.

The mechanical and antimicrobial properties of the different drug-loaded yarns made of electrospun fibers obtained have been evaluated by SEM (scanning electron microscopy) imaging, Fourier transform infrared spectroscopy, wide-angle X-ray scattering, differential scanning calorimetry and in vitro drug release monitoring.

Results and conclusion

The 3 suture yarns generated by electrospinning from PHBV with different concentrations of 3HV units and loaded with CPX show a cylindrical morphology with a total diameter between 300 and 500 μm, composed in turn of individual fibers obtained by the electrospinning process, each of these fibers in turn with an average diameter between 1 and 3 μm. CPX appears in an amorphous state within the yarns and the crystallinity of the polymer decreases as the content of 3HV units increases, which in turn is related to the drug release profile. The presence of CPX in the threads has shown high antibacterial activity for two typical pathogens, one Gram-positive and the other Gram-negative, so these suture threads could be suitable in surgical procedures to prevent SSIs.

Despite the promising mechanical properties and the high antimicrobial effect, the elasticity of the suture yarns generated so far does not reach that of traditional suture yarns, so this parameter should be improved in the future so that this type of yarn could be an alternative to those currently used. But what is clear is that electrospinning is positioned as a serious alternative to produce continuous fiber yarns, and in the specific case that applies to this application note to produce drug-loaded electrospun fiber yarns for medical purposes.

References

Pharmaceutics 2024, 16(2), 220

https://doi.org/10.3390/pharmaceutics16020220

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