Antibacterial effect of electrospun polycaprolactone/polyethylene oxide/vancomycin nanofiber mat for prevention of periprosthetic infection and biofilm formation

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Abstract

Objective

In this study, we developed a biocompatible and biodegradable vancomycin (VM)-eluting electrospun poly(ɛ-caprolactone) (PCL)/polyethylene oxide (PEO)/VM/PCL nanofiber mat. The purpose of this study was to evaluate the efficacy of this nanofiber mat for preventing methicillin-resistant Staphylococcus aureus (MRSA) biofilm on the ossicular prostheses and otitis media.

Materials and methods

Fabrication of VM eluting nanofiber mat was carried out using PCL and PEO. The release of VM was assessed by spectrophotometry in vitro. The antibacterial effect was evaluated by inhibition zone test and biofilm formation test in vitro. And prevention of MRSA infection by guinea pig was assessed by otoendoscopy, temporal bone CT and histopathologic examination in vivo.

Results

VM released followed a triphasic pattern. VM eluting nanofiber mat prevented MRSA biofilm formation on the surface of ossicular prostheses regardless of materials in vitro, and MRSA otitis media in vivo. Otoendoscopy, temporal bone CT, and histopathologic findings revealed well ventilated middle ear.

Conclusion

From these results, VM eluting nanofiber mat may be a promising method for prevention of MRSA periprosthetic infection and biofilm formation.

Introduction

Periprosthetic infections are thought to be caused by invading bacteria at the time of surgery. Treating infected prosthesis is exceedingly difficult, especially due to the inherent difficulties of treating an established biofilm [1]. The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection after middle ear surgery has recently increased [2]. Once a MRSA biofilm has formed on an implanted medical device such as ossiculoplasty prostheses, implantable hearing devices, and silicone prostheses, it is difficult to disrupt. Biofilm-infected implants must often be removed and replaced, placing the patient at increased risk of complications such as persistent nontractable infection or endocochlear inflammation in cochlear implant users [3], [4]. Current antimicrobial therapies for biofilm have proven largely unsuccessful by conventional systemic antibiotic treatment [5]. Biofilm and chronic inflammation may have a role in prostheses extrusion [6]. By extended release of antibiotic locally, higher effective concentrations may be achieved while avoiding potentially toxic systemic concentrations [7], [8]. Lee et al. reported effective treatment of MRSA otitis media using local delivery of vancomycin combined with pluronic F-127 gel [9]. To date, there are no reports on preventive antibiotic loaded nanofiber mat against middle ear periprosthetic infection or biofilm by MRSA.

Electrospun porous nanofiber scaffolds have been effective in delivering drug or biologically active molecules such as growth factors [8], [9]. Poly(ɛ-caprolactone) (PCL), a semicrystalline biodegradable polyester, belongs to the poly(a-hydroxy acids) family. Its copolymers, lactides and glycolide are getting increasing attention because of their controllable biodegradation rates in the desirable ranges (slower) and also more suitable and tailor-made mechanical properties (more flexible and softer) for some applications such as long-term drug delivery and tissue repair and regeneration [10], [11], [12], [13].

In this study, we developed a biocompatible and biodegradable vancomycin (VM)-eluting electrospun PCL/(PEO/VM)/PCL nanofiber mat. The purpose of this study was to evaluate the efficacy of this nanofiber mat for preventing MRSA biofilm on the prostheses and otitis media.

Section snippets

Fabrication and characterization of nanofiber mat

Poly(ɛ-caprolactone) (PCL, Mn = 70,000–90,000) and poly(ethylene oxide) (PEO, Mw = 900,000) were purchased from Sigma-Aldrich (St. Louis, MO, USA). PCL was prepared at a fixed concentration of 10% (w/w) in an 80:20 mixture of methylene chloride (MC):dimethylformamide (DMF). As a drug, we used vancomycin (VM, Samjin Pharm, Seoul, Korea).

As shown in Fig. 1A, to fabricate sandwiched nanofibrous mats, PCL and PEO/VM solutions were electrospun in a layer-by-layer manner in a 10-ml syringe with a 21 G

Morphology and functionalization of the electrospun nanofiber mat

The surface and cross-sectional optical images of Fig. 1B and C show a fibrous mat consisting of three-layered electrospun fibers, PCL/(PEO/VM)/PCL fibers, with a total thickness of 0.21 mm. In the cross-sectional optical image, the red dye was mixed with the PEO/VM to demonstrate the PEO/VM region in the multi-layered mat and the red color means the PEO/VM region. As shown in the SEM image of Fig. 1D, electrospun PCL nanofibers were used as a porous structured layer for controlling drug

Discussion

The danger of MRSA infections result from not only the emergence of multidrug resistance but also the occurrence of strong biofilm-forming bacteria [15]. Once a bacterial biofilm has formed on an implanted medical device or damaged tissue, it is difficult to disrupt. Conventional systemic delivery of antibiotics often has little effect, because of poor penetration into ischemic and necrotic tissue and can cause systemic toxicity with associated renal and hepatic complications. A general

Conclusion

Results of in vitro release and anti-MRSA experiments suggest that the developed VM containing NF mat are capable of effectively delivering VM in a controlled fashion with prolonged duration. These results indicate that electrospun VM-eluting PCL/(PEO/VM)/PCL NFs are good candidates for prevention of MRSA infection.

Acknowledgement

This study was supported by Fishery Commercialization Technology Development Program, Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea (grant no. A120942).

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