Abstract

One of the major health problems linked to methicillin-resistant Staphylococcus aureus (MRSA) is severe diabetic foot ulcers (DFU), which are associated with hospital-acquired infections, lower limb amputations and emerging resistance to the current antibiotics. As an alternative, this work aims to develop a biodegradable and biocompatible material with antimicrobial capacity to prevent DFU. This was achieved by producing active polymeric films with metallic nanoparticles dispersed through a polycaprolactone (PCL) dressing. First, the antimicrobial activity of copper oxide nanoparticles (CuONPs) was tested by the microdilution method, selecting the lowest concentration that has an inhibitory effect on MRSA. Then, active PCL films were prepared and characterized in terms of their physicochemical properties, antimicrobial performance, cytotoxicity, genotoxicity and hemocompatibility. Active films had chemical and thermal properties like the ones without the antimicrobial agents, which was confirmed through FTIR, Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) analysis. In relation to antimicrobial activity, active PCL films inhibited MRSA growth when treated with CuONPs at a concentration of 0.07% (w/w). After exposure to the active film extracts, human foreskin fibroblast cells (ATCC® SCRC1041™) (HFF-1) exhibited a cell viability average above 80% for all treatments and no DNA damage was found. Finally, PCL films with 0.07% (w/w) CuONPs proved to be hemocompatible, and none of the films evaluated had red blood cell breakage greater than 5%, being within the acceptable limits established by the International Organization for Standardization ISO 10993-4:2002.

Highlights

  • Staphylococcus aureus constitutes a global health problem due to the variety and complexity of conditions caused in humans, commonly generating superficial skin conditions and lesions, and being causative agents of pathologies such as pneumonia, endocarditis, infections of the nervous system, septic arthritis and generalized infections or sepsis

  • One of the most important problems associated with S. aureus are severe diabetic foot infections, which are related to hospitalization in diabetic subjects and often lead to minor or major lower limb amputation

  • Because of the increase in the number of microorganisms that are resistant to multiple antibiotics, many studies have been carried out to develop new antimicrobial agents that overcome the resistances of these microorganisms [3]

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Summary

Introduction

Staphylococcus aureus constitutes a global health problem due to the variety and complexity of conditions caused in humans, commonly generating superficial skin conditions and lesions, and being causative agents of pathologies such as pneumonia, endocarditis, infections of the nervous system, septic arthritis and generalized infections or sepsis. Several studies have been carried out to characterize silver nanoparticles and to propose mechanisms for its antimicrobial effectiveness [6,7,8], fewer studies have reported the antibacterial activity of copper nanoparticles and their potential as an antimicrobial agent [5,9,10,11] It has been stated by some researchers that copper and copper oxide nanomaterials are mixed with polymeric solutions, in addition to the fact that they have more stable physical and chemical properties and are cheaper to synthetize, while a high degree of bioassimilation has been reported due to the fact that copper is a trace element in most living organisms [12,13,14,15]. With respect to nanoparticles of other metals such as Au and oxides of metals such as FeO and ZnO, these have been studied as antimicrobial agents and biocides, but their disadvantages lie in their high synthesis costs and high instability and the few studies associated with biocompatibility, with the latter being used more in the manufacture of packaging with antimicrobial properties and as nanosensors [13,16,17]

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