Preparation Process Optimization And Surface Modification Treatment Of Porous Poly(L-lactic Acid)(PLLA) Scaffolds

Poly(L-lactic acid)(PLLA)is a material with good biocompatibility and biodegradability,which can be used for bone repair.Porous PLLA scaffolds can be prepared by solvent casting/freeze drying method.This method combines the advantages of porogen technology and freeze drying technology.The PLLA solution was cast into the gaps of the ice particles porogen,and then the solvent and ice particles were removed by freeze drying to obtain a three-dimensional porous PLLA scaffold.The porous PLLA scaffolds prepared by this process have high porosity and good pore connectivity,and no porogen residue remains inside the scaffolds.However,the stability of this preparation process is poor,and the PLLA scaffolds prepared by the method has poor hydrophilicity and low mechanical properties.In this thesis,the optimization of the preparation process of porous PLLA scaffolds was carried out.A new sublimable porogen was prepared and the freeze-thaw properties of the PLLA solutions were also investigated.The formation process of the pore structure of the porous PLLA scaffold,the improvement of the preparation process and the method of surface modification were systematically studied.The preparation method of sublimable microsphere porogen is studied.A mixed solvent having a small surface tension is sprayed into liquid nitrogen to form spherical microparticles.The 1,4-dioxane/water solution was sprayed into liquid nitrogen to form a large number of ice-based microspheres having a size of 300-700?m.The volume ratio of the 1,4-dioxane/water is 70/30.Ice-based microspheres can be used as a porogen which sublimes during lyophilization without residue.The ice-based microspheres are solid,and the macropores of the PLLA scaffolds are formed by sublimation of ice-based microspheres.Two mixed solvent systems(1,4-dioxane/dichloromethane,1,4-dioxane/ trichloromethane)were used to dissolve PLLA to form a series of ternary PLLA solutions.The DSC test results show that the freeze-thaw characteristics of the ternary PLLA solutions are related to the composition and content of the solvent.A solution in which PLLA is dissolved in 1,4-dioxane/dichloromethane(2/1 v/v)is referred to as a DDC-21 solution.The DSC test results show that the DDC-21 solution has only one crystallization peak during the cooling process,and the crystallization peak temperature is-18?;the DDC-21 solution has only one melting peak during the heating process,and the melting peak temperature is 3?.The other ternary PLLA solutions prepared in this paper have two crystallization peaks during the cooling process,and there are two melting peaks during the heating process.The crystallization peak temperature and melting peak temperature of the ternary PLLA solution are related to solvent composition.The effects of freezing and lyophilization processes on the formation of the pore walls of porous PLLA scaffolds were investigated.The PLLA solution was poured into the gaps of the ice-based microspheres to form a pre-scaffold.After the pre-scaffold is frozen and lyophilized,a PLLA scaffold having macroporous,microporous and nanofiber structures can be obtained.The macropores of the porous PLLA scaffolds are spherical,and the size of the macropores is several hundred micrometers.The size of the macropores is approximately the same as the size of the ice-based microspheres.As the size of the macropores increases,the size of the through holes becomes correspondingly larger.The pore walls of the PLLA scaffolds have a special coarse structure,and many micro/nano PLLA fibers can be found on the surface of the pore wall.Micropores are present in the cross section and wall surface of the PLLA scaffolds.The size of the micropores is about several tens of microns.The porous PLLA scaffolds has good pore connectivity.By adjusting the freezing and lyophilization process parameters of the pre-scaffold,PLLA scaffolds with different pore wall morphology can be obtained.The pore wall morphology of the PLLA scaffolds can be divided into three types,which are dense,fibrous and porous.The composition of both the ice-based microspheres and the PLLA solutions can affect the formation of the surface microstructure of the porous PLLA scaffolds.When the freeze-drying temperature is set too high,the solidified PLLA solution will melt.The PLLA solution in the ice-based microsphere gaps will flow in a vacuum freeze-dried environment.The porous PLLA scaffold has a rough surface that facilitates the formation of a coating.The gelatin is first dissolved in an ethanol/water(1/1 v/v)solution to form a gelatin solution,and then the porous scaffolds were immersed in gelatin solution.After centrifugation and lyophilization,a layer of gelatin coating is formed on the surface of the porous PLLA scaffolds.The gelatin coating adheres firmly to the surface of the porous PLLA scaffolds.The gelatin coating is evenly distributed on the surface of the scaffolds,and gelatin does not accumulate inside the scaffolds.The presence of a gelatin coating increases the compressive strength of the scaffolds.Experiments show that both the composite coated scaffolds and the pure PLLA scaffolds have good biological activity.After soaking for a while in the SBF solution,the surface of the composite coated scaffolds and the pure PLLA scaffolds formed a calcium phosphate salt deposit.After soaking for 7 days,the micro/nano PLLA fibers and gelatin coating on the surface of the pore walls were partially degraded.After soaking and degrading in PBS solution for a period of time,the surface of the porous PLLA scaffolds also forms a calcium phosphate salt deposit.After the pure PLLA scaffold was soaked in PBS for 28 days,the viscosity average molecular weight of PLLA was reduced from 410?10 g/ mol to 7.97 ?104 g/ mol.The reduction ratio of the viscosity average molecular weight of PLLA is 20.3%.The mass of the scaffold and the p H of the soaking solution change as the soaking process continues.