Author: Sunjung Kim
Publisher:
Published: 2020
Total Pages: 0
ISBN-13:
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The use of antibiotic-loaded bone cement is an established method in the management of periprosthetic hip and knee joint infection. Despite inconsistencies among published studies, mechanical failure and infection are leading causes of failure in early revisions (15.7% and 8.2% for hip; 21% and 7.9% for knee). This study evaluates the effect of antibiotics on mechanical properties, antibacterial properties, and release characteristic when incorporated into the bone cement. These data are needed as a benchmark for the next generation of new antibiotic loaded bone cements and also can be used to develop new formulations. Chapter 3 (Manuscript #1) investigated the mechanical properties of a commercially available bone cement with the addition of vancomycin, to determine the release characteristics and efficacy at eliminating the orthopedic implant pathogens. Palacos®ʼ R was loaded with incrementally larger clinically relevant weight percentages of vancomycin. The addition of vancomycin reduced the bone cement's mechanical properties. Also, vancomycin eluted from Palacos®ʼ R with a steady rise in eluted volume up to 8 days, after which non-therapeutic elution concentrations were observed up to a 60-day end point. The eluted concentration from samples with greater than 0.25 g vancomycin per Palacos®ʼ R packet was sufficient to eliminate a 103 colony forming unit per mL (CFU/mL) initial inoculum of S. aureus, including methicillin-resistant S. aureus (MRSA). Chapter 4 (Manuscript #2) investigated SimplexTM P, a commercially available bone cement with vancomycin. Vancomycin at five different loading masses (0.125, 0.25, 0.5, 1.0 and 2.0 g) was added to 40 grams of SimplexTM P. Addition of vancomycin affected the mechanical properties and antimicrobial activity with significant differences from controls. Flexural and compression mechanical properties were compromised with added vancomycin. The flexural strength of samples with added vancomycin of 0.5 g and greater were not greater than ISO 5833 minimum requirements. 2.0 g of vancomycin added to bone cement was able to eliminate completely the four bacterial strains tested. 2.0 g of vancomycin also showed the highest mass elution from the cement over a 60-day period. Given the reduced flexural strength in samples with 0.5 g and greater of added vancomycin and the inability of vancomycin in amounts less than 2.0 g to eliminate bacteria, this study did not find an ideal amount of vancomycin added to SimplexTM P that meets both strength and antibacterial requirements. Chapter 5 (Manuscript #3) evaluated telavancin elution, stability, and antimicrobial activity when incorporated into the commercial bone cements Palacos℗ʼ R and SimplexTM P. Telavancin at five loading volumes (0.3 vol%, 0.6 vol%, 1.2 vol%, 2.4 vol%, and 4.8 vol%). was added to the two cements. The release characteristics of telavancin were recorded for 60 days to estimate the elution profiles. The efficacy of eluted telavancin for eliminating four common implant pathogens was determined. Mechanical testing was also performed. Telavancin affected the elution, antimicrobial activity, and mechanical properties in a dose-dependent manner. Telavancin added to Palacos®ʼ R at 4.8 vol% was able to eliminate MSSA, MRSA, and S. epidermidis, while the same concentration in SimplexTM P failed to kill all tested strains. Telavancin also exhibited better elution in the former case over a 60-day period. Both cements showed reduced flexural and compression properties with added telavancin. Telavancin loaded to Palacos®ʼ R achieved better efficacy than in SimplexTM P. Under microscopic examination the two cements showed different numbers and size of pores, potentially affecting strength. Telavancin loaded in Palacos℗ʼ R is a promising prophylactic option. However, the feasibility of using telavancin as an alternative to traditional antibiotics in acrylic bone cement requires further consideration due to the unsustained telavancin release and reduced strength. Chapter 6 (Manuscript #4) was a computational investigation of the effect of porosity and its distribution on bone cement fracture toughness. The effect of pores was analyzed using the extended finite element method (X-FEM) crack propagation simulation method with different sizes of pores and locations. Predicted force-displacement behavior and fracture toughness were compared to experimental results. Crack growth and propagation are affected by porosity parameters, for example, pore size an independent parameter and dependent parameters such as pore-pore and pore-crack interactions. These dependent porosity parameters are primarily affected by pore size and pore location. The experimental and simulation results of the current study contribute to a better understanding of the effect of porosity on bone cement fracture toughness.
