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Pre-clinical Evaluation of a Third Generation Absorbable Antibacterial Envelope

Published:January 21, 2023DOI:https://doi.org/10.1016/j.hrthm.2023.01.018

      ABSTRACT

      Background

      The TYRX absorbable antibacterial envelope has been shown to stabilize implantable cardiac devices and reduce infection. A third-generation envelope was developed to reduce surface roughness with a redesigned multifilament mesh and enhanced form-factor but identical polymer coating and antibiotic concentrations as the currently available second-generation envelope.

      Objective

      To compare drug elution, bacterial challenge efficacy, stabilization, and absorption of second- vs. third-generation envelopes.

      Methods

      Antibiotic elution was assessed in vitro and in vivo. For efficacy against gram+/gram- bacteria, 40 rabbits underwent device insertions with or without third-generation envelopes. For stabilization (migration, rotation), 5 sheep were implanted with 6 devices each in second- or third-generation envelopes. Pre-specified acceptance criteria were <83 mm migration and <90 degrees rotation. Absorption was assessed via gross pathology.

      Results

      Elution curves were equivalent (similarity factors ≥50 per FDA guidance). Third-generation envelopes eluted antibiotics above minimal inhibitory concentration (MIC) in vivo at 2hr post-implant through 7d, consistent with second-generation envelopes. Bacterial challenge showed reductions (p<0.05) in infection with second- and third-generation envelopes. Device migration was 5.5±3.5 (third-generation) vs. 9.9±7.9 mm (second-generation) (p<0.05). Device rotation was 18.9±11.4 (third-generation) vs. 17.6±15.1 degrees (second-generation) and did not differ (p=0.79). Gross pathology confirmed absence of luminal mesh remainders and no differences in peri-device fibrosis at 9 or 12wks.

      Conclusion

      The third-generation TYRX absorbable antibacterial envelope demonstrated equivalent pre-clinical performance to the second-generation envelope: antibiotic elution curves were similar, elution was above MIC for 7d, infections were reduced compared to no envelope, and acceptance criteria for migration, rotation, and absorption were met.

      Graphical abstract

      Keywords

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