The Sustainable Release of Vancomycin and Its Degradation Products from Collagen/Hydroxyapatite Nano/Micro Structured Layers Prepared using Different Techniques

Tomas Suchy

Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague

Tomas Suchy received his M.S. degree in Biomedical and Rehabilitation Engineering, and a Ph.D. degree in Biomechanics from the Czech Technical University in Prague, Czech Republic, in which his research was focused on composite materials. He is now a head of the Department of Composites and Carbon Materials at the Institute of Rock Structure and Mechanics, Czech Academy of Sciences. He also works as assistant professor at Department of Mechanics, Biomechanics and Mechatronics, Faculty of Mechanical Engineering, Czech Technical University in Prague. His research focuses on biocomposite materials and bone tissue engineering.

Abstract

Introduction
Infections of the musculoskeletal system present a serious challenge in the field of orthopaedic and trauma medicine. The aim of the experiment was to develop a resorbable layer via the controlled elution of antibiotics to be used as a bone/implant bioactive interface particularly in the case of prosthetic joint infections or as a preventative procedure regarding primary joint replacement in a potentially infected site.

Methods
Nano- or micro-structured layers based on collagen (type I, VUP Medical, Czech Republic) and 0, 5 or 15wt% of hydroxyapatite nanoparticles (avg. 150nm, Sigma Aldrich, Germany) were prepared employing the lyophilisation or electrospinning of dispersions with or without 10wt% vancomycin hydrochloride (Mylan S.A.S, France) and subsequently cross-linked by EDC/NHS (Sigma Aldrich, Germany). Pure cross-linked collagen/hydroxyapatite electrospun mats were subsequently impregnated with 10wt% vancomycin. The in vitro release rates of vancomycin and its inactive degradation products were characterized by HPLC. The antimicrobial effects of the layers were determined using agar diffusion testing against four different clinical isolates. The in vitro biological evaluation was conducted using SAOS-2 cells in direct contact with the layers or 24h infusions (MTS/LDH tests).

Results
The maximum concentration of the released active form of vancomycin (700mg/l after 3hours, 150mg/l 21stday) was assessed by means of the vancomycin impregnation of cross-linked electrospun layers. The lowest concentration was determined for those layers electrospun directly from a collagen solution with vancomycin. Agar diffusion tests revealed that the electrospun impregnated layers exhibited the highest activity. Modification using hydroxyapatite exerts no strong effect on vancomycin evolution. All the tested samples showed a sufficient cytocompatibility rate with no indication of cytotoxic effects.

Discussion
The higher specific surface of nanostructured layers probably plays a negative role in the preparation process due to the higher rate of vancomycin elution to the cross-linking solution. This may be overcome via the subsequent impregnation of the cross-linked layers. Our results suggest that the local application of high-dose vancomycin via drug delivery carriers provides a safe therapeutic osteomyelitis treatment method that prevents the development of bacterial resistance.

Acknowledgments
This study was supported by the Technology Agency of the Czech Republic (project no. TA04010330).

Authors

Tomas Suchy (Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague)
Monika Supova (Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague)
Eva Klapkova (Department of Medical Chemistry and Clinical Biochemistry, Charles University, 2nd Medical School and University Hospital Motol, Prague)
Vaclava Adamkova (Clinical microbiology and ATB centre, Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague)
Jan Zavora (Clinical microbiology and ATB centre, Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague)
Margit Zaloudkova (Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague, Czech Republic)
Martin Braun (Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague)
Rastislav Ballay (1st Department of Orthopaedics, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague)
Frantisek Denk (Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague)
Jiri Rebicek (Contipro Biotech s.r.o., R&D Department, Dolni Dobrouc)
Marek Pokorny (Contipro Biotech s.r.o., R&D Department, Dolni Dobrouc)
Pavla Sauerova (Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University in Prague, Ke Karlovu 2, Prague)
Marie Hubalek Kalbacova (Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University in Prague, Ke Karlovu 2, Prague)
Lukas Horny (Faculty of Mechanical Engineering, Czech Technical University in Prague, Prague)
Jan Vesely (Faculty of Mechanical Engineering, Czech Technical University in Prague, Prague)
Tereza Vonavkova (Faculty of Mechanical Engineering, Czech Technical University in Prague, Prague)

Topic Areas

Targeted drug delivery and Nanocarriers , Tissue engineering and regenerative nanomedicine

Session

OS3-101 » Tissue engineering and regenerative nanomedicine (16:00 - Friday, 30th September, Tower 24 - Room 101)

Presentation Files

The presenter has not uploaded any presentation files.

Email Support • Blog • Privacy Policy • Cancellation Policy