In vivo efficiency of antimicrobial inorganic bone grafts in osteomyelitis treatments

• Published in: Materials Science & Engineering C Vol. 97; pp. 84 - 95
• Main Authors: Mestres, G., Fernandez-Yague, M.A., Pastorino, D., Montufar, E.B., Canal, C., Manzanares-Céspedes, M.C., Ginebra, M.P.
• Format: Journal Article Publication
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2019; Elsevier BV; Elsevier
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Antibiotics; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Biocompatibility; Biomaterials; Biomedical materials; Bone Cements - chemistry; Bone Cements - pharmacology; Bone Diseases, Infectious - drug therapy; Bone Diseases, Infectious - therapy; Bone grafts; Bone growth; Bone Regeneration - drug effects; Calcium; Calcium phosphate cements; Calcium phosphate foams; Calcium phosphates; Calcium Phosphates - chemistry; Cements; Composite materials; Containment; Doxycycline; Doxycycline - administration & dosage; Doxycycline - pharmacology; Drug delivery; Drug Delivery Systems - methods; Drug Implants - chemistry; Drug Implants - pharmacology; Drug Liberation; Engineering Science with specialization in Materials Science; Enginyeria biomèdica; Female; Femur; Femur - diagnostic imaging; Femur - pathology; Foams; Grafts; Health; Implants artificials; Implants, Artificial; In vivo; In vivo methods and tests; Infections; Macroporosity; Magnesium; Magnesium phosphate; Magnesium phosphate cements; Materials biomèdics; Materials science; Microporosity; Osteomyelitis; Osteomyelitis - drug therapy; Osteomyelitis - therapy; Parameters; Porosity; Rabbits; Regeneration; Regeneration (physiology); Staphylococcal Infections - drug therapy; Staphylococcal Infections - therapy; Statistical analysis; Structural integrity; Substitute bone; Surgical implants; Teknisk fysik med inriktning mot materialvetenskap; Treatment Outcome; Viscoelastic Substances - chemistry; Àrees temàtiques de la UPC; Osteomyelitis; Magnesium phosphate cements; In vivo; Drug delivery; Calcium phosphate cements; Calcium phosphate foams
• ISSN: 0928-4931; 1873-0191; 1873-0191
• DOI: 10.1016/j.msec.2018.11.064

The purpose of the present work was to evaluate in vivo different antimicrobial therapies to eradicate osteomyelitis created in the femoral head of New Zealand rabbits. Five phosphate-based cements were evaluated: calcium phosphate cements (CPC) and calcium phosphate foams (CPF), both in their pristine form and loaded with doxycycline hyclate, and an intrinsic antimicrobial magnesium phosphate cement (MPC; not loaded with an antibiotic). The cements were implanted in a bone previously infected with Staphylococcus aureus to discern the effects of the type of antibiotic administration (systemic vs. local), porosity (microporosity, i.e. <5 μm vs. macroporosity, i.e. >5 μm) and type of antimicrobial mechanism (release of antibiotic vs. intrinsic antimicrobial activity) on the improvement of the health state of the infected animals. A new method was developed, with a more comprehensive composite score that integrates 5 parameters of bone infection, 4 parameters of bone structural integrity and 4 parameters of bone regeneration. This method was used to evaluate the health state of the infected animals, both before and after osteomyelitis treatment. The results showed that the composite score allows to discern statistically significant differences between treatments that individual evaluations were not able to identify. Despite none of the therapies completely eradicated the infection, it was observed that macroporous materials (CPF and CPFd, the latter loaded with doxycycline hyclate) and intrinsic antimicrobial MPC allowed a better containment of the osteomyelitis. This study provides novel insights to understand the effect of different antimicrobial therapies in vivo, and a promising comprehensive methodology to evaluate the health state of the animals was developed. We expect that the implementation of such methodology could improve the criteria to select a proper antimicrobial therapy. [Display omitted] •Antibiotic-loaded calcium phosphates cements were used for osteomyelitis treatment.•Macroporous calcium phosphates showed better performance in vivo than microporous ones.•Microporous magnesium phosphates cements had intrinsic antimicrobial activity in vivo.•A composite score provides a comprehensive evaluation of the animals' health state.