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

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 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%, 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 in vitro. This system offers a biomaterial strategy to effectively prevent biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.

X‐Ray Techniques Dedicated to Materials Characterization in Cultural Heritage

“…[65] A limitation of the XPS method is the lack of molecular specificity. [78] 2.4. X-ray absorption fine structure (XAFS)…”

“…The quantitative measurements are affected by the peak intensity, accuracy of the relative sensitivity factor, surface volume homogeneity, signal‐to‐noise ratio, correction for the energy dependence of electron mean free path, correction for the electron transmission function, and degree of the sample degradation [65] . A limitation of the XPS method is the lack of molecular specificity [78] …”

Probing the Effects of Antimicrobial‐Lysozyme Derivatization on Enzymatic Degradation of Poly(ε‐caprolactone) Film and Fiber

“…[1][2][3] According to current estimates, about 4-10% of implant surfaces are contaminated with bacteria from various sources, while the infection rate in intensive care units is estimated to be as high as 30-45%. [4,5] The alarming statistics emphasize the importance of developing strategies to render the DOI: 10.1002/mabi.202300296 implant surfaces free of infection to improve patient outcomes. [6,7] Further, the increasing prevalence of antimicrobial resistance has greatly diminished the effectiveness of antibiotic-based treatment protocols for infections caused by multidrug-resistant and extensively resistant strains.…”

“…For instance, Cometta et al functionalized the surface of 3D-printed poly(𝜖-caprolactone) (PCL) with an antimicrobial peptide, melimine, and demonstrated its ability to substantially decrease bacterial viability and biofilm formation. [5] Similarly, Lin et al demonstrated PCL encapsulated with HHC36, a synthetic antimicrobial peptide, as a coating option to mitigate catheter-associated urinary tract infections. [20] Among several natural antimicrobial substances, lysozyme is known to be the first line of defense that imparts innate immunity to the host against a wide spectrum of pathogens with high efficacy and biocompatibility.…”

“…functionalized the surface of 3D‐printed poly(ε‐caprolactone) (PCL) with an antimicrobial peptide, melimine, and demonstrated its ability to substantially decrease bacterial viability and biofilm formation. [ 5 ] Similarly, Lin et al. demonstrated PCL encapsulated with HHC36, a synthetic antimicrobial peptide, as a coating option to mitigate catheter‐associated urinary tract infections.…”