| When bone defects exceed critical dimensions,bone tissue cannot achieve self-repair and healing.Artificial bone transplantation can be prepared based on the volume and shape of bone defects,providing the corresponding form and structure support at the defect site,ultimately achieving large-area bone defects repair.Bone scafford is crucial for artificial bone grafting.PLLA is a biocompatible polymer material approved by U.S.Food and Drug Administration for clinical use,but its drawbacks such as difficult to prepare porous structures,poor mechanical performance,and lack of biological activity limit its application.This doctoral dissertation proposes that use nanoparticles（nano-Fe3O4 and nano-hydroxyapatite）as the toughening and strengthening second phase,use in-situ generation methods to enhance the interfacial adhesion between composite materials to improve the biological activity of scaffolds,and use laser additive manufacturing technology to accurately prepare the L-polylactic acid composite artificial bone scaffold,which integrates three-dimensional porous porous structure,proper mechanical properties and excellent biological activity.Finally,the biocompatibility and bone defect repair ability of the composite bone scaffold were evaluated from in vitro cell experiments and in vivo animal experiments.The main research content and innovation points are as follows:（1）Aiming at the difficulty of controlled preparing the porous structure of L-polylactic acid bone scaffolds,it is proposed to use selective laser sintering additive manufacturing technology to additively prepare L-polylactic acid bone scaffolds with three-dimensional personalized shape and internal interconnection porous structure.The key process parameters for the quality of laser selective sintering of polymer bone scaffolds were determined through pre sintering experiments of L-lactic acid bone scaffolds.The powder heat transfer and sintering mechanism in the laser sintering process were found out.The laser manufacturing process was optimized through orthogonal experimental design,and the influence law of multi-parameter coupling such as laser power,scanning speed,and scanning spacing on the molding performance of L-polylactic acid bone scaffold was revealed,and adjustable and controlled preparation of three-dimensional porous structures of bone scaffold was achieved.（2）Aiming at the problem of low mechanical properties of L-polylactic acid bone scaffolds,it is proposed to use Fe3O4 nanoparticles with high strength and high modulus as inorganic dispersed phases to enhance the mechanical properties of L-polylactic acid bone scaffolds.The dispersion properties of magnetic nanoparticles with different composite component addition ratios in polymer matrix scaffolds were clarified,and the influence of particle filling on the microstructure and mechanical properties of L-lactic acid bone scaffolds were clarified,and the toughening and strengthening mechanism of Fe3O4 nanoparticles on L-polylactic acid based bone scaffolds was revealed,which includes:uniformly dispersed rigid nanoparticles filling and particle extraction pore effect,increasing specific surface area and densifying through sintering to enhance interface adhesion and bonding between the matrix and dispersed phases,increasing the probability of entanglement between polymer chains,and improving effective local stress transfer.Ultimately,the compressive strength and modulus of the L-lactic acid bone scaffold are increased by 63.4%and 78.9%,respectively,while the tensile strength and modulus are increased by 41.9%and 97.1%.（3）Aiming at the problem of lack of biological activity of L-polylactic acid bone scaffolds,it is proposed to use nano hydroxyapatite to give the bioactivity of L-polylactic acid bone scaffold.Considering the problem of weak interfacial adhesion in the composite preparation of bioceramic nano hydroxyapatite and L-polylactide polymer,which leads to insignificant enhancement of activity,a method of bionic in-situ generation of nano hydroxyapatite with polydopamine was proposed to effectively improve the biological activity of L-polylactide bone scaffold.The mechanism of hydroxyapatite crystal nucleation and growth induced by polyamine anchored on the surface of L-polylactic acid particles through strong hydrogen bond,calcium ion enrichment through chelation,and phosphate ion adsorption through electrostatic interaction was mainly revealed.It is clarified that the hydroxyapatite/L-polylactic acid composite bone scaffold prepared by in-situ generated nano hydroxyapatite can induce the formation and mineralization of bone like apatite layer by releasing calcium ion and phosphate ion,endow and enhance the biomineralization ability and alkaline phosphatase activity of the scaffold,which improved the adhesion,proliferation,and differentiation of human bone mesenchymal stem cells on the scaffold,resulting in a 20.8%increase in cell proliferation rate on the 7th day.At the same time,the stress transfer efficiency from the L-polylactic acid matrix to the nano hydroxyapatite reinforcement phase was improved by strengthening the interface bonding,and the compressive strength and tensile strength of the composite bone scaffold were increased by 202.1%and 191.6%,respectively.（4）Aiming at the problem of lack of biological evaluation of hydroxyapatite/L-polylactic acid composite artificial bone with excellent mechanical properties and biological activity,an animal experimental model of bone defect with critical size of rabbit radius was constructed to conduct experiments to evaluate its biocompatibility and bone defect repair ability.At the same time,the in vivo study and verification of the in situ growth of nano hydroxyapatite on the improvement of scaffold cell activity were carried out,and the bone formation ability was checked in the large bone defect model in vivo through observation,computer tomography analysis,histological evaluation,etc.The experimental results showed that the hydroxyapatite/L-polylactide composite bone scaffold played a good mechanical support role after being transplanted into the rabbit radial bone defect,and had good biocompatibility and biodegradability in vivo without obvious toxic effects.The composite bone scafford also showed excellent biological activity,promoted the formation of new bone tissue and the repair of bone defects in vivo,and improved the ability of bone bonding and bone conduction.Compared with the pure L-polylactic acid scaffold,the bone volume/tissue volume and bone mineral density increased by 44.44%and 41.73%,respectively.Pictures:58,Tables:14,References:196... |
