The aim of the study was to develop an orthopedic implant coating in the form of vancomycin-loaded collagen/hydroxyapatite layers (COLHA+V) that combine the ability to prevent bone infection with the ability to promote enhanced osseointegration. The ability to prevent bone infection was investigated employing a rat model that simulated the clinically relevant implant-related introduction of bacterial contamination to the bone during a surgical procedure using a clinical isolate of Staphylococcus epidermidis. The ability to enhance osseointegration was investigated employing a model of a minipig with terminated growth. Six weeks following implantation, the infected rat femurs treated with the implants without vancomycin (COLHA+S. epidermidis) exhibited the obvious destruction of cortical bone as evinced via a cortical bone porosity of up to 20% greater than that of the infected rat femurs treated with the implants containing vancomycin (COLHA+V+S. epidermidis) (3%) and the non-infected rat femurs (COLHA+V) (2%). The alteration of the bone structure of the infected COLHA+S. epidermidis group was further demonstrated by a 3% decrease in the average Ca/P molar ratio of the bone mineral. Finally, the determination of the concentration of vancomycin released into the blood stream indicated a negligible systemic load. Six months following implantation in the pigs, the quantified ratio of new bone indicated an improvement in osseointegration, with a two-fold bone ingrowth on the COLHA (47%) and COLHA+V (52%) compared to the control implants without a COLHA layer (27%). Therefore, it can be concluded that COLHA+V layers are able to significantly prevent the destruction of bone structure related to bacterial infection with a minimal systemic load and, simultaneously, enhance the rate of osseointegration.

1st Department of Orthopedics 1st Faculty of Medicine Charles University Prague and Motol University Hospital 150 06 Prague 5 Czech Republic

2nd Department of Cardiovascular Surgery 1st Faculty of Medicine Charles University and General University Hospital Prague 12000 Prague 2 Czech Republic

Biomedical Center Faculty of Medicine in Pilsen Charles University 30100 Pilsen Czech Republic

Department of Composites and Carbon Materials Institute of Rock Structure and Mechanics Czech Academy of Sciences 18209 Prague 8 Czech Republic

Department of Histology and Embryology Faculty of Medicine in Pilsen Charles University 301 00 Pilsen Czech Republic

Department of Medical Chemistry and Clinical Biochemistry Charles University 2nd Medical School and University Hospital Motol 15006 Prague 5 Czech Republic

Faculty of Mechanical Engineering Czech Technical University Prague 16000 Prague 6 Czech Republic

Institute of Anatomy 1st Faculty of Medicine Charles University 12000 Prague 2 Czech Republic

Institute of Dental Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague 12000 Prague 2 Czech Republic

PIGMOD Centre Laboratory of Cell Regeneration and Plasticity Institute of Animal Physiology and Genetics Czech Academy of Sciences 27721 Libechov Czech Republic

ProSpon Ltd 27201 Kladno Czech Republic

R and D Department Contipro Inc 56102 Dolni Dobrouc Czech Republic

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