Sustained release of vancomycin from polyurethane scaffolds inhibits infection of bone wounds in a rat femoral segmental defect model
ABSTRACT Infection is a common complication in open fractures that compromises the healing of bone and can result in loss of limb or life. Currently, the clinical standard of care for treating contaminated open fractures comprises a staged approach, wherein the wound is first treated with non-biodegradable antibiotic-laden poly(methyl methacrylate) (PMMA) beads to control the infection followed by bone grafting. Considering that tissue regeneration is associated with new blood vessel formation, which takes up to 6 weeks in segmental defects, a biodegradable bone graft with sustained release of an antibiotic is desired to prevent the implant from becoming infected, thus allowing the processes of both vascularization and new bone formation to occur unimpeded. In the present study, we utilized biodegradable porous polyurethane (PUR) scaffolds as the delivery vehicle for vancomycin. Hydrophobic vancomycin free base (V-FB) was obtained by precipitating the hydrophilic vancomycin hydrochloride (V-HCl) at pH 8. The decreased solubility of V-FB resulted in an extended vancomycin release profile in vitro, as evidenced by the fact that active vancomycin was released for up to 8 weeks at concentrations well above both the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Using PUR prepared from lysine triisocyanate (LTI) (PUR(LTI)), the extended in vitro release profile observed for V-FB translated to improved infection control in vivo compared to V-HCl in a contaminated critical-sized fat femoral segmental defect. The performance of PUR(LTI)/V-FB was comparable to PMMA/V-HCl beads in vivo. However, compared with PMMA, PUR is a biodegradable system which does not require the extra surgical removal step in clinical use. These results suggest that PUR scaffolds incorporating V-FB could be a potential clinical therapy for treatment of infected bone defects.
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- "However, <40% of the D-Trp had been released by 4 weeks, suggesting that degradation of the scaffold may control D- Trp release kinetics at later (>4 weeks) time points. Since the free base form of each D-AA was used in this study, the release kinetics could be increased by using the more soluble hydrochloride as reported previously for vancomycin Ref. . While antibiotic therapy for up to 8 weeks is recommended for effective treatment of MRSA osteomyelitis , the optimal release profile for D-AAs is unknown and thus merits further investigation. "
ABSTRACT: a b s t r a c t Infectious complications of open fractures continue to be a significant factor contributing to non-osseous union and extremity amputation. The persistence of bacteria within biofilms despite meticulous debridement and antibiotic therapy is believed to be a major cause of chronic infection. Considering the difficulties in treating biofilm-associated infections, the use of biofilm dispersal agents as a therapeutic strategy for the prevention of biofilm-associated infections has gained considerable interest. In this study, we investigated whether local delivery of D-Amino Acids (D-AAs), a biofilm dispersal agent, pro-tects scaffolds from contamination and reduces microbial burden within contaminated rat segmental defects in vivo. In vitro testing on biofilms of clinical isolates of Staphylococcus aureus demonstrated that D-Met, D-Phe, D-Pro, and D-Trp were highly effective at dispersing and preventing biofilm formation individually, and the effect was enhanced for an equimolar mixture of D-AAs. Incorporation of D-AAs into polyurethane scaffolds as a mixture (1:1:1 D-Met:D-Pro:D-Trp) significantly reduced bacterial contami-nation on the scaffold surface in vitro and within bone when implanted into contaminated femoral segmental defects. Our results underscore the potential of local delivery of D-AAs for reducing bacterial contamination by targeting bacteria within biofilms, which may represent a treatment strategy for improving healing outcomes associated with open fractures. Published by Elsevier Ltd.Biomaterials 01/2013; · 8.31 Impact Factor
Conference Paper: Electrohydrodynamic pump service life[Show abstract] [Hide abstract]
ABSTRACT: Electrohydrodynamic pump (EHDP) service life test results are presented. EHDP head and conduction current decrease is established. The degradation of EHDP indices can be the result of electrochemical reaction products and mechanical impurity deposition on the electrodes. It is concluded that EHDP service life can be very long if the following conditions are met: absence of mechanical impurities in the working liquid; liquid chemical stability under electric breakdown; and the use of liquids which do not exhibit colloidal particle formation as a result of electric field effect in the presence of gases, water, and EHDP part materialsConduction and Breakdown in Dielectric Liquids,1993., ICDL '93., IEEE 11th International Conference on; 08/1993
- Journal of the American College of Cardiology 04/2011; 57(14). DOI:10.1016/S0735-1097(11)60039-9 · 15.34 Impact Factor