Research On Biomimetic Synthesis And Property Of Drug Carrier Of CPP/CS Composite For Bone Repair And Therapy

The research object of this paper is to synthesize the good CPP/CS complex TCSCC drug carrier for bone repair and therapy by biomimetic synthesis, and research on the compound method, synthesis condition, structure characteristic, mechanics property, biodegradable drug delivery-controlled property, effect of resisting golden staphylococcus and biocompatibility of osteoblast etc..CPP (Calcium Polyphosphate) possesses excellent biocompatibility, bioactivity, osteoinduction and biodegradation. There are two defects when the single CPP is applied to the material of the bone repair. One is that CPP degrades too slow, another is that CPP loses the strength too quick meantime. For resolving these defects, CS (Chitosan) nature polymer is elected to be organic component for its excellent biocompatibility, biodegradation and good toughness. Suspension heat-dispersion complex method is applied by biomimetic synthesis method to make CPP inorganic component and CS organic one form the CPP/CS bone repair composite material which owns good property of mechanics and degradation-controlled. The pore diameter and porosity of clubbed material were detected and its mechanism of forming pore and compound was explored in this paper. The CPP/CS beads composite material were synthesized by the same compound method for bone repair, and theirs property was compared with the clubbed material one.The chronic osteomyelitis is used to occur in the process of repair and therapy of fracture, bone absence and bone defect, which is mainly caused by the golden staphylococcus. For the purpose of bone repair and therapy of chronic osteomyelitis, the TH (Tetracycline Hydrochloride) is elected to restrain and kill the the golden staphylococcus. TCM (TH-CS Microsphere) is synthesized by the compound crosslink inverse-emulsion polymerization; STCM (compound drug-carried microsphere) is prepared by the method of the phase separation; TCSCC is made by enclosing STCM into the CPP/CS composite material for bone repair. It has been researched TCSCC structure, synthesis condition, biodegradation, the property of drug delivery, biocompatibility to osteoblast and the property of TH killing the golden staphylococcus. These properties of the composite material are basis of bone repair, therapy of chronic osteomyelitis.Main research results as follows:(1) An especial suspension dispersion method is applied in this experiment through electing, comparing, and searching some synthesis methods, which is called the suspension heat-dispersion compound method. In this method, CPP is suspended in the absolute alcohol at first, and then this solution is dispersed into the heat CS-HAc solution. They can form a homogeneous compound suspension solution. The method is a creative method of compound in this paper.(2) This paper simulates the ingredient, ratio, structure and function of human bone. That takes the CPP and CS into inorganic and organic phase respectively by simulating the human bone component. The 70/30 ratio of CPP/CS is the nearest the ratio of inorganic to organic ingredient in human bone; the -O-P-O- bond in CPP molecule is similar to the high-octane phosphatic bond in ATP (Adenosine Triphosphate), which can deliver energy which is used by osteoblast and promote its growth when the bond is hydrolyzed. So CPP is a biomimetic material of structure and function. CPP/CS club-shaped material (pored by reagent) can be prepared by the suspension heat-dispersion compound method. This composite material possesses the property homogeneous, dense, and strong structure. Its microspheres (using the phase separation method to form pore, not using reagent) can be made too.(3) At first the TCM is synthesized in this experiment which carries the TH drug by applying compound crosslink inverse-emulsion polymerization; secondly TCM is enclosed in SA (Sodium Alginate) to make out compound beads STCM (compound drug-carried microsphere) by using phrase separation method; at last TCSCC which encloses the STCM beads drug-carried can be synthesized by using the material of CPP and CS, which the biomimetic component ratio of CPP to CS is 70 to 30, and the compound material can be formed by suspension heat-dispersion compound method.(4) Research on the CPP/CS composite structure, and explore the mechanism of CPP/CS compound material from molecule structure level. (1) H-bonds formation: oxygen in phosphorous double bond in CPP and amino, hydroxyl in CS can form H-bonds (P=O...H-N-; P=O...H-O-), which makes molecules of CPP and CS create static electricity function. (2) Forming of complex: s, p, d space orbit in calcium ion can accept the electron from isolated electron from N or O element, so they can form complex. The chemical bonds can be produced between CPP and CS in order to make them combine very densely.