UBC Theses and Dissertations
Local delivery of antimicrobial peptides from titanium surface for the prevention of implant-associated infections Kazemzadeh-Narbat, Mehdi
Titanium (Ti) is a key biomedical material extensively used in orthopaedic implants. Prevention of implant-associated infections has been one of the main challenges in orthopaedic surgery. This challenge is further complicated by the concern over the development of antibiotic resistance as a result of using traditional antibiotics for infection prophylaxis. One of the promising alternatives is the family of antimicrobial peptides (AMPs). The present dissertation develops progressive approaches that enable the loading and local delivery of a unique group of cationic antimicrobial peptides through titanium implant surfaces. In the first technique, a thin layer of micro-porous calcium phosphate (CaP) coating was processed by electrolytic deposition onto the surface of titanium as the drug carrier. The AMP-loaded CaP coating was not cytotoxic for MG-63 osteoblast-like cells, and the implants showed high antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria with 10⁶-fold reductions of both bacterial strains within 30 min and ∼92% and ∼77% inhibition of luminescence at 4 h and 24 h, respectively. Second study investigated the in vitro AMP release, antimicrobial performance, and cytotoxicity of a modified Tet213 (HHC36), as well as the in vivo bone growth of AMP loaded into calcium phosphate coated Ti implants in a rabbit model. Burst release during the first few hours followed by a slow and steady release for 7 days was observed. In vivo bone growth study showed that loading of AMP did not impair bone growth onto the implants. In the last study multilayer thin films of titania nanotubes (NT) and CaP coatings were formulated with AMP and were topped with a thin phospholipid film similar to cell membrane. The films were shown to be non-cytotoxic, hydrophilic, with the potential of tuning loading and release kinetics of AMP. The best model describing the AMP release was first-order model. The first two approaches demonstrated a promising method for an early stage peri-implant infection treatment. The last study proposed a technique to improve the kinetics of AMP release and total loaded AMP quantity, and to increase the Ti interfacial strength while maintain the osteconductivity by applying CaP coating.
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