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Bio-inspired AntiMicrobial Bone BIoceramics: Deciphering contact-based biocidal mechanisms

Periodic Reporting for period 1 - BAMBBI (Bio-inspired AntiMicrobial Bone BIoceramics: Deciphering contact-based biocidal mechanisms)

Periodo di rendicontazione: 2022-12-01 al 2025-05-31

Bone infections, that result in bone destruction, are one of the great challenges of orthopaedic and maxillofacial surgery. The first line of treatment is the administration of antibiotics. But they are often unable to eradicate the infection. In addition, prolonged treatments increase the likelihood of favoring the selection of bacteria resistant to antibiotics. Antibiotic resistance kills more than 1 million people each year worldwide and has become a global health threat. This calls for radically novel alternatives that are not based on antibiotics to combat microbial infections.
Moreover, when a tissue becomes infected, besides getting rid of the infection it is also necessary to rebuild the damaged tissue. In the case of bone, antimicrobial bone substitutes have been suggested, but most of them rely on the release of chemical agents such as antibiotics. However, this only works for short periods of time and faces the problem of antibiotic resistance.
BAMBBI aims to tackle this challenge by developing synthetic materials based on calcium phosphates that can prevent or even fight infections while simultaneously promoting bone regeneration, without the use of antibiotics. Our proposed strategy is based on the recent discovery that some natural surfaces are capable of killing bacteria by contact. This is possible because these surfaces have a special structure, with tiny protrusions (what we call nanotopography), as small as the bacteria themselves. However, it is hard to fabricate such small nanostructures, and so far they have only been developed on a limited number of materials. Our goal is to develop this kind of bactericidal surfaces in materials that can be used in real 3D implants, such as synthetic bone grafts, that can be used in medical practice.
Moreover, BAMBBI aims to better understand how different types of bacteria react to the nanotopography and surface chemistry of materials when they come into contact with them. In this way, it aims to identify the underlying causes of significant variations in the bactericidal efficacy of a given substrate for different bacterial strains. By addressing these scientific questions, the BAMBBI project aims to design more effective antibacterial implants that can regenerate bone more efficiently, even in the presence of bacterial infections.
The approach used to develop antimicrobial topographies in synthetic bone substitutes is again inspired by nature. Nature uses different strategies to generate biominerals with complex shapes and structures by precipitation from aqueous solutions. These include the modification of reaction conditions and the presence of soluble additives, such as crystallisation modifiers, inhibitors or nucleation agents. In the project, we have already demonstrated the potential of this strategy for the development of calcium phosphate nanotopographies with antimicrobial properties. By controlling how calcium phosphate crystals form and grow, playing with the reaction conditions and the interaction with ions and organic molecules, the surface morphology of calcium phosphate 3D implants can be tailored. We have developed calcium phosphate surfaces consisting of tiny nanopillars that are able to kill bacteria by contact. Moreover, we will further explore the possibility of enhancing the capacity of killing bacteria by modifying the chemical nature of the surface. All these strategies allow us to study in detail how bacteria are killed by contact and what role nanotopography (the structure of the surface) and surface chemistry play in this process.
BAMBBI has the ambitious goal of creating antimicrobial surfaces on real bone grafting biomaterials. In contrast to the antimicrobial nanostructures developed so far, the contact-killing topographies are to be produced not on inert surfaces but on substrates that are bioactive and thus capable of promoting bone formation. The impact of the development of materials with antimicrobial properties and, even more so, of the knowledge of the fundamental mechanisms of action is enormous, given the interest that antimicrobial materials have in fields as diverse as food and medical packaging, surgical instrumentation, and water remediation, among others. Moreover, beyond the antimicrobial properties, the accurate control of the nanostructure of calcium phosphate materials is expected to have a great impact in a wide range of fields where calcium phosphates find application, such as catalysis for chemical reactions and environmental sciences, water purification and protein separation.
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