DRUG-LOADED ELECTROSPUN YARNS OF APPLICATION AS ANTIMICROBIAL 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 by means of an electrospun fiber-yarn collector, to which ciprofloxacin has been added as an antimicrobial agent to prevent surgical site infections. In other words, electrospinning technology is positioned as an alternative with high potential for the development of surgical sutures constructed from nanofibers (electrospun nanofibers in this case). The polymer chosen for the yarn has been PHBV, of which 3 variants with different contents of 3HV units have been tested. A complete characterization of the different suture yarns (i.e. the different electrospun yarns obtained) has been carried out, both from the mechanical point of view and their antimicrobial efficacy, showing promising mechanical properties and a high antimicrobial effect.

Introduction

Sutures are a routine surgical procedure to close wounds and join tissues. These types of interventions, due to their intrinsic characteristics, are susceptible to the emergence of pathogens in what are called 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 large number of suture threads have been developed depending on the characteristics of the tissue to be sutured. However, despite the major drawbacks of SSIs, little progress has been made in improving the therapeutic effect of suture threads to prevent SSIs. Generally, the incorporation of antimicrobial substances has been carried out using techniques such as melt spinning, dip coating or soaking, among others. Although these techniques have been shown to be effective to some extent, none of them are able to properly encapsulate the substance of interest, so its release profile and stability over time is not adequately controlled. This is where the electrospinning technique can provide additional value in the development of drug-loaded electrospun yarns.

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.

Materials and methods

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.

Throughput production pilot plant, which 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 by the action of the electric field to form a jet. This increase in the contact surface between the solution and the medium causes the evaporation of the solvent and the creation of nanofibers. This is basically what the electrospinning technique consists of. To generate the suture yarns, an accessory called 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 they approach the funnel, the nanofibers intertwine following the direction of rotation of the funnel, until they finally form a yarn that is continuously collected by a rotating reel. To ensure consistency and reproducibility in the manufacture of all the suture yarns developed, an ECU (Environmental Control Unit) has been used to set specific temperature and relative humidity values, in this case, 30°C and 30% RH, respectively. The Environmental Control Unit has also been developed by Fluidnatek, specifically designed for its electrospinning equipment and for such a particular evaporative process as electrospinning (and electrospraying).

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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