Heparin-mediated antibiotic delivery from an electrochemically-aligned collagen sheet

Article type: Research Article

Authors: Cheng, Olivia T.^a | Stein, Andrew P.^{b; †} | Babajanian, Eric^{a; †} | Hoppe, Kathryn R.^b | Li, Shawn^b | Jung, Hyungjin^c | Abrol, Anish^b | Akkus, Anna^d | Younesi, Mousa^c | Altawallbeh, Ghaith^e | Ghannoum, Mahmoud A.^f | Bonfield, Tracey^e | Akkus, Ozan^c | Zender, Chad A.^g;

Affiliations: [a] Case Western Reserve University (CWRU) School of Medicine, Cleveland, OH, USA | [b] Department of Otolaryngology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA | [c] Department of Biomedical Engineering, CWRU, Cleveland, OH, USA | [d] Department of Macromolecular Science & Engineering, CWRU, Cleveland, OH, USA | [e] Department of Immunology, CWRU, Cleveland, OH, USA | [f] Center for Medical Mycology, CWRU and University Hospitals Cleveland Medical Center, Cleveland, OH, USA | [g] Department of Otolaryngology, University of Cincinnati, Cincinnati, OH, USA

Correspondence: [*] Corresponding author: Chad A. Zender, MD, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. E-mail: [email protected]

Note: [†] Shared second authorship.

Abstract: BACKGROUND:Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue. OBJECTIVE:To develop and evaluate a novel, biologic antimicrobial coating for medical implants. METHODS:Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per a protocol developed by our group. Sheets were incubated in antibiotic solution (gentamicin or moxifloxacin) overnight, and in vitro activity was assessed with five-day diffusion assays against Pseudomonas aeruginosa. Antibiotic release over time from gentamicin-infused sheets was determined using in vitro elution and high performance liquid chromatography (HPLC). RESULTS:Collagen-heparin-antibiotic sheets demonstrated larger growth inhibition zones against P. aeruginosa compared to collagen-antibiotic alone sheets. This activity persisted for five days and was not impacted by rinsing sheets prior to evaluation. Rinsed collagen-antibiotic sheets did not produce any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was gradual and remained above the minimal inhibitory concentration for gentamicin-sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic load within 24 hours. Overall, heparin-associated sheets demonstrated larger inhibition zones against P. aeruginosa and prolonged elution profile via HPLC. CONCLUSION:We developed a novel, local antibiotic delivery system that could be used to coat medical implants/hardware in the future and reduce post-operative infections.

Keywords: Local antibiotic delivery, electrochemically compacted collagen sheet, collagen sheet with heparin, Pseudomonas aeruginosa , implantable medical devices and hardware

DOI: 10.3233/BME-201133

Journal: Bio-Medical Materials and Engineering, vol. 32, no. 3, pp. 159-170, 2021