Novel silver-functionalized poly(εcaprolactone)/hydroxyapatite biomaterials designed to counteract post-surgical infections.

Introduction: In surgery, device implantation establishes a non-negligible incidence of infections, representing one of the major causes of morbidity and mortality in this medical field. A foreign body presence is the triggering event for biomaterial-associated infections (BAIs), because biomaterial surface and roughness not only attract host eukaryotic cells involved in tissue regeneration, but also free-floating bacteria. Indeed, as soon as a contamination occurs, the “race to the surface” begins, determining the fate of infection development. These concerns led to the exploration of synthetic biodegradable polymers, such as poly (ε-caprolactone) (PCL), a hydrophobic bioresorbable material with a great potential in biomedical applications, either as a porous scaffold in bone tissue reconstruction or as vehicle for controlled delivery of therapeutic molecules. Aim of the present research is the development of novel PCL-based biomaterials, modified with both hydroxyapatite (HA), to impart bioactive/bioresorbable properties, and silver, to supply antibacterial behavior. Therefore, the designed scaffold will be able to promote fast and physiological bone integration and avoid bacterial contamination. Materials and methods: PCL and HA/PCL porous pellets, functionalized with silver ions (Ag+) were developed by salt-leaching methods, sieved in the range 125-355 m, as a pore former. Samples were further characterized from the chemical and morphological point of view. Antibacterial tests were performed by assaying Staphylococcus aureus adhesion on biomaterials through a sonication protocol to dislodge adherent microorganisms without altering their viability. The planktonic bacteria number was also determined. Results: Field Emission Scanning Electron Microscopy showed that the samples were characterized by square-shaped macropores, whose average dimension was in agreement with that of the starting salt. X-Ray Diffraction analysis confirmed the presence of PCL and HA phases, while Energy Dispersive X-ray Diffraction confirmed the presence of Ag in the correct amount. The antibacterial tests revealed a significant (p<0.001) reduction of the adherent staphylococci on the Ag-functionalized surfaces, after 24 h of incubation, with values of about 104/103 CFU/ml respect to109 CFU/ml for controls. Additionally, a similar significant (p<0.001) decrease in CFU/ml was also detected for planktonic bacteria, thus proving the Ag release from the enriched PCL-based samples. Discussion and Conclusions: Due to the combined antimicrobial and biodegradable properties, the PCL-based scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy, as an ideal microbial anti-adhesive tool, for the reduction in BAIs and antimicrobial molecules-targeted delivery.