ABSTRACT
A degradable, poly (lactic-co-glycolic acid) (PLGA), gentamicin-loaded prophylactic coating for hydroxyapatite (HA)-coated cementless hip prostheses is developed with similar antibacterial efficacy as offered by gentamicin-loaded cements for fixing traditional, cemented prostheses in bone. We describe the development pathway, from in vitro investigation of antibiotic release and antibacterial properties of this PLGA-gentamicin-HA-coating in different in vitro models to an evaluation of its efficacy in preventing implant-related infection in rabbits. Bone in-growth in the absence and presence of the coating was investigated in a canine model. The PLGA-gentamicin-HA-coating showed high-burst release, with antibacterial efficacy in agar-assays completely disappearing after 4 days, minimising risk of inducing antibiotic resistance. Gentamicin-sensitive and gentamicin-resistant staphylococci were killed by the antibiotic-loaded coating, in a simulated prosthesis-related interfacial gap. PLGA-gentamicin-HA-coatings prevented growth of bioluminescent staphylococci around a miniature-stem mounted in bacterially contaminated agar, as observed using bio-optical imaging. PLGA-gentamicin-HA-coated pins inserted in bacterially contaminated medullary canals in rabbits caused a statistically significant reduction in infection rates compared to HA-coated pins without gentamicin. Bone ingrowth to PLGA-gentamicin-HA-coated pins, in condylar defects of Beagle dogs was not impaired by the presence of the degradable, gentamicin-loaded coating. In conclusion, the PLGA-gentamicin-HA-coating constitutes an effective strategy for infection prophylaxis in cementless prostheses.
Subject(s)
Coated Materials, Biocompatible/pharmacology , Durapatite/chemistry , Gentamicins/pharmacology , Hip Prosthesis , Prosthesis-Related Infections/prevention & control , Staphylococcal Infections/prevention & control , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Bone Cements , Bone Nails , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacokinetics , Dogs , Drug Resistance, Bacterial/drug effects , Female , Femur/surgery , Gentamicins/chemistry , Gentamicins/pharmacokinetics , Lactic Acid/chemistry , Male , Microscopy, Electron, Scanning , Osseointegration/drug effects , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Prosthesis-Related Infections/microbiology , Rabbits , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/physiology , Treatment OutcomeABSTRACT
Push-out testing is frequently used to assess the interfacial shear strength developed at a bone-biomaterial interface during in vivo experiments. The aim of the present research was to assess the in vivo performance of a novel substrate/coating combination and to introduce a more rigorous fracture mechanics analysis of the push-out test data. An adhesively bonded hydroxyapatite (HA), and a Ti-6Al-4V alloy plasma sprayed with HA, were implanted in female New Zealand white rabbits for up to 6 months in duration. After death, push-out tests were carried out and the shear strength was calculated in the conventional way, together with microscopical examination of crack paths. A finite element model was drawn up representing four potential failure mechanisms. The measured "failure shear strengths" in conventional analysis were approximately equal for the two coatings. However, JC at failure calculated from the model was 210 J m(-2) at the novel adhesively bonded HA/bone interface and 5 J m(-2) at a conventional titanium/plasma-sprayed HA interface. The conventional shear strength approach is strongly test dependent, and we believe that the fracture energy approach represents a more rigorous analysis of the real failure criterion in the implant/host tissue structure.
ABSTRACT
Samples of collagen were cross-linked by two different methods: (a) glutaraldehyde and (b) a combination of dehydrothermal treatment and cyanamide. The elastic modulus, the ultimate tensile strength (fracture stress), strain to failure, work of fracture, and fracture toughness were measured before and after cross-linking in ambient laboratory conditions, and during immersion in water. These tests were all performed over a range of strain rates. For collagen tested in the wet condition, it was found that cross-linking increased the elastic modulus from approximately 25-30 MPa, to between 55 and 60 MPa, but there was little effect on fracture stress, and strain to failure was reduced. The work of fracture of the collagen decreased on cross-linking. Cross-linking had the same effect on the elastic modulus, fracture stress, and strain to failure of dry collagen, but the work of fracture was unaffected. In conclusion, cross-linking increased the elastic modulus, reduced the strain to failure, and had little effect on the fracture stress of collagen under the present experimental conditions.
Subject(s)
Biocompatible Materials , Collagen/chemistry , Biomechanical Phenomena , Cross-Linking Reagents , Elasticity , Materials Testing , Stress, Mechanical , Structure-Activity RelationshipABSTRACT
Four patients with pulmonary blastomycosis are reported. Their bronchial washings, submitted for cytologic evaluation and stained by the standard Papanicolau technique, yielded the diagnosis, subsequently confirmed by cultural identification of the fungus. In three additional cases, retrospective evaluation of cytologic material also revealed the organism, even though the diagnostic significance was not appreciated originally. Since cytologic techniques are simple, readily available, and rapid, they can be helpful in differentiating pulmonary neoplasms from pulmonary blastomycosis, thus reducing the need for diagnostic thoracotomies.
