Preparation Of PLGA/HMS/β-TCP Microspheres Scaffolds And Research On Drug Release

With the continuous development of science and technology as well as the increasing incidence of certain emergencies, contributing to the possibility of accidental injury of human bone increased. Also bone tuberculosis account for 3-5%, therefore the need for new type of bone repair material is also increasing. Poly(lactic-co-glycolic acid)(PLGA) is one biodegradable polymer which has good biocompatibility, and the final degradation products are water and carbon dioxide, so it does not produce irritating or toxic substances to the body tissues. As a kind of novel mesoporous silicon material, Hexagonal mesoporous silica(HMS) has the channels with long-range order structure, high porosity, specific surface area and a large number of silanol bonds on the surface, hence HMS has good adsorption ability for some drugs. The rate of Ca and P ions is 1.5:1 in β-tricalcium phosphate(β-TCP), and Ca and P ions can be used to form the new bone tissue directly, presenting β-TCP with good biocompatibility. Based on the properties of PLGA, HMS and β-TCP, this experiment is to prepare composite microspheres, scaffolds and drug loading microspheres, then testing the relative functions on bone tissue repairing.The first part of this experiment is the preparation of PLGA/HMS/β-TCP composite microspheres. the amounts of HMS and PLGA are determined by reading the relevant papers, PLGA/HMS/β-TCP composite microspheres are prepared by emulsion solvent evaporation method through adding different amount of β-TCP in the PLGA and HMS. With testing the contact angle, thermal analysis, SEM and XPS for PLGA/HMS/β-TCP composite microspheres, we find that the contact angle will increase as the growing amount of β-TCP, also the surface of the composite microspheres will be much rougher which is good for cell proliferation and differentiation. Compared with the PLGA microspheres and PLGA/HMS microspheres, the thermal stability of microspheres is increased by the introduction of β-TCP.The second part is preparing scaffolds. In this experiment, PLGA, PLGA/HMS and PLGA/HMS/β-TCP scaffolds are prepared by sintering method at 60℃, 65℃ and 70℃, and the sintering time is 1h. The PLGA/HMS/β-TCP-0.3 microspheres were prepared at 90℃ with 2h, 3h and 4h, respectively. Through the SEM analysis for microspheres under different temperatures. After adding HMS and β-TCP, the adhesion degree between the microspheres will decrease gradually. With increasing temperatures, the degree of adhesion between the microspheres also increase in the same materials. The porosity of the scaffold is also related to the materials and the sintering temperatures. The introduction of inorganic powders can hinder the bonding between the particles, and then increase the porosities of the scaffolds. However, high temperature will strengthen the degree of bonding between the microspheres, thus reducing the porosities of the scaffolds. Through testing mechanical strength of the microspheres under different temperatures, HMS can significantly improve the compressive strength and the compressive modulus of the scaffolds, and the compressive strength and the compressive modulus will continue to increase after adding β-TCP. Analyzing the degradation curves of scaffolds, PLGA/HMS scaffolds have the fastest speed, and the rate will be slower after adding β-TCP.The third part is the preparing drug loaded microspheres. At first, rifampicin(RIF) is combined with HMS in advance, then make the drug loaded microspheres through compositing HMS-RIF with PLGA and β-TCP. By comparing the release of HMS-RIF and β-TCP-RIF, it is clear to see that HMS has better drug-loaden ability. In this research, we test the influence of the amount of β-TCP and CH2Cl2 on the release profiles. The results show that the less number of CH2Cl2 lead to the smaller the particle size and lower encapsulation efficiency. While β-TCP does not affect the release curves significantly.The fourth part is cell experiment. the cell numbers are observed on 1st, 4th and 7th days, showing all scaffolds have good cytocompatibility. The PLGA/HMS/β-TCP-0.3 scaffolds have the largest numbers of cells at the same time. The reason is that the increase of the roughness of the microspheres can provide the cell attachment sites, also Si, P and Ca ions can help the growth of cells on the scaffolds.