| The fracture of bones due to various traumas or natural aging is a typical type of a tissue failure.An operative treatment frequently requires implantation of a temporary or a permanent prosthesis,which still is a challenge for orthopedic surgeons,especially in the cases of large bone defects.A fast aging of the population and serious drawbacks of natural bone grafts make the situation even worse;therefore,there is a high clinical demand for bone substitutes.However,any type of biologically derived transplants appear to be imperfect solutions,mainly due to a restricted quantity of donor tissues,donor site morbidity,as well as potential risks of an immunological incompatibility and disease transfer.In this light,manmade materials(alloplastic or synthetic bone grafts)stand out as a reasonable option because they are easily available,might be processed and modified to suit the specific needs of a given application.What is more,there are no concerns about potential infections,immunological incompatibility,sterility and donor site morbidity.Investigations on artificial materials for bone tissue repair appear to be one of the key subjects in the field of biomaterials research for clinical applications.Therefore,it is one of the essential research projects to prepare bone substitutes which have the similar biocompatibility and mechanical property as natural bone to accelerate bone regeneration.The process of bone regeneration is composed of a series of elaborately organized biological induced and transmitted events,which involve many types of cells and intracellular and extracellular molecule signals,and are in specific sequence of time and space to optimize and restore the function of bone.Recently,the mechanism of bone biomineralization has been extensively developed,but the intracellular and extracellular molecule signals in bone biomineralization process induced by man-made calcium phosphates are still unknown.As to the existing status,results in this dissertation are shown as follows:1.The optimized preparation of ultralong hydroxyapatite nanowires(HANWs)and HANWs/sodium alginate(SA)hybrid hydrogelsHydrogels with 3-dimentional cross-linked structures are widely used in various biomedical fields such as bone repair scaffolds,drug carriers and biosensors.However,the applications of hydrogels are greatly restricted because of their poor mechanical properties.Currently,nanocomposites,double network systems,hydrophobic association,macromolecules,and nanoparticles are mostly adopted as cross-linking agents to enhance mechanical properties of hydrogels.In this study,ultralong hydroxyapatite nanowires with lengths of larger than 100 ?mup to nearly 1000 ?m are prepared and used to enhance the mechanical properties of sodium alginate(SA)-based hydrogels.Using divalent calcium ions as the cross-linking agent,the hybrid HANWs/SA hydrogels containing various percentages of HANWs are obtained.The as-prepared HANWs/SA hybrid hydrogels have a porous structure with pore sizes ranging from about 200 to 500 ?m,which is favorable for the new bone and blood vessels to grow in.The mechanical properties of SA hydrogels can be significantly improved by incorporating HANWs.The tensile Young's modulus of the hybrid hydrogel(HANWs/SA = 2:1)can reach 0.994 MPa which is about 613% that of the pure SA hydrogel.In addition,the maximum compressive modulus(E50%)is as high as 0.126 MPa,which is about 163% that ofthe pure SA hydrogel.Due to the enhanced mechanical properties and high biocompatibility,the as-prepared HANWs/SA hybrid hydrogels have promising applications in various biomedical fields such as bone repair.2.Tracking the interactions between calcium phosphate(CaP)nanocarriers and drug molecules using synchrotron technology.It's expected that the drug carrier system can release drug molecules against cancer at first,and then the drug carriers will slowly degrade and induce bone regeneration in the treatment of bone cancer.Obviously,calcium phosphate drug nanocarrier system isan ideal candidate.However,the interactions between calcium phosphate nanocarriers and drug molecules still remain unknown,then it is very necessary to explore/realize/understand their interactions using synchrotron technology to regulate drug loading and release.X-ray near edge absorption spectra show that doxorubicin hydrochloride(Dox)or hemoglobin(Hb)molecules loaded in the CaP nanocarriers have no strong chemical interaction with CaP drug nanocarriers synthezised by microwave-assisted method(including Eu,Nd doped CaP nanocarrier).They are physically adsorbed on the surface of CaP nanocarrier.Some typical structure,such as Fe(II)of Hb molecules,will share electron with amino-group of CaP nanocarriers.Therefore,the loading capacity and release property of the CaP nanocarrier drug can be regulated by surface modification.3.Enzymatic reaction generated biomimic calcium phosphate mineralsMitochondrial mineral plays a critical role in initiating extracellular mineralization.However,the function mechanisms of the mitochondrial mineral are still a mystery.Herein,we report an in vitro enzymatic reaction strategy for the generation of biomimic amorphous calcium phosphate(EACP)nanominerals by an alkaline phosphatase(ALP)-catalyzed hydrolysis of adenosine triphosphate(ATP)in a weakly alkalescent aqueous condition(pH 8.0~8.5),which is partially similar to the mitochondrial environment.Significantly,the EACP nanomineral obviously promotes the autophagy and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by activating an AMPK related pathway,and displays a high performance in promoting bone regeneration.These results provide an in vitro evidence for the effect of ATP on the formation and stabilization of the mineral in the mineralization process,demonstrating a potential strategy for the preparation of the biomimic mineral for treating bone related diseases. |
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