ABSTRACT
@#Introduction: This study aims to investigate different residue sizes of β-tricalcium phosphate (β-TCP) micro-granules as carriers to assess antibacterial activity and drug-control release behavior of ampicillin (AMP-) and antimycotic (AMC-). Incorporation of antibiotic into the β-TCP micro-granules and it sustain release behavior could be used as alternative solution to reduce the risk of osteomyelitis and bone infections risks. Methods: Three different residue sizes (less than 300 µm, 300 µm and 600 µm) were prepared and coated with antibiotics solution (20 µg/µl of ampicillin and 100X antimycotic solution) by using two methods; dip and stream coating. After 72 h, 1.5 mL of distilled water was added to the treated (β-TCP) micro-granules at two different pH value (5.0 and 7.4). The extracted solution was further analyzed by Kirby Bauer disc diffusion test and spectrophotometer assay. Results: The solution containing AMC-(β-TCP) micro-granules with the size of 300 µm residue produced the largest inhibition zones against Escherichia coli (E. coli). All residue sizes coated with AMP- showed no antibacterial activity against both strains; Staphylococcus aureus (S. aureus) and E.coli. Additionally, the release behavior of AMC-(β-TCP) micro-granules was found not depending on the pH, but on the size of residue. Complete drug release was rapidly observed within 48 h. Conclusion: Based on this findings, it showed AMC-(β-TCP) micro-granules had an antibacterial activity against Gram-negative strain. Specifically, it can reduced the growth rate of E. coli and the rapid release behavior of AMC(β-TCP) micro-granules help in minimizing the risk-infections in early stage of implantation.
ABSTRACT
The purpose of this study was to evaluate newly fabricated tricalcium phosphate(TCP)/chitosan microgranuls as bone substitutes. TCP/chitosan microgranules were fabricated by dropping TCP-chitosan suspension into the NaOH/ethanol solution. The size of microgranules could be controllable via airflow rate. PDGF-BB was loaded into the fabricated granules via freeze-drying methods(300 ng/20 mg). To evaluate cell proliferation, cultured osteoblasts cell lines(MC3T3-E1) was dropped on the BioOss(R), chitosan microgranules, TCP/chitosan microgranules and cultured for 1, 7, 14, and 28 days. Scanning electron microscopic observation was done after 7 days of culture and light microscopic examination was done after 28 days of culture. PDGF-BB release from the microgranules was tested. Rabbit calvarial defects(8 mm in diameter) were formed and chitosan, TCP/chitosan, PDGF-TCP/chitosan microgranules, and BioGran(R) were grafted to test the ability of new bone formation. At SEM view, the size of prepared microgranules was 250-1000 um and TCP powders were observed at the surface of TCP/chitosan microgranules. TCP powders gave roughness to the granules and this might help the attachment of osteoblasts. The pores formed between microgranules might be able to allow new bone ingrowth and vascularization. There were no significant differences in cell number among BioOss(R) and two microgranules at 28 day. Light and scanning electron microscopic examination showed that seeded osteoblastic cells were well attached to TCP/chitosan microgranules and proliferated in a multi-layer. PDGF-BB released from TCP/chitosan microgranules was at therapeutic concentration for at least 1 week. In rabbit calvarial defect models, PDGF-TCP/chitosan microgranules grafted sites showed thicker bone trabeculae pattern and faster bone maturation than others. These results suggested that the TCP/chitosan microgranules showed the potential as bone substitutes.