Induction Heating Triggers Antibiotic Release and Synergistic Bacterial Killing on Polymer-Coated Titanium Surfaces

Jan C Kwan; Ronald S Flannagan; Mónica Vásquez Peña; David E Heinrichs; David W Holdsworth; Elizabeth R Gillies

doi:10.1002/adhm.202202807

Induction Heating Triggers Antibiotic Release and Synergistic Bacterial Killing on Polymer-Coated Titanium Surfaces

Adv Healthc Mater. 2023 Sep;12(22):e2202807. doi: 10.1002/adhm.202202807. Epub 2023 May 1.

Authors

Jan C Kwan^{1

2}, Ronald S Flannagan³, Mónica Vásquez Peña^{1

2}, David E Heinrichs³, David W Holdsworth^{1

2

4

5}, Elizabeth R Gillies^{1

2

6

7}

Affiliations

¹ School of Biomedical Engineering, The University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5B9, Canada.
² Bone and Joint Institute, The University of Western Ontario, The Sandy Kirkley Centre for Musculoskeletal Research, University Hospital B6-200, London, Ontario, N6G 2V4, Canada.
³ Department of Microbiology and Immunology, The University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5C1, Canada.
⁴ Imaging Research Laboratories, Robarts Research Institute, The University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 2B8, Canada.
⁵ Department of Medical Biophysics, The University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5C1, Canada.
⁶ Department of Chemistry, The University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5B7, Canada.
⁷ Department of Chemical and Biochemical Engineering, The University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5B9, Canada.

PMID: 37053473
DOI: 10.1002/adhm.202202807

Abstract

Infection is a major complication associated with orthopedic implants. It often involves the development of biofilms on metal substrates, which act as barriers to the host's immune system and systemic antibiotic treatment. The current standard of treatment is revision surgery, often involving the delivery of antibiotics through incorporation into bone cements. However, these materials exhibit sub-optimal antibiotic release kinetics and revision surgeries have drawbacks of high cost and recovery time. Herein, a new approach is presented using induction heating of a metal substrate, combined with an antibiotic-loaded poly(ester amide) coating undergoing a glass transition just above physiological temperature to enable thermally triggered antibiotic release. At normal physiological temperature, the coating provides a rifampicin depot for >100 days, while heating of the coating accelerates drug release, with >20% release over a 1-h induction heating cycle. Induction heating or antibiotic-loaded coating alone each reduce Staphylococcus aureus (S. aureus) viability and biofilm formation on Ti, but the combination causes synergistic killing of S. aureus as measured by crystal violet staining, determination of bacterial viability (>99.9% reduction), and fluorescence microscopy of bacteria on surfaces. Overall, these materials provide a promising platform enabling externally triggered antibiotic release to prevent and/or treat bacterial colonization of implants.

Keywords: antibacterials; biofilms; coatings; induction heating; orthopedic infections; poly(ester amide).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents* / chemistry
Biofilms
Coated Materials, Biocompatible / chemistry
Coated Materials, Biocompatible / pharmacology
Heating
Humans
Polymers
Staphylococcal Infections* / drug therapy
Staphylococcus aureus
Titanium / chemistry
Titanium / pharmacology

Substances

Anti-Bacterial Agents
Titanium
Polymers
Coated Materials, Biocompatible