Study Of Programmable Chitosan Biomimetic Bone Grafts And Its Drug Release Behaviors

Bone necrosis, bone tuberculosis, osteoporosis and bone tumors lead to large-sizedbone defects. In China, the population of patients suffering the bone defects is morethan three million annually. In recent years, the research of biomimetic bone grafts ismostly focused on composition. The research related with bone grafts with biomimeticnature bone structure is seldom, because the natural bone has a complex andhierarchical structure which is difficult to build by engineering method. Therefore, it isin urgent to study the biomimetic bone graft with similar structure and composition withnatural bone.Based on functional concentration wave, chitosan hydrogel with a circumferentiallamella structure was designed and built programmablely. The multi-layered structure ofhydrogel was characterized using optical microscope. Meanwhile the stratificationmechanism, as well as the regulate and control rule of wave mode on layer number,layer thickness and layer configuration were analyzed. To increase the range ofregulation and design finesse, sodium dihydrogen phosphate was introduced to thereaction system. Using SEM and ESEM, the structure of hydrogel was characterized toexplore the effect of weak acid treatment on chitosan hydrogel. The regulation effect oflayered chitosan template to in-situ synthesized mineral was also studied with the helpof XRD. Additionally, based on microsphere assembly, combining with liquid nitrogentreatment process of microspheres, the chitosan/hydroxyapatite composite mimickingthe structure and composition of cancellous bone was prepared. The in vitro releasebehavior of tuberculosis drug RFP and DSP from biomimetic chitosan scaffolds wasinvestigated.The results show that the layer thickness is proportional to time length under thecondition of a fixed NaOH concentration. At the same time, the thickness is notinfluenced by amplitude, but by the variation of amplitude. More specifically, theincreasing amplitude leads to thinner layers, and vice versa. By adjusting the amplitudeand immersion time of the concentration wave, concentric layered chitosan hydrogelwith characterized thickness arrangement belonging to3D Liesegang rings structure canbe obtained which can be explained by reaction-diffusion theory. What's more, Thedesignable minimum thickness reached20?m. Sodium dihydrogen phosphate has apotential to support more sophisticated design of circumferential lamella structure.After high-temperature sintering, the chitosan/apatite composite microspheres withdifferent apatite content (30%,50%,70%) modeled by nitrogen process exhibitinterconnected porous structure which is necessary for cancellous bone. Using aceticacid solution (1vol%) as binder, dried chitosan/apatite composite microspheres were assembled into a tube. Filled with sintered apatite ceramic microspheres in a closelypacked way, the cancellous bone scaffold with high porosity was eventually obtained.Moreover, the scaffold can be designed with a random s apatite e and apatite content.After mechanical detaching and drugs loading layer by layer, the "over closely"assembled scaffold with mimicked circumferential lamella structure achieves along-term drug release. In the effective concentration range, RFP was released to60days in vitro continuously, and the layered structure makes fast-soluble drug (RFP)release generate volatile fluctuations in the early40days. On the contrary, the layeredstructure had no significant effect on release characteristic of water-soluble drug.