The Preparation Of, And Experimental Study On Compound Bioactive Artificial Bone(CBAB)

The Preparation of, and Experimental Study on Compound Bioactive Artificial Bone CCBAB)ABSTRACTCalcium Phosphate Cements (CPC), or named Hydroxyapatite Cements (HAC), was a novel and superior biomaterial for bone repair. The superiority lay in that CPC had some unique properties which common materials such as PMMA didn't have as well as all properties necessary for implanted materials. These unique properties included bioresorbability, excellent biocompatibility, slight exothermic reaction, tight interface, sustained releasing of drug and being able to be molded at will. However, CPC biodegraded and colonized by new bone too slowly, and this intrinsic drawback limited severely its clinical application. Bone Morphogenetics Proteins (BMP) was a cytokine which had definite osteoinductive activity and able to accelerate the regeneration and repair of bone. But an ideal carrier or delivery system was absolutely necessary otherwise BMP could not exert its osteoinductive activity. The ideal carrier for BMP had been sought for decades but no satisfactory one had been found. In view of the excellent properties and intrinsic drawback of CPC and BMP and the coincident complementarity between CPC and BMP, we planed to compound recombinant human BMP-2(rhBMP-2) with CPC to a novel bioactive material. Because loading too much rhBMP-2 in CPC might decrease the biomechanical index inevitably while too little rhBMP-2 might result in low bioactivity, two designs of the CPC/rhBMP-2 compound were drawn. One design was to keep the biomechanical properties mainly and to be used for bone filling, so relatively less rhBMP-2 be loaded in compound. The other was to possess enough bioactivity of rhBMP-2 and the biomechanical indexcould be neglected to some extent if necessary, so much more rhBMP-2 be loaded and this material mainly be used to treat nonunion of fractures and accelerate bone healing. The goal of this research was to develop the first designed material and the following five experiments had been undertaken:1. Study on the affection of loading BMP on CPC's solidification and properties. In order to study the affection of loading BMP in CPC on the CPC's solidification and the compound's properties, we compounded CPC with recombinant human bone morphogenetic protein-2 (rhBMP-2) in the ratio of 1 g CPC powder to 1, 3, 5, 10 mg rhBMP-2 respectively. Such indexes as solidifying time, maximum breaking strength, maximum compressive strength, XRD figure, IR spectrum and SEM image were got with macroscopy, biomechanics testing instrument, XRD, IR and SEM. Results showed that there was no significant difference among experimental groups and control group in solidifying time, maximum breaking strength, maximum compressive strength, XRD figure, IR spectrum and SEM image (f>0.05). It can be concluded that compounding CPC powder with rhBMP-2 in the ratio of 1 g CPC powder to 1 mg~10 mg rhBMP-2 has no remarkable affection on the solidifying rate, the biomechanics strength and the cellular structure of the CPC/rhBMP-2 compound. The ratio of 1 g CPC powder to 5 mg rhBMP-2 is optimal. The novel biomaterial, which we were to compound in this optimal ratio, was named Compound Bioactive Artificial Bone (CBAB).2. In vitro study of CPC's sustained release of BMP. In order to study CPC's sustained release of rhBMP-2 and its kinetics in vitro, we immerged the CPC/rhBMP-2 compound (1 g CPC powder to 5 mg rhBMP-2) into 0.01 mol/L phosphate buffer solution. The solution including rhBMP-2 released from CPC/rhBMP-2 compound was extracted after 1, 2, 3, 4, 7, 14, 30, 90, 180 and 360 days respectively. The extracted solution was analyzed by Liquid Chromatograph. The release profile of rhBMP-2 from CPC was scaled and its kinetics was assayed. Results showed that rhBMP-2 had been released rapidlyduring the 1st to 7th day, slowly and lastingly during the 14th to 360th day, and almost at a platform period during the 7th to 14th day. The release of rhBMP-2 from CPC/rhBMP-2 compound during the 14th to 360th days followed the Higuchi m...