Three Novel Injectable Calcium Sulphate And Calcium Phosphate Bone Substitutes

Bone is the second most implanted tissue in the body, after blood. Injectable bone substitutes which can be used with minimally invasive surgical techniques overcome the practical disadvantages of blocks or granules. They are easily mixed intraoperatively, moulded to shape and set in vivo to porous HA. They have been extensively investigated in bone defect moldels. Ideally, efficient bone substitutes are resorbed at a rate similar to the rate of bone formation. Thus they are able to provide some structure support and facilitate creeping substitution by the host bone. Synthetic bone grafts usually consist of calcium sulphate and calcium phosphate, or combinations of these minerals. Calcium phosphate is very biocompatible with slow resorption, and calcium sulphate has a resorption rate that is more rapid than the rate of bone ingrowth. The purpose of the study is to develop three novel injectable bone substitutes for bone rapair with better properties compareable to trabecular bone and that encourages new bone to grow in and remode the bone defect.Part ICharacterizations of a novel injectable calcium sulphate /hydroxyapatite bone substituteObjective: To analyze the characterizations of a novel calcium sulphate/ Hydroxyapatite as an injectable bone substitute in vitro and in vivo. Methods: The compound material was obtaind by mixing Calcium Sulphate Hemihydrate(CSH) with 40wt% sintered hydroxyapatite (HA).The setting time, compressive strength and injectable time were measured after mixing the material with Omnipaque. Tissue response, material resorption, bone ingrowth and material strength were studied in the rat and rabbit model. Results: The initial setting time is 16.6±1.3 min; the final setting time is 25.5±2.6min; .The compressive strength is 10.698±0.595MPa; The injectable time is 5.8±0.43 min; Increasing the HA content decreased the compressive strength , setting time and injectable time of all materials. Good tissue response in both rat and rabbit model without inflammatory reactions or fibrous tissue was observed. The trabecular bone surrounded the HA particals once the calcium sulphate was resorbed. The compressive strength of the bone substitute was comparable to that of trabecular bone. Conclusion: Calcium sulphate combined with 40wt% HA fulfils the requirements of injectale time , setting time and compressive strength for clinical use as an injectable bone graft substitute, it could be applicable in larger cancellous bone defects with success.Part IICharacterizations of a novel injectable calcium phosphate/calcium sulphate bone substituteObjective: To analyze the characterizations of a novel injectable calcium phosphate/calcium sulphate as an injectable bone substitute in vitro and in vivo. Methods: The compound material was obtaind by mixing Calcium Sulphate Hemihydrate(CSH) with alpha-tricalcium phosphate (α-TCP). The setting time, compressive strengh and injectability were measured after mixing the material with water. Tissue response, material resorption , bone ingrowth and material strength were studied in the rat and rabbit model. Results: The initial setting time is 15.8.8±0.58 min ; The compressive strength is 23.1±2.3MPa; The injectable time is 4.29±2.3 min; Increasing the CSH content decreased the compressive strength ,setting time and injectable time of all materials. Good tissue response in both rat and rabbit model without inflammatory reactions or fibrous tissue was observed. The osteoconductive matrix provide the strength of the material and ensures guidance for reparative bone tissue as the CSH crystals resorb. Conclusion: Calcium phosphate combined with 20wt% CSH fulfils the requirements of injectale time ,setting time and compressive strength for clinical use as an injectable bone graft substitute.As a biphasic α-TCP/CSH bone substitute,calcium sulphate dissolves at a constant rate producing porosity,both at the surface and in the material bulk.The constant dissolution rat may make the material suitable for creeping substitution by the host bone anf use as a drug delivery system.Part IIIObjective: To observe biocompatibility and osteointegration of the silicon-doped calcium phosphate cement in vivo. Methods: Bone harvest chambers were implanted bilaterally in the proximal tibial of six mature rabbits. The bone harvest chamber has a transverse 1mm wide pore, providing a continuous canal through the chamber for tissue ingrowth. α-TCP+1wt%silicon was implanted in the experimental group, and only α-TCP(alpha-tricalcium phosphate) was implanted in the control group. The tissue harvested from the chambers at 1, 2 ,3 weeks after implantation were evaluated by light microscopy and histomorphometry. The number of osteoclasts, bone formation and the new bone contact to the materials were analyzed in histological specimens with HE , Goldner and TRAP staining. Results: No inflammation was observed during observation period. The number of osteoclasts, the bioactivity of osteoblasts and osteointegration around the materials were increased in the tissue with α-TCP+1wt% silicon compared with α-TCP. Conclusion: Silicon-doped calcium phosphate cement has good biocompatibility and enhanced osteogenic ability.