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10 25, 2022;16 (10): 16497-16512.

Melimine-Modified 3D-Printed Polycaprolactone Scaffolds for the Prevention of Biofilm-Related Biomaterial Infections.

Silvia Cometta, Robert T Jones, Alfredo Juárez-Saldivar, Bogdan C Donose, Muhammad Yasir, Nathalie Bock, Tim R Dargaville, Karl Bertling, Michael Brünig, Aleksandar D Rakić, Mark Willcox, Dietmar W Hutmacher
Author Information
  1. Silvia Cometta: Faculty of Engineering, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4000, Australia. ORCID
  2. Robert T Jones: Central Analytical Research Facility (CARF), Queensland University of Technology, Brisbane, QLD 4000, Australia. ORCID
  3. Alfredo Juárez-Saldivar: Unidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Reynosa 88740, Mexico.
  4. Bogdan C Donose: School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, QLD 4072, Australia. ORCID
  5. Muhammad Yasir: School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2033, Australia.
  6. Nathalie Bock: Australian Research Council Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D Innovation), Queensland University of Technology, Kelvin Grove, QLD 4059, Australia.
  7. Tim R Dargaville: Centre for Materials Science, School of Chemistry and Physics, Queensland University of Technology, Brisbane, QLD 4000, Australia. ORCID
  8. Karl Bertling: School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, QLD 4072, Australia. ORCID
  9. Michael Brünig: School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, QLD 4072, Australia. ORCID
  10. Aleksandar D Rakić: School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, QLD 4072, Australia. ORCID
  11. Mark Willcox: School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2033, Australia. ORCID
  12. Dietmar W Hutmacher: Faculty of Engineering, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4000, Australia. ORCID
PMID: 36245096 DOI: 10.1021/acsnano.2c05812

Abstract

Biomaterial-associated infections are one of the major causes of implant failure. These infections result from persistent bacteria that have adhered to the biomaterial surface before, during, or after surgery and have formed a biofilm on the implant's surface. It is estimated that 4 to 10% of implant surfaces are contaminated with bacteria; however, the infection rate can be as high as 30% in intensive care units in developed countries and as high as 45% in developing countries. To date, there is no clinical solution to prevent implant infection without relying on the use of high doses of antibiotics supplied systemically and/or removal of the infected device. In this study, melimine, a chimeric cationic peptide that has been tested in Phase I and II human clinical trials, was immobilized onto the surface of 3D-printed medical-grade polycaprolactone (mPCL) scaffolds via covalent binding and adsorption. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) spectra of melimine-treated surfaces confirmed immobilization of the peptide, as well as its homogeneous distribution throughout the scaffold surface. Amino acid analysis showed that melimine covalent and noncovalent immobilization resulted in a peptide density of ∼156 and ∼533 ng/cm, respectively. Furthermore, we demonstrated that the immobilization of melimine on mPCL scaffolds by 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride (EDC) coupling and noncovalent interactions resulted in a reduction of colonization by 78.7% and 76.0%, respectively, in comparison with the nonmodified control specimens. Particularly, the modified surfaces maintained their antibacterial properties for 3 days, which resulted in the inhibition of biofilm formation . This system offers a biomaterial strategy to effectively prevent biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.

Keywords

3D printing antimicrobial peptide bacterial infection melimine polycaprolactone scaffold

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MeSH Term

Humans
Pseudomonas aeruginosa
Antimicrobial Cationic Peptides
Biofilms
Anti-Bacterial Agents
Coated Materials, Biocompatible
Bacteria
Amino Acids
Carbodiimides
Printing, Three-Dimensional

Chemicals

melimine
polycaprolactone
Antimicrobial Cationic Peptides
Anti-Bacterial Agents
Coated Materials, Biocompatible
Amino Acids
Carbodiimides
Journal Article Research Support, Non-U.S. Gov't

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