4.8 Article

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

Journal

ACS NANO
Volume 16, Issue 10, Pages 16497-16512

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.2c05812

Keywords

bacterial infection; antimicrobial peptide; polycaprolactone; 3D printing; scaffold; melimine

Funding

  1. ARC Industrial Trans-formation Training Centre for Mutiscale 3D Imaging [IC 180100008]
  2. ARC Discovery Project [DP210103342]
  3. Max Planck Queensland Centre

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The study demonstrates that immobilizing melimine on mPCL scaffolds can effectively prevent bacterial infections on implant surfaces and inhibit biofilm formation.
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 h i g h as 30% in intensive care units in developed countries and as h i g h 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-fl i g h t secondary ion mass spectrometry (ToF-SIMS) spectra of melimine-treated surfaces confirmed immobilization of the peptide, as wel l as its homogeneous distribution throughout the scaffold surface. Amino acid analysis showed that melimine covalent and noncovalent immobilization resulted in a peptide density of similar to 156 and similar to 533 ng/cm(2) , 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 Staphylococcus aureus colonization by 78.7% and 76.0%, respectiv e l y , 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 in vitro. This system offers a biomaterial strategy to effectively prevent biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiot i c treatment.

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