(5) Research on mechanics property of different component of CPP/CS. The porous composite material has more excellent mechanics property when ratio of CPP (inorganic phase) to CS (organic phase) is 75 to 25, 70 to 30, 65 to 35 respectively. There is the most excellent press strength when the ratio of CPP to CS is 70 to 30 in the composite material, and CPP inorganic phase and CS organic phase are similar to the ingredient of human bone. Therefore, simulation of ingredient and component of human bone can make the most excellent property.(6) Research on biodegradation property of CPP/CS composite material. The composite material has the fastest degradation rate when it is made by 420000 molecule weight of CS, 75.56% deacetylation degree of CS, CPP grain diameter blow 50μm ( sifting through standard screen), and 70/30 ratio of CPP/CS. So the composite material enhances the CPP degradation rate, and it can adjust the degradation rate of composite material to change CPP grain diameter, CS molecule weight and deacetylation degree and ratio of CPP/CS.(7) Research on the property of TCSCC degradation and drug delivery. The process of TCSCC degradation and delivery drug is divided into two stages: small molecule diffused to resolve and drag diffused to deliver belong the first stage (having the phenomenon of delivery arise suddenly). The delivery rule contents the zero order formula P=at+b, which delivery amount "P" is linear to delivery time "t"; that slow degradation of material leads to drug delivery belongs to the second stage. The delivery rule contents the Hignichi formula: P=at^1/2+b, which delivery amount "P" is not linear to delivery time "t". TCSCC has two functions of bone repair and drug delivery. The drug delivery exists from beginning to end the process of material degradation, and simultaneously it repairs bone and cures the chronic osteomyelitis. At the same way, it can adjust the degradation rate of TCSCC to change CPP grain diameter, CS molecular weight and deacetylation degree and ratio of CPP/CS.(8) Research on the material property of the resisting bacteria. The samples of CPP, SA and distilled water do not have the property of resisting bacteria, but the others compound samples have the effect of resisting bacteria except the blank one. TH drug has the most excellent effect to resist the golden staphylococcus. The other composite materials TCM STCM TCSCC carrying the TH drag also have the good property of resisting bacteria.(9) Research on the material biocompatibility to osteoblast. All used raw material and TCM STCM TCSCC synthesis composite material in this experiment do not have toxin to osteoblast, except TH having some harm to osteoblast. The osteoblast growth in material contents the general law of cell sticking, growing, reproducing and differentiating. Innovation points in the paper:(1) The suspension heat-dispersion compound method is one of innovation points, which in this method CPP is suspended in the absolute alcohol at first, and then this solution is dispersed into the heat CS-HAc solution. They can form a homogeneous compound suspension solution.(2) Biomimetic synthesis method in this paper is to elect the CPP inorganic phase, in which the -O-P-O- bond is similar to the high-octane phosphatic bond in ATP , and CS organic phase, which is one of natural polymers. The 70/30 ratio of CPP/CS is about the ratio of inorganic to organic ingredient in human bone, and the composite material possesses the most excellent mechanics property.(3) CPP/CS compound material of bone repair has double functions. CS is a type of nature polymer which possesses the good biocompatibility and biodegradation and can restrain the many bacteria to grow; CPP also possesses the excellent biocompatibility, bioactivity, osteoconduction and biodegradation which can promote the osteoblast to grow. So the CPP/CS composite material possesses the double functions of resisting bacteria growth and repairing the bone defect.(4) TCSCC has the property of biodegradation-controlled and drug delivery-controlled. The CS degradation rate is faster than the CPP in the compound material. Increasing the. CS ingredient in the compound material can enhance composite degradation rate. On the contrary, increasing the CPP ingredient can reduce the compound material degradation. It can adjust the TCSCC rate of degradation and drug delivery by changing CPP grain diameter, CS molecule weight and deacetylation degree and ratio of CPP/CS.(5) TCSCC has multifunctions that TCSCC possesses the functions of resisting the bacteria, bone repair and drug delivery. That is to say when TCSCC repairs the bone simultaneously it delivers the TH drug to kill golden staphylococcus to cure chronic osteomyelitis. So the TCSCC is a type of multifunctional compound material possessing the functions of resisting bacterium, bone repair and drug delivery for bone therapy.