Biomaterial Approaches for the Treatment and Prevention of Orthopaedic Infections

Bone infection is a dreaded complication in orthopedic trauma surgery which can severely delay or prevent successful patient recovery. Due to impaired vascularity at the trauma site, systemic antibiotic therapies are limited in their capacity to clear the local infection. Local antibiotics are required to improve outcome of infection treatment, with antibiotic loaded bone cements or collagen sponges being frequently utilized in clinics. However, these materials are associated with unfavorable characteristics such as inappropriate antibiotic release kinetics or non-biodegradability. This thesis reports on the development of biomaterials for implementation as local antibiotic delivery systems for treatment or prevention of orthopedic infections. Biodegradable microspheres have been developed which can be efficiently loaded with hydrophobic antibiotics and their surfaces can be subsequently functionalized with bone targeting molecules. This approach yielded promising in vitro results leading to enhanced antibiotic delivery to mineralized substrates. As antibiotic resistance becomes an increasingly troublesome complication in infection treatment, delivery of alternative and effective antimicrobials to infected bone tissue is becoming an urgent clinical need. Bacteriophages were embedded in a thermoresponsive hydrogel system and these hydrogels allowed for sustained antibiotic release over a 3-week period. Bacteriophage lytic activity and release kinetics could be improved by incorporation of alginate based microbeads into the hydrogels. Biofilm formation on orthopedic devices also contribute to treatment failure of antimicrobial treatments. Due to the impaired immune response on the Summary 262 device interface, these surfaces are susceptible to bacterial adhesion and biofilm formation which can lead to persisting infections. Hydrophilic antifouling coatings and cationic bactericidal coatings were introduced in this thesis, and showed that in an in vitro set-up adhesion of viable bacteria could be synergistically reduced when both coatings were applied to poly(ether ether ketone) surfaces. These anti-fouling and antimicrobial surfaces can slow the process of device colonization, allowing prophylactic antibiotics sufficient time to prevent the development of a device-related infection. This thesis is comprised of the development of multiple biomaterials designed for antimicrobial strategies to treat or prevent bone infection. Enhanced antibiotic delivery was achieved by designing bone targeting microspheres. Additionally, common complications such as antibiotic resistance and device-related infection have been addressed with new treatment solutions that should be further developed in pre-clinical models.