Category Archives: Biomedical

DRUG-LOADED ELECTROSPUN YARNS OF APPLICATION AS ANTIMICROBIAL SURGICAL SUTURES

Electrospun surgical sutures

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

Ophthalmologic applications of electrospinning

Introduction

In recent years, electrospinning has aroused much interest in the biomedical field of ophthalmology due to the possibilities it offers for the treatment of various pathologies affecting the eye. Especially with the proliferation of available electrospinning biomaterials.

Electrospinning is a fiber production technique based on the use of powerful electric fields, which are applied to a solution formed by one or more polymers (and alternatively other types of materials as well, including even biological materials) and one or more solvents. This solution, usually contained in a syringe-type container when working at laboratory scale, is pumped through a needle or capillary. In electrospinning, a high voltage is applied to the tip of the needle, so that the accumulation of electrical charges on the surface of the droplet produces an electrical repulsion effect between the particles of the solution, until finally the electrical force overcomes the surface tension of the droplet, stretching it to generate a jet. As the jet moves toward the collector, which is at zero or negative voltage, the solvent evaporates, generating polymer fibers that are eventually deposited onto the collector.

The fibers generated by electrospinning can vary from the nanometer and micrometer range according to the interest of each particular application, which is very interesting for biomedical applications, since the proper selection of the polymer allows the creation of fibrillar structures that resemble the extracellular matrix (ECM) in size and arrangement. It is possible to use different electrospinning biomaterials: biopolymers, bioabsorbable polymers, non-bioabsorbable polymers, etc, as long as they are of biomedical grade.

Electrospinning applications in ophthalmology

Vision is one of the five primary senses of the human being, so any pathology affecting the ocular system has a great impact on people’s quality of life. According to a report by the World Health Organization, at least 2.2 billion people in the world suffer from vision-related pathologies [1]. Of these, it is estimated that almost 1 billion could be preventable or treatable [2].

In this context, fibers generated from electrospinning biomaterials offer a number of advantages in the development of new ocular therapies. Nanofibers offer a very high surface area, which is advantageous for tissue regeneration and controlled drug release applications. In addition, the adjustable porosity of nanofiber matrices favours cell growth and proliferation and does not interfere with tissue respiration and gas exchange.

Main applications of electrospinning in ophthalmology

  1. Controlled drug delivery

Electrospinning is being used to create nanofiber arrays in which drugs and active ingredients are incorporated. The spatial configuration of the nanofibers allows a sustained and controlled release of drugs into the eye in a very efficient manner. The nanofiber matrix is based on appropriately selected electrospinning biomaterials as required by the specific application.

For example, in the treatment of glaucoma, the controlled release of drugs can reduce intraocular pressure for a longer period of time. On the other hand, if the nanofiber matrix is loaded with anti-inflammatory agents, pathologies such as uveitis or post-operative inflammation can be treated more effectively. If antibiotics are used, corneal infections can be treated.

  1. Ocular tissue engineering

Nanofiber arrays generated with electrospinning biomaterials are the ideal support for ocular tissue engineering due to their similarity to the extracellular matrix, thus promoting cell adhesion and proliferation, as well as regeneration of damaged tissues in the eye. These nanofiber matrices can replace damaged corneal tissue, as well as contribute to the regeneration of retinal and optic nerves.

  1. Ocular medical devices

Ocular medical devices, such as intraocular lenses, artificial corneal implants, or even contact lenses, can benefit from the possibility of depositing a thin layer of nanofibers on or around them. In this way, this nanofiber layer will act as an interface between the medical device and the eye, stimulating the growth of cells around the device, thus increasing its biocompatibility and reducing the possibility of rejection. In intraocular devices, this nanofiber interface and subsequent cell proliferation also helps to better fix the implant inside the eye.

Conclusions

Electrospinning is a very versatile technique that has numerous applications in the field of ophthalmology due to its ability to control the characteristics of the nanofibers obtained. These applications are constantly evolving and improving thanks to the new electrospinning biomaterials that are becoming increasingly available. Advances in electrospinning and its applications in ophthalmology will provide researchers and physicians with a powerful tool to improve the quality of life of people with ocular pathologies.

 

References

[1] D. Sakpal et al., “Recent advancements in polymeric nanofibers for ophthalmic drug delivery

and ophthalmic tissue engineering,” in Biomaterials Advances 141 (2022) 213124.

[2] D. Mishra et al., “Ocular application of electrospun materials for drug delivery and cellular

therapies,” in Drug Discovery Today vol. 28, num. 9, 2023.

Electrospun scaffolds for kidney tissue engineering: on the way towards kidney organoids

Chronic kidney disease is one of the deadliest diseases all around the world. Current healing methods mostly rely on transplantation and dialysis. Engineering of kidney tissues in vitro from induced pluripotent stem cells could provide a solution by restoring the function of damaged kidneys. Electrospinning is a technique that has shown promise in the development of physiological microenvironments of several tissues and could be applied in the engineering of kidney tissues as well.

So far several approaches with electrospinning were attempted. Synthetic polymers such as PCL, PLA and PVOH have been explored in the manufacturing of fibers that promote the proliferation and cell-to-cell interactions of kidney cells. Also natural polymers like silk fibroin have been explored alone and in combination with synthetic polymers promoting the differentiation of podocytes and tubular specific cells. Natural polymers are highly interesting but in many cases they do not provide the mechanical resistance required, that is the reason for combining with synthetic polymers which can balance the lack of resistance.

Furthermore, the use of the electrospinning technique in combination with other manufacturing methods such as bioprinting are highly promising aiming to develop more organized, mature and reproducible kidney organoids. It is important to take into account that kidney cells’ behaviour is strongly dictated by the complex 3D microenvironment.

Kidney organoids derived from human induced pluripotent stem cells can be attractive 3D models for different purposes, including to model kidney embryonic development, kidney disease, and renal regeneration. The electrospinning technique is also compatible with live cells encapsulating them in the desired environment.

Electrospinning biomaterials, with their versatile characteristics, are being increasingly utilized in the field of tissue engineering. These biomaterials offer immense potential in the creation of scaffolds that support cell growth and differentiation, which is crucial for tissue regeneration. Electrospinning biomaterials are also being explored for their potential in controlled drug release, enhancing the effectiveness of therapies in various biomedical applications.

Electrospinning have been demonstrated to be a promising technique to develop kidney tissues in vitro. However it is still a challenge the lack of knowledge in the specific stimulus required to create kidney organoids. In essence, electrospinning for tissue engineering offers significant benefits due to its unique ability to create biomimetic structures. It can fabricate fibrous scaffolds that closely resemble the extracellular matrix of tissues, promoting cell growth and tissue regeneration. Furthermore, electrospinning for tissue engineering applications allows control over fiber diameter and porosity, aiding in the customization of scaffolds. Electrospinning for tissue engineering has shown to be promising in areas like bone, skin, organs and vascular grafts. Its versatility enhances the potential of electrospinning for tissue engineering applications, marking a significant step forward in regenerative medicine.

Further information can be found in the paper written by Claudia C. Miranda, Mariana Ramalho, Mariana Moço, Joaquim Cabral, Federico Castelo Ferreira and Paola Sanjuan-Alberte from Universidade de Lisboa.

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