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

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 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 overtime 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 show any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was slow and remained above the minimal inhibitory concentration for gentamicin sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic payload 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.

Biomaterials and Extracellular Vesicle Delivery: Current Status, Applications and Challenges

“…Collagen has proven to be useful in medical applications as a delivery tool. Similar to the natural biopolymers discussed thus far, collagen has been utilized to deliver drugs [ 92 , 93 ], cells [ 94 , 95 ], and bioactive substances with antioxidant properties [ 96 ]. It is also possible to deliver growth factors using collagen [ 97 , 98 ].…”