Calcium pHosphates mAterials with Nature inspired baCtEricidal surface: towards a non-antibiotic approach to treat bone infection

Principal investigator: Michele Iafisco

Starting date: 28/09/2023
Duration: 24 month
CNR-ISSMC role: Coordinator
Coordinator: Michele Iafisco (CNR-ISSMC)
Consortium: Consiglio Nazionale delle Ricerche (CNR-ISSMC e CNR-SCITEC); Università Cattolica del Sacro Cuore

Bacterial bone infections (osteomyelitis) are nowadays one of the most serious problems associated to orthopedic surgery. Osteomyelitis is usually treated by surgical removal of the infected bone followed by a massive intravenous administration of broad-spectrum antibiotics. Unfortunately, the efficacy of this therapy is low and is compounded by the emergence of antibiotic resistant bacteria. This issue calls for urgent alternatives to fight bone infection that are not based on antibiotics. The discovery of the bactericidal properties of some natural surface topographies has opened a new avenue of research, emphasizing the concept of bio-instructive materials. This effect is governed by surface geometrical features at nanometric level, which have the capacity to mechanically rupture bacteria membrane upon contact. Great efforts have been made to transfer this property to synthetic materials. However, despite the progress made, there are still many unanswered questions, and biocidal nano-topographies were produced only on inert substrates that are not bioactive. In fact, in the case of osteomyelitis the therapeutic approach requires not only eradicating the infection, but simultaneously regenerating the destroyed bone using graft materials. CHANCE aims to address all these challenges by generating nanostructured surfaces with high-aspect ratio that can kill bacteria by contact onto bioactive and osteo-inductive synthetic calcium phosphate which represents the best biomaterial as bone graft substitute. This will be achieved by a fine control of nano-topography, using a novel bottom-up approach inspired by biomineralization routes, harnessing the influence of organic molecules and ions to drive crystal nucleation and growth of inorganic materials. Moreover, CHANCE aims to further enhance the biocidal effect of the materials through the surface functionalization with antimicrobial peptides. In this way a biochemical antimicrobial mechanism will be superimposed on the mechanical antimicrobial action of surface topography. Antimicrobial peptides are produced in all kinds of organisms as components of the innate immune system. They have a broad spectrum of action and, differently from antibiotic drugs, act by different mechanisms against which bacteria hardly develop resistance. Finally, we aim also to improve our knowledge about the molecular mechanisms of bacteria-surface interactions through the complete evaluation of proteomic and genomic signature of pathogens in contact with the biocidal surfaces. The success of our approach will pave the way to the development of more efficient devices that are simultaneously bioactive and bactericidal. CHANCE is multidisciplinary and 2 research units (Consiglio Nazionale delle Ricerche and Università Cattolica del Sacro Cuore) with different and complementary expertise including chemistry, material sciences, microbiology, cell biology, and biochemistry, are involved for the achievement of the overall goal.