Novel Controlled Release Of Lysostaphin-loaded Hydroxyapatite/Chitosan Composites

S. aureus is one of the main causes of hematogenous osteomyelitis, the abuse of antibiotics induced the wide emergence of methicillin resistant Staphylococcus aureus (MRSA). Lysostaphin is a new kind of enzyme that can replace classic antibiotics in certain circumstance. In order to achieve controlled release of lysostaphin, a biocompatible drug carrier is needed. Hydroxyapatite is one of the main components of human bones and demonstrates biocompatibility with many tissues. However HA can absorb enzyme and induce the low efficiency of lysostaphin.In this research, different ratios of HA to CS including 80/20,70/30,60/40, 40/60 were prepared using a co-precipitation method. We carried out experiment on material properties, release vitro and biocompatibility test.Multiple analyses were performed to determine the structural and physicochemical properties of the composites, including scanning microscopy, X-ray diffraction, Fourier transform infrared spectroscopy. The results indicated the composites were compacted and the setting time fit the international standard.Vitro release experiment indicated that 60/40 HA/CS composites had the highest efficiency 87.4% and can last for 120h. Compared with the composites, HA alone carried with lysostaphin can only achieve 6.6% release rate. This is evidence that huge loss of activity in the process of release.In biocompatibility test, although 14%wt ZnO indicate good mechanical properties, the composites were not suitable for MC3T3 cells proliferating on its surface. The shape of MC3T3 cells on its surface became spherical which indicated death of the cells, so excessive ZnO is harmful for the growth of the cells. After we change ZnO into CaO, though its compressive strength is lower than ZnO, decent pH of the material can be reached and the composites were proved to be biocompatible.In conclusion, HA/CS composites prepared by co-precipitation method were compacted in structure and showed controlled release of lysostaphin with good biocompatibility. All the results indicate potential application of HA/CS composites loaded with lysostaphin in bone injury and infection.