Biodegradable Polymer-Coated, Gelatin Hydrogel/Bioceramics Ternary Composites for Antitubercular Drug Delivery and Tissue Regeneration

摘要

A simple and effective strategy for the treatment of osteoarticular tuberculosis is proposed through combining tissue engineering approach with anti-tuberculosis drug therapy. A series of tricalcium phosphate bioceramics (TPB) composites, coated by degradable polymer outside and loaded with rifampicin (RFP)-containing gelatin hydrogel inside, were thus fabricated and successfully applied to deliver antitubercular drug RFP into osseous lesion and concomitantly to induce tissue regeneration. RFP-loaded gelatin hydrogel/TPB composites could be readily prepared by filling RFP-containing gelatin solution into TPB and thenin situcrosslinking of gelatin with calcium ions. Depending on the concentrations of RFP, the loading efficiency of RFP in the composites varied in the range from approximately 2% to 5%. Moreover, the surface of these binary composites could be further coated by a biodegradable polymer, yielding biodegradable polymer-coated, RFP-containing gelatin hydrogel/TPB ternary composites. It was shown thatin vitrorelease of RFP from the ternary composites could be effectively sustained for a long period of time. Besides, these composites revealed good biocompatibility towards the survival of MC-3T3 cellsin vitroand could be used for tissue regenerationin vivoin a rabbit model. The results indicate that TPB ternary composites have great potential for the treatment of osteoarticular tuberculosis.