Preparation Of PLLA Dual-drug System Scaffold And Application For GBR In Periodontal Treatment

Periodontitis is a common human oral disease, which lead to the damage in periodontal tissue. GTR(Guided Tissue Regeneration)and GBR(Guided Bone Regeneration)is the best clinic treatments in periodontal diseases until to now. An ideal treatment is to repairing damaged tissue on the premise of control inflammation. In this study, PLLA scaffolds with hierarchical pores were fabricated via a thermal induced separation technique. A controlled-release dual-drug system was prepared while parthenolide and naringin worked as model drugs for antiinflammatory and guiding bone regeneration respectively. The microstructure, mechanical properties, degradation in vitro, drug release properties and biocompatibility were analyzed. The periodontal defects in the second molar of SD rat worked as damage models, while the repair experiment of the models in vivo has been developed based on GBR technique.A PLLA/1,4-dioxane/water ternary system was used to explore the PLLA porous scaffolds.The ratio of solvent/non-solvent, PLLA concentration and coarsening time were used to modulate the microstructure and properties of the sacffolds. In ternary system, increasing the ratio of non-solvent content and PLLA concentration can reduced the porosity of scaffolds,which led to improvement of the compressive strength. However, the effect of the ratio of solvent/non-solvent was larger than PLLA concentration. Extension of coarsening time can also increase the sizes of pores, but there is no more change over one hour. PLLA scaffolds with hierarchical porous presented macropores 150-250 μm and micropores below 10μm were obtained when the solvent/non-solvent of 87/13(1,4-dixone/water) and 5% PLLA concentration were applied, and compressive strength of the scaffold was up to 2 MPa. This hierarchical structure was expected to be an optimal candidate for repairing tissue.Chitosan microspheres(CSM) and Chitosan microspheres loaded with naringin(NIN-CSM)were fabricated by spray drying. The CSM or NIN-CSM had a smooth or serpentine surface with particle sizes about 2-8μm. Dual-drug PLLA scaffold(Parthenolide-PLLA/Naringin-CS Microsphere,PTN-PLLA/NIN-CSM) loaded with parthenolide and NIN-CSM was prepared by the thermal induced separation technique according to the optimal process as before noted. Theaddition of CSM enhanced mechanical properties and hydrophilic, and also promoted the degradation of the scaffold. The degradation products of CSM had a neutralizing effect on the acidic degradation products of PLLA. FTIR results indicated that there may be a hydrogen bonding between PLLA and CSM. SEM showed the CSM uniformly distributed inside the PLLA matrix. A sequential controlled-release of parthenolide and naringin were obtained. The hemolysis rate of 1.86% which indicated the dual-drug PLLA scaffold had good biocompatibility.The cell proliferament was a combined effect of two drugs when co-cultured the scaffold and MC3T3 cells detected by CCK-8. Cells adhered in the micropores and had an ingrowth into the macropores under SEM observation.Degradation experiment in vivo indicated there was no significant inflammatory reaction after implantation and the scaffolds maintained their basic structure for 8 weeks. The degradation of PLLA scaffold could be improved with adding of CSM, but a high CSM content would result in clogging of pores, which affected tissue ingrowth. The periodontal defect repair experiment in vivo showed that the repair area of the dual-drug scaffold groups was up to 50% after implantion for 8 weeks and the continuity of alveolar bone was normal. No obvious bone absorption could be observed. The anti-inflammatory of parthenolide and oestogenic activity of naringin improved the re-construction of the alveolar bone and the repair effect of PTN-PLLA/NIN-CSM dual-drug system was significantly better than non-drug group.The novelty of the study is to prepare a hierarchical porous PLLA scaffold loaded with parthenolide and naringin for GBR. The result provides a new method for the clinical treatment for periodontal disease.