Modification Of Polypropylene Carbonate And Its Basic Research On Medical Application

Bone defects are often caused by trauma, infection, tumors or congenital diseases, etc. These patients with no remedial treatment would frequently get complications, secondary fractures or osteomyelitis for instance. The serious would loss physical working capacity, even more extremity disability. Nowadays, autologous bone transplantation is the most common method in clinical treatment of bone defect, also get the best effect, but this method easily leads increasing trauma and complication in operation zone of patients, and the source of autologous bone is finite. For solving these issues, researchers in materials and medical profession have been researching and developing new materials to replace autologous bone defect repair materials.There are three main groups of bone defect repair materials which have been researched and applicated in the world: alloy, bioceramics and synthetic biodegradable polymer materials. Although alloy and bioceramics have suitable intensity, they don't have biodegradation. The long-term application of alloy materials in the body may cause the shift of material, so materials often need to be removed by second surgery. Bioceramics are greatly limited to its application because of reasons such as brittleness, being absorbed difficultly, weak bone induction. In recent years, Synthetic biodegradable polymer developed rapidly dues to its characteristics such as biodegradable, biocompatible and plasticity. It has broad prospects in the application of bone defects repairing. The synthetic biodegradable polymer materials of repairing bone defect at home and abroad are these groups, such as PGA, PLA, PGLA and PCL. PLA, PGA, PGLA are the most widely used materials. There are some drawbacks of these materials in their preparations and clinical usings: (1) They are not easily molded because of high temperature of vitrification. (2) Some degradation products are acid products which can cause aseptic inflammation in the body. (3) Material's degradation rate doesn't coordinate with the rate of new bone formation. (4)Compression strength and compression modulus decrease with the porosity's increases, so it is difficulty to achieve standards of human bones. Moreover, the domestic application of PLA products mainly relies on being imported. The high price greatly increases the burden of patients. In short, the existing materials could not satisfy the needs of clinical treatment. It is imperative to research and develop new synthetic biodegradable polymer materials with own independent intellectual property.Polypropylene carbonate (PPC) is an ideal new biomaterials with non-toxic, non-polluting, good transparency, blood compatibility, biodegradable and strong memory with temperature. Because the low hardness of PPC, it is difficult to be made as bone defect repair materials alone. If PPC is modificated on the physical and chemical nature to be closer to human bones, then coupled with its low costs and excellent biocompatibility, it is possible to develop new repairing bone defect using synthetic biodegradable polymer materials which have broad application prospects. Poly-β-hydroxybutyrate (PHB) is a widely spread thermoplastic polyester in the natural world, especially in the bacteria. PHB is a completely biodegradable polymer with good biocompatibility, which initially decomposes toβ-hydroxybutyrate in the body. The final degradation products are CO2 and H2O which would not cause any side effects to human body. When PHB is heated above the melting point, its molecular weight will be reduced to half of the initial value. PHB thermal stability is so poor that it is difficult to mold the material. As PHB has high degree of crystallinity, crystal ball is big and brittle. For the weakness of the narrow range of machinable temperature and poor impact resistance, PHB is restricted in the application, so it could hardly be used as a bone defect repair materials alone.In this study, PPC and PHB were mixed to made a new porous biological material named modified polypropylene carbonate (PM-PPC), which integrate PPC's and PHB's advantages. It is expected that the material will have a good mechanical properties, biosafety, slow degradation and bioavailability in vitro and in vivo. Specific experiments are as follows:Part I: Preparation and parameters measure of new biological materials. PHB and PPC were mixed with the ratio of 70:30 to blend a modified PPC (M-PPC). M-PPC was made porous with salting-out technology. The aperture holes of the porous modified PPC(PM-PPC) were 50～200μm. The porosity was 15%. Mn was 365,000. Mw was 730,000. PDI was 2.0. Compressive strength was 43 MPa. The results showed that the materials were new synthetic porous polymer materials with higher strength which characteristics were similar to human bone's.PartⅡ: The biological safety evaluation for material. Based on "Biological Evaluation method for Medical Devices" relevant standards in ISO 10993 and GB/T 16886, specific tests on PM-PPC's biological safety evaluation were carried on. The tests included: acute toxicity test, pyrogenic test, sensitization test, skin stimulation test, hemolysis test and 52 weeks'implantation test. The experiment results showed that: modified PPC has no acute systemic toxicity, no allergens, no stimulating effect on the skin, good blood compatibility and has no pyrogenic created. The result of alergic reactions was 0 level. Materials hemolytic rate was 1.17%. There was no inflammatory reaction in the 52 weeks of implantation. A complete fiber capsule was emerged in the material implanted zone with no continuing hyperplasia. The results showed that PM-PPC had a good biosafety.Part III: Research of degradation performance. The tests included: composting degradation test, degradation of 52-week trial in vivo and in vitro. Composting degradation test's results showed that the PPC's pH value did not change significantly, and the biological decomposition rate was 75.7 %.The test verificated that PPC was a biodegradable polymer material. The molecular weight and quality of materials were measured in different time points of degradation in vitro and vivo, and the surface was observed by scanning electron microscopy. The results were as follows:In vivo and in vitro, surface cracked and large debris could be seen; 52-week weight loss rate in vitro was 9.87% and 4.45% in vivo, Mn decreased 15.97% in vitro and 10.74% in vivo. Medium's PH value did not change significantly in vitro after 52 weeks. The results showed that PM-PPC degradated in vivo and vitro, with no conspicuous acid and alkaline degradation products formed. Studies have proved that the M-PPC contained the slow degradation character of bone defect repairing material.Part IV: The osteoblasts's compatibility studies. Osteoblasts were the core part which contract with recovering and rebuilding the bone during the bone formation and metabolism procession. In this experiment, SD neonatal rat's cranium osteoblast cells were isolated and cultured through tissue pieces culturing method. Alizarin red staining and staining calcium nodules were used to identificate the three-generation osteoblasts. Using these cells as seed cells cultured with the density of 3.5×105 cells. The growing ability was observed through regularity observation of material-cell's directly contact. The osteoblast cell's vitro compatibility was tested through the material surface cell counting method and scanning electron microscope method. The results showed that osteoblasts could adhere to the M-PPC's surface, extend and proliferate. PM-PPC has good compatibility with bone cell and some content of bone conduction. The material has a certain bioavailability in vitro as bone defect repairing material.PartⅤ:Research of the repiring on rabbit's radius research of M-PPC. Using surgery to cause 2 cm long bone defect on rabbit's radius shaft, remove the periosteum together to establish a rabbit radius bone defect model. General observation, imaging, histological and other means were used to evaluate the repairing bone defects at 2, 4, 8, 12 weeks. PM-PPC repairing results after 12 weeks were as follows: Bone and material were closely combined to form an integer. Imaging showed that os integumentale's sucession was good and the material synostosised with the host bone. Histological test showed that large amounts of trabecular bone could be seen in defect zone with new bone formation. The results showed that PM-PPC with bone conduction and bone formation performance had vivo bioavailability required by defect repairing materials.