Plastic Surgery Research Council

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Minimizing Implant Infection and Capsular Contracture Through the Use of Antibiotic-Eluting Nanofiber Coatings
Bartlomiej Kachniarz, MD MBA1, Sashank Reddy, MD PhD1, Russell A. Martin, PhD2, Deepa Bhat, MD3, Roger Ortines, BS4, Lloyd S. Miller, MD PhD4, Hai-Quan Mao, PhD2, Justin M. Sacks, MD1.
1Johns Hopkins Hospital, Baltimore, MD, USA, 2Translational Tissue Engineering Center, Baltimore, MD, USA, 3Albany Medical Center, Albany, NY, USA, 4Johns Hopkins University, Baltimore, MD, USA.

PurposeBacterial contamination following implant-based soft tissue reconstruction contributes to significant healthcare costs and patient morbidity. In addition to acute infection, subclinical bacterial colonization is thought to contribute to long-term capsular contracture. The purpose of this study was to design an antibiotic-eluting nanofiber-hydrogel composite sheet for use in implant soft tissue pocket reinforcement. A murine implant infection model was developed to test the impact of the device on implant infection and infection-associated capsule formation.
Methods Polycaprolactone (PCL) impregnated with linezolid and rifampicin was electrospun into a random-pattern sheet and suspended within a nanofiber-hydrogel composite. Interfacial bonding between the nanofibers and hydrogel matrix was used to improve structural integrity of the material. Mechanical properties and antibiotic release kinetics were assessed in vitro. Silicone disk implants were incubated with a bioluminescent Staphylococcus aureus strain for 24 hours. Biofilm formation was confirmed via crystal violet staining. Thirty-five mice were implanted with either the infected implant alone, infected implant with overlying composite sheet, or infected implant with overlying antibiotic-eluting composite sheet. Bioluminescence imaging was used to assess the in vivo bacterial burden between postoperative days 0 and 15. Postmortem bacterial colony forming unit (CFU) quantification, histology, and immunohistochemistry were performed on harvested tissues.
Results A 1mm-thick nanofiber-hydrogel composite sheet embedded with linezolid and rifampicin was designed and demonstrated favorable mechanical properties, suturability, and antibiotic release kinetics (Figure 1).
Use of the antibiotic-eluting composite sheet device resulted in complete prevention of clinical signs of cellulitis and implant exposure. In vivo bacterial luminescence was reduced in the presence of the antibiotic-eluting composite sheet overlay, returning to background signal levels within the study period (Figure 2).
The post-mortem bacterial burden within the peri-implant soft tissue was reduced 600-fold (1.8e2 +/- 1.8e2 versus 1.1e5 +/- 1.5e5, p=0.03), as was average capsule thickness (79 +/- 35 μm versus 274 +/- 194 μm, p=0.001) and relative collagen density within the peri-implant space (31.2 +/- 14.2 % versus 44.5 +/- 15.6 %, p=0.02).
Conclusion An antibiotic-eluting nanofiber-hydrogel composite device was designed to reduce the risk of infection and capsule formation following implant-based soft tissue reconstruction. The device inhibited in vivo bacterial growth following implantation of a contaminated implant in a mouse model. Placement of the antibiotic-eluting sheet overlay led to a reduction in soft tissue cellulitis, implant exposure, and peri-implant capsule formation. The technique permits tailoring of mechanical properties and antibiotic release kinetics of the device to suit a variety of surgical applications. The device provides a platform for local delivery of medication into the peri-implant space combined with soft tissue reinforcement.


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