The Construction Of A High Strength Bone Repair Mesoporous Silica Composite Scaffold And Research Of Its Microspheres’ Drug Release Mechanism

Nowadays, no matter in China or abroad, transplantation of traditional materials such as autograft or allograft bone has fatal flaw in clinical application. Medical profession are more prone to using artificial materials. Among them, the polymer-based materials are in favour widely. Polymer-based materials can be shaped easily, and their performance can be adjusted through different modification methods to meet the clinical needs of bone repair. The biological performance of bone repair materials has a great relationship with their constituent components and something(such as drugs, ions or active factors) which released from them. This topic is aimed at modifying the traditional PLGA scaffolds, by adding bioactive components or by modifying scaffolds’ surface, to improve scaffolds’ biological response characteristics. In addition, we also studied the mechanism of drug(hydrophilic or hydrophobic) released from microspheres. And the related mathematical model was established, which provided the theoretical basis for the preparation of drug carrier with sphere.Considering the biological security and delivery performance, we blending the HMS and PLGA first. On the one hand, HMS is proved to be biological safety by cytotoxicity and animal experiments. One the other hand, HMS with the formation of the honeycomb structure, and has big specific surface area, which has the potential as in vivo drug release carrier. By adding HMS, the compressive strength of PLGA was increased about 16 ~ 44 times, which can meet the requirements of clinical bone repair materials. And solving the embarrassing problem that the strength of polymer based material was insufficient.HMS/PLGA scaffold has excellent physical and chemical properties. However, its biological activity remains to be further enhanced to meet the clinical needs. In this study, we modify the HMS and composite scaffolds in three ways, namely doping trace bioactive elements with HMS, surface biomimetic mineralization and introducing inorganic active material. After modification, the scaffolds’ biological properties were improved significantly.We study the effect that after introducing calcium inorganic active component into HMS/PLGA scaffolds. On the one hand, by in vitro mineralization processing, we get the apatite/HMS/PLGA scaffolds. The cytocompatibility of the scaffolds were enhanced significantly, and the number of BMSCs cultured in scaffolds was increased to about 185%. At the same time, this process have little effect with the compressive strength of HMS/PLGA scaffolds. On the other hand, by introducing nano calcium carbonate into HMS/PLGA scaffolds, the number of cells increased to about 80%. At the same time, the ALP that stem cells secreted also increased to about 30%, and the secretion of collagen were significantly increased. The biological performance of the composite scaffolds were further enhanced.By doping the bioactive lanthanum into HMS, its biological response characteristics was enhanced significantly. By culturing BMSCs with La-HMS, La-HMS release tiny amounts of lanthanum ion to regulate the osteogenesis ability of stem cells, and ALP, Col-I, OCN and RUNX2 secretion of cells are increased by about 35%, the secretion of calcium nodules, collagen were also increased too. It means that doping lanthanum can significantly enhance the biological response characteristics of HMS/PLGA scaffolds.To study the drug release mechanism of HMS/PLGA microspheres used for treatment of bone tuberculosis, hydrophilic drug INH and hydrophobic drug RIF were selected as model drugs. The results show that the release performance of composite microspheres is better than single HMS or PLGA. Making the release cycle extended to more than 60 days, and solving the problem that the release of drugs from pure HMS and PLGA is too fast. Under the assumption that drug is loaded into the HMS, and drugs-loaded HMS were scattered in the microspheres uniformly, we established a drug release mathematical model on the basis of drug distribution status. The model has good applicability for the release of two drugs. And data fitting correlation are all above 0.96. This model can be used to further guide the preparation of drug scaffolds.