Ex vivo comparison of V.A.C.® Granufoam Silver™ and V.A.C.® Granufoam™ loaded with a first-in-class bis-dialkylnorspermidine-terphenyl antibiofilm agent

Kaden B Rawson; Travis Neuberger; Tyler B Smith; Isaac J Bell; Ryan E Looper; Paul R Sebahar; Travis J Haussener; Hariprasada Reddy Kanna Reddy; Brad M Isaacson; John Shero; Paul F Pasquina; Dustin L Williams

doi:10.1016/j.bioflm.2023.100142

Ex vivo comparison of V.A.C.® Granufoam Silver™ and V.A.C.® Granufoam™ loaded with a first-in-class bis-dialkylnorspermidine-terphenyl antibiofilm agent

Biofilm. 2023 Jul 11:6:100142. doi: 10.1016/j.bioflm.2023.100142. eCollection 2023 Dec 15.

Authors

Kaden B Rawson^{1

2

3}, Travis Neuberger^{1

2

4

3}, Tyler B Smith^{1

2}, Isaac J Bell^{1

2}, Ryan E Looper^{5

6}, Paul R Sebahar^{5

6}, Travis J Haussener^{5

6}, Hariprasada Reddy Kanna Reddy^{5

6}, Brad M Isaacson^{2

7

8}, John Shero⁹, Paul F Pasquina^{7

10}, Dustin L Williams^{1

2

4

6

7

11}

Affiliations

¹ Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA.
² Bone and Biofilm Research Lab, University of Utah, Salt Lake City, UT, USA.
³ Carle Illinois College of Medicine, University of Illinois, Urbana, IL, USA.
⁴ Department of Biomedical Engineering, University of Utah, UT, USA.
⁵ Department of Chemistry, University of Utah, Salt Lake City, UT, USA.
⁶ Curza Global, LLC, Salt Lake City, UT, USA.
⁷ The Center for Rehabilitation Sciences Research, Department of Physical Medicine and Rehabilitation, Uniformed Services University, Bethesda, MD, USA.
⁸ The Geneva Foundation, Tacoma, WA, USA.
⁹ Extremity Trauma and Amputation Center of Excellence, Joint Base San Antonio Fort Sam Houston, San Antonio, TX, USA.
¹⁰ Department of Rehabilitation, Walter Reed National Military Medical Center, Bethesda, MD, USA.
¹¹ Department of Pathology, University of Utah, Salt Lake City, UT, USA.

Abstract

Implementation of negative pressure wound therapy (NPWT) as a standard of care has proven efficacious in reducing both the healing time and likelihood of nosocomial infection among pressure ulcers and traumatic, combat-related injuries. However, current formulations may not target or dramatically reduce bacterial biofilm burden following therapy. The purpose of this study was to determine the antibiofilm efficacy of an open-cell polyurethane (PU) foam (V.A.C.® Granufoam™) loaded with a first-in-class compound (CZ-01179) as the active release agent integrated via lyophilized hydrogel scaffolding. An ex vivo porcine excision wound model was designed to perform antibiofilm efficacy testing in the presence of NPWT. PU foam samples loaded with a 10.0% w/w formulation of CZ-01179 and 0.5% hyaluronic acid were prepared and tested against current standards of care: V.A.C.® Granufoam Silver™ and V.A.C.® Granufoam™. We observed statistically significant reduction of methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii biofilms with the CZ-01179 antibiofilm foam in comparison to current standard of care foams. These findings motivate further development of an antibiofilm PU foam loaded with CZ-01179.

Keywords: A. baumannii; Biofilm; MRSA; Negative pressure wound therapy.