Bisphosphate Modified Calcium-targeted Nanoparticles And Their Application In Bone Tissue Repair

Calcium phosphate materials are widely used for bone tissue regeneration and repair.In the process of clinical application,calcium phosphate material implants usually fail due to bacterial infection,and in addition,calcium phosphate materials lack the ability to induce osteogenic differentiation of stem cells,which makes it difficult to fully meet the requirements of bone repair.The necessary surface modification of calcium phosphate materials is the key to solve the above problems.However,calcium phosphate materials are chemically stable,and surface modification by functional group grafting and chemical bonding is usually difficult.To address this challenge,this thesis proposes to modify the drug-loaded nanoparticles with calcium-targeting ability by using bisphosphonic acid groups to target and bind to calcium phosphate materials and release drugs,thus providing a simple and easy means for surface modification of calcium phosphate materials.1)The construction of calcium-targeting nanoparticles and the study of their targeting performanceIn this thesis,we designed and constructed nanoparticles with calcium targeting function,i.e.poly(lactic-co-glycolic acid)(PLGA)nanoparticles with polydopamine coating modified by bisphosphate.The calcium-targeting ability of the nanoparticles was examined by in vitro experiments.The results showed that these nanoparticles can efficiently target calciumcontaining materials,have a high binding rate to hydroxyapatite,and exhibits good cytocompatibility.Therefore,this calcium-targeting nanoparticle can be loaded with drugs and used for surface modification of calcium phosphate materials.2)The construction of the antimicrobial functionalized surface of calcium phosphate material based on calcium-targeted nanoparticlesTo address the problem of infection in bone implants,calcium-targeted nanoparticles loaded with antibiotics(triclosan)were used to modify hydroxyapatite to construct an antimicrobial functionalized surface.The in vitro slow-release ability of the nanoparticles to triclosan was evaluated by in vitro slow-release experiments,and the in vitro antimicrobial performance of the hydroxyapatite slow-release system loaded with triclosan nanoparticles was evaluated using S.aureus and E.coli,respectively.The hydroxyapatite slow-release system loaded with triclosan nanoparticles could release triclosan slowly for more than one week,and could kill more than 99% of S.aureus and E.coli,exhibiting efficient broad-spectrum antibacterial function.3)The construction of the functionalized surfaces for osteogenic differentiation of stem cells of calcium phosphate material based on calcium-targeted nanoparticlesIn order to endow the material with the ability to promote osteogenic differentiation and further meet the demand of bone repair,calcium-targeted nanoparticles loaded with dexamethasone were used to modify the hydroxyapatite material and construct a functionalized surface to promote osteogenic differentiation of stem cells.The slow-release performance of nanoparticles on dexamethasone was evaluated by in vitro slow-release experiments,and the cytocompatibility and the ability to promote osteogenic differentiation of stem cells in vitro of the hydroxyapatite slow-release system loaded with dexamethasone-containing nanoparticles was evaluated by adipose mesenchymal stem cells.The results showed that the nanoparticles could be efficiently targeted to the surface of hydroxyapatite to release dexamethasone slowly and promote the proliferation and osteogenic differentiation of stem cells in vitro.Based on the high calcium-targeting property of bisphosphonates,this thesis designed and constructed highly biocompatible calcium-targeting nanoparticles that could be loaded with drugs.The nanoparticles can actively dovetail to the surface of calcium phosphate material by targeting and release drugs slowly,imparting properties of killing bacteria and promoting osteogenic differentiation of stem cells to the implant material.This modification method has the advantages of simplicity,rapidity,and high binding capacity,which solves the shortage of existing means of calcium phosphate material modification and provides a universal method for surface modification of calcium phosphate materials.