The Development Of Surgical Grade α-hemihydrate Calcium Sulfate And Its Related Research

AbstractThe demand of bone grafts for bone defects promotes the development of synthetic bone materials. Among many inorganic bone substitutes, a-calcium sulfate hemihydrate was appreciated by many investigaters on account of its degradation with nearer new bone ingrowth speed, excellent biocompatibility, bone conduction. How to combinie a-calcium sulfate hemihydrate with autogenous bone for restoration of big bone defect, to combine it with antibiotics for bone infections, and to carry all kinds of biological agents had been concerned recently. But it beginned not for a long time. But all surgical grade calcium sulfate materials were imported completely overseas and their prices were very high presently. So in 2004,9, we started to collaborate with Materials and Engineering Institute of Shenyang Architecture College, preparing for Surgical grade a-calcium sulfate hemihydrate.PurposeTo find out a proper formula for the Surgical grade a-hemihydrate calcium sulfate and investigate its physico-chemical property and biocompatibility.Materials and methods(1)Preparation methods: Using method of multi-factor and multi-level factorial design, we evaluated the compressive strength, ratio of gypsum to water and interval porosity, to find out an ideal formula of a- hemihydrate calcium sulfate. (2)Physico-chemical property: Study in-vitro resorption, PH, Ca²⁺, compressive strength, temperature, X-ray disffraction and surface characteristic of CCaS. (3)In-vitro biocompatibility: According to ISO 10993-5 and GB/T 16886-1 standards, we performed haemolysis tests, cytotoxicity test by MTT methods, cell adherence to materials, pyrogenic tests, allergic tests, and implants into muscle. (4)Osteogenous experiments: We implanted CCaS cylinders and Osteoset^? pellets into bone defect in the distal femur of rabbits. Using general observations, X-ray, bone density measurements, histological observation, immunofluorescence labeling and mechanical experiments, we investigated in-vivo degradation property of two kinds of synthetic bone and the effects of them on bone ingrowths of bone defects.Results(1) Preparation methods: Citrated hemi-hydrate calcium sulfate (CCaS), which was made using vapor-heat methods, complicateted salt solutions, high temperature and pressure for 6 hours, had more ratio of gypsum to water, less internal porosity and higher compressive strength. (2) Physio-chemical property: CCaS had uniform crystalline structure, high compressive strength, and a relatively slow resorption speed compared with Osteosef pellets. It could make environments of higher calcium around synthetic bone, but does not change local PH. It could in situ harden and produce less heats. 20 minutes after setting, compressive strength of CCaS can exceed that of cancellous bone. (3) Biocompatibility: The rate of haemolysis was 0.34 percent. Materials had no toxicity to mesenchymal cell proliferaions. Mesenchymal cells could adherece to and proliferate on the surface of materials. The body temperature had no significant changes in pyrogenic test. No erythema, papule and nodule happened in the test of intradermal injection. 6 weeks after implanted into muscles, it was absorbed completely. Throughout its absorbtion, fiber cyst around synthetic bone formed. Inflammatory response and foreign body response was not observed in surrounding tissues. Therefore, CCaS corresponded to the demands of medical biomaterials.(4) Osteogenous experiments: CCaS and Osteoset? restored bone defects completely. Inflammatory and foreign body response were not observed. There were no difference in bone density, compressive strength, osteogenous quantification between two synthetic bones. But degradation speed of CCaS was slightly slower than that of Osteoser9.Conclusion1. An ideal formula for a-hemihydrate calcium sulfate has been achieved. We call it CCaS.2. CCaS is very appropriate for restoration of non-structured confined bone defect, and carrier of antibiotics and biological factor.3. Proved by in-vitro and in-vivo tests that CCaS has a good biocompatibility.4. Proved by osteogenous study that both CCaS and Osteoset9 are ideal synthetic bones. However resorption speed of CCaS is less slowly than Osteoset*.