A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2Silicon-substituted calcium phosphate (Si-CaP) was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP) cross-linked networks. In this study, heparin was covalently bonded to the residual -NH 2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2) was bound to conjugated scaffolds by ionic interactions between the negatively charged SO 4 2-clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.
Background: Infected bone is often intractable. An ideal approach is to simultaneously eradicate infection and repair the bone defect. The development of osteoinductive bone graft composites to control antibiotic drug release would be useful for the treatment of intractable bone infections. Objectives: To develop a rat model of osteomyelitis for assessing osteoinductive bone graft scaffolds containing antibiotics and a bone morphogenetic protein.Methods: Si-imprinted calcium phosphate is a new hydroxyapatite derivative used in fabricating bone scaffolds. Vancomycin and bone morphogenetic protein-2 (BMP-2) were loaded onto scaffolds of Si-imprinted calcium phosphate using an established method. The efficiency of the scaffold as a drug carrier system was assessed in vivo. Osteomyelitis was induced in rats by infection of the tibial epiphysis with Staphylococcus aureus (BAA 1680). The success of inducing disease was checked after 4 weeks using bacterial culture and radiography. A 10 mm metaphysis bone was surgically removed and replaced with a drug-loaded scaffold. Histology and X-ray imaging were used to evaluate the implants at 8 weeks post implantation. Results: We successfully established a rat model of osteomyelitis. The causative bacteria were effectively eradicated by vancomycin released from the implants. Enhanced bone formation was observed for the implant samples containing vancomycin and BMP-2 compared with those containing either vancomycin or BMP2 alone.
Conclusions:The newly developed bone scaffold has potential as a vehicle for therapeutic agents to treat bone diseases.
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