Orthopedic implants are increasingly being used to relieve pain, allow rapid fracture healing, and improve both mobility and independence of patients. However, the introduction of foreign material into the human body predisposes it to infection. The treatment of these infections has become very complicated since the orthopedic implants serve as a surface for multiple species of bacteria to grow at a time into a resistant biofilm layer. In fact, the biofilm formation is associated with one of the most severe orthopedic conditions, the implant-associated osteomyelitis (IAO). Treatment of IAO can include surgical debridement, removal of implants and long-lasting antimicrobial therapy. The demand for surgeries meant for implant removal and replacement is continuously increasing, resulting in higher costs for patients, hospitals and healthcare systems. Nonetheless, treatment failure is common. and there is a high risk of re-infection and prolonged use of postoperative antibiotics. Treatment failure rates of IAO have been estimated to range from 41.8 to 58.2 %. IAO may be caused by a variety of microorganism, however, Staphylococcus aureus (S. aureus) is responsible for >80% of these infections. S. aureus can produce a multilayered biofilm embedded within a glycocalyx or slime layer with heterogeneous protein expression throughout. This biofilm plays a key role in bacterial resistance to antibiotics, mainly due to an insufficient drug penetration within the matrix of the biofilm and to the fact that bacteria within the biofilm adopt a dormant lifestyle, which contributes to a poorly response to antibiotics. Considering the increase of antibiotic resistance, the loss of antibiotic efficacy against S. aureus biofilms and the lack of new treatments to avoid infected implant removal, an alternative therapy is urgently needed.
To overcome the burden associated with S. aureus biofilm formation in implants and the drawbacks of conventional therapy, the aim of the following project is to develop nanoparticle-based drug delivery systems to target implant-associated osteomyelitis. The nanoparticles based on biocompatible lipid and polymeric matrix will be designed for an intravenous administration co-delivery of antimicrobial and antifungal agents. The potential of a therapy combining the antifungal caspofungin with fluoroquinolones to improve their activity against S. aureus biofilms was recently reported. Additionally, lately it has been observed that exposure to a mixture of D-amino acids, did not inhibit the growth of S. aureus in shaking culture, targeting only S. aureus biofilms. In this context, D-amino acids synthesized conjugates will be developed and incorporated in the surface of the nanoparticles system to act as target molecules and disrupt the biofilm. The expertise of the researchers involved and the combination of these new insights should lead to an effective treatment that encompasses the disruption of the biofilms and bacteria eradication.