The BBT research group has a solid experience in the development of biomaterials for bone and cardiovascular applications. In detail, our group has focused on surface modifications at the physical and chemical level to achieve either antibacterial, osteoinductive or proendothelialization properties. However, in a clinical context the complex process of implant biointegration is limited by bacterial infections and thrombogenicity, which affect bone and endothelial tissue healing, respectively. Thus, to adequately address these problems, a combined effect is required. Therefore, the aim of the present subproject will be focused on the investigation of novel biomaterials coatings with dual-action capacities: osteoconductive/inductive and antimicrobial, for bone; and pro-endothelialization and anti-thrombogenic properties, for cardiovascular applications. To this end, the following strategies will be established: A. Development of biocompatible and biodegradable zinc alloys with controlled degradation rate and mechanical properties. This approach will eliminate the long-term health risks associated to permanent implants, such as thrombosis, and enhance tissue healing. B. Design and fabrication of novel antimicrobial coatings with combined bactericidal molecules to i) reduce the induction of bacterial resistance, and ii) achieve a synergistic antibacterial action. This strategy will combine metallic nanoparticles conjugated with antibiotics (amikacin or colistin), antimicrobial peptides (e.g. hLf1-11 peptide), antimicrobial silanes (TEPSA) or inhibitory molecules of bacterial quorum sensing. C. Development of novel coatings with osteoinductive (integrin-selective peptidomimetics; recombinant protein fragments, gallium ions) and antimicrobial properties (strategies B) to engineer biomaterials with improved osteointegrative and anti-infective capacity. D. Investigation of novel biomaterials with both anti-thrombogenic (PEG, heparin-based drug release) and pro-endothelialization (peptidebased platforms with YIGSR) properties will favour the formation of a healthy and functional endothelium. The dual-action coatings will be carefully characterized by means of a wide range of mechanical and physicochemical methods, in vitro static and dynamic studies, with a bioreactor, of cellular response (adhesion, proliferation, migration and differentiation), antibacterial properties and thrombogenicity tests. The in vivo bacterial response of the most promising coatings will be performed in an animal model of foreign body with RjOrl: SWISS mice. To address the anti-thrombogenic and endothelialization effects of the biomaterials for cardiovascular applications, a model of aorta with Wistar rats will be performed. The combination of dual-action coatings together with biodegradable metal implants will serve to develop new implants with the ability to overcome bacterial infection or thrombosis, a goal that falls within the main strategies described in the PLAN ESTATAL DE INVESTIGACIÓN CIENTÍFICA Y TÉCNICA Y DE INNOVACIÓN 2017-2020.
Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020
Programa Estatal de I+D+i Orientada a los Retos de la Sociedad