The sustainable release of Vancomycin and its degradation products from nanostructured collagen/hydroxyapatite composite layers

Infections of the musculoskeletal system present a serious problem with regard to the field of orthopaedic and trauma medicine. The aim of the experiment described in this study is to develop a resorbable nanostructured composite layer with the controlled elution of antibiotics. The layer is composed of collagen, hydroxyapatite nanoparticles and Vancomycin hydrochloride (10wt%). The stability of the collagen was enhanced by means of cross-linking. Four cross-linking agents were studied, namely an ethanol solution, a phosphate buffer solution of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide, genipin and nordihydroguaiaretic acid. High performance liquid chromatography was employed so as to characterize the in vitro release rates of the Vancomycin and its crystalline degradation antibiotically inactive products over a 21-day period. The maximum concentration of the released active form of Vancomycin (approximately 265mg/l) exceeded the minimum inhibitory concentration (MIC) up to an order of 17 times without triggering the burst releasing effect. At the end of the experiment the MIC was exceeded by up to 6 times (approximately 100mg/l). It was determined that the modification of collagen with hydroxyapatite nanoparticles does not negatively influence the sustainable release of Vancomycin. The balance of Vancomycin and its degradation products was observed following 14 days of incubation