| Every year, millions of people are suffering from bone defects arising from trauma, tumor or bone related diseases and of course several are dying due to insufficiency of ideal bone tissue. Biologically produced bone structures are known for self healing. However, large bone defects do not heal spontaneously and require surgical intervention for restoration, and the current therapies include autografts, allografts. Nonetheless, autografts maybe associated with donor shortage and donor site morbidity whereas allografts may have the risk of disease transmission and immune response. The aforesaid limitations and the expected shortage of bone grafts for surgical procedures, motivated materials scientists to find suitable bioactive materials, such as three-dimensional (3D) porous scaffold designed with the required porosity, mechanical strength and a favorable environment for bone cell attachment, to provide mechanical stability in the defect region and launch tissue regeneration with specific living cells. With the rapid development of bone biomaterials, great progress has been made in the last decade. However, as advancements are made, new challenges also emerge, which comes from the bone defect clinical requirements on the bone substitutes, In this paper, the multiphasic calcium phosphate was systematic studied, then the porous scaffold with good mechanical strength and biological properties based on calcium phosphate matrix was prepared with suitable preparation method, the properties of scaffold in vitro and in vivo were studied last, the main achievements were summarized as follows:1. The HA paricles was needle-like prepared by wet chemistry, and the TCP paricle was irregular shapes, furthermore, TCP was amorphous state at room temperature, and transform to P-TCP after800℃sintering. The multiphasic calcium phosphate could be prepared by wet chemistry with controlling of pH, Ca/P, and sintering temperature. The sintering temperature was at600-800℃, the calcium-deficient apatite (CDA) powder was obtained, and the multiphasic calcium phosphate powder was obtained at1200℃. While the pH at6.5and10.5, the crystallinity degree of calcium phosphate was increased with the increase of Ca/P ratio, basically composed of HA and β-TCP phase. While the pH at7.5-9.5, the CDA phase was existed except for HA and β-TCP at1.55of Ca/P ratio, furthermore, the more three calcium phosphate phase was found while the Ca/P ratio was at1.60and1.75with good crystallinity, and the calcium phosphate was composed of HA and CDA phase while the Ca/P ratio was at1.65and1.70. The multiphasci calcium phosphate particle was needle-like, and the paricles morphology was changed with the increase of sintering temperature, rodlike at600℃, elliptical at800℃, and irregular at1200.2. The HA/(HA+β-TCP) ratio in biphasic calcium phosphate was mainly controlled by pH and Ca/P ratio. With the increase of pH, the HA concentration of BCP was increased with the decrease of β-TCP concentration. At the same pH conditions, the BCP possess the highest HA concentration while the Ca/P ratio at1.65, furthermore, while the Ca/P ratio was close to1.65, the BCP powder with high HA concentration could be obtained.3. A well-developed BCP/PVA scaffold with interconnectivity, porosity, and moderate compressive strength as well as good biocompatibility was fabricated by emulsion foam freeze-drying method for bone tissue engineering. The pore size (50-700μm), porosity (73-87%), and compressive strength (0.19-0.26MPa) could be controlled by weight ratio of BCP/PVA. Furthermore, the prepared scaffolds showed the lower variation of pH values (approximately7.18-7.36) in SBF solution, and an increase of porosity led to the increase of the biodegradation rate for BCP/PVA scaffolds. In addition, the BCP/PVA porous scaffold has good cytocompatibility, showing no negative effects on cells growth and proliferation. The porous structure, hydrophilicity, and mechanical strength of the BCP/PVA porous scaffold can meet essential requirements for bone tissue engineering and regeneration. 4. The3-D porous HA/PLLA nanocomposites coated BCP scaffolds with interconnectivity, high compressive strength and improved bioactivity has been fabricated and tested for repairing the large necrotic lesions in the loading-bearing region of rabbit femoral head using tissue-engineering technology. The compressive strength of BCP scaffold was increased to3.35-3.95MPa by HA/PLLA nanocomposites coating. Furthermore, based on unchanging interwork porous structure, the microstructure of pore wall on coated scaffold was formed, which lead to promote cell adhesion and proliferation. In addition, the developed scaffolds showed the capacity of bone regeneration combined with hBMSCs for large necrotic lesions in the rabbit femoral head. This study suggests a new strategy for use of nanocomposites coated scaffolds combined with hBMSCs, which can support cell adhesion and bone regeneration effectively and constantly for load-bearing bone tissue engineering application.5. A well-developed BCP scaffolds coated with multi-layer of HA/PLLA nanocomposites with interconnectivity, high porosity, and moderate compressive strength as well as good biocompatibility were fabricated for bone tissue engineering. After coated with HA/PLLA nanocomposites, the scaffolds maintained the BCP framework structure, and the porous network structure of scaffolds remained unchanged, however, the compressive strength was increased with the increase coating layer number of HA/PLLA nanocomposites. The prepared scaffolds showed the lower variation of pH values in SBF solution, and an increase of coating layer number led to the decrease of the biodegradation rate at different days. Moreover, the multi-layer coating scaffolds had good cytocompatibility, showing no negative effects on cells growth and proliferation. Furthermore, the bone-like apatite layer was built obviously in the interface of scaffold after21days post-implantation in SD-rat muscle. In conclusion, the BCP scaffold coated with multi-layer of HA/PLLA nanocomposites could be a candidate as an excellent substitute for damaged or defect bone in bone tissue engineering.6. Bioactive BCP scaffold coated with HA/PLLA nanomposites were prepared and modified by immersing in simulated body fluid to obtain the biomineralized materials for bone tissue engineering. The formation of mineralites was observed by SEM analysis, however, differ from literature, the NaCl apatite was identified by surface analyses at first stage and then Ca-P apatite with colloidal HA nanoparticles appeared and growed after increasing immersion time in SBF, subsequently, the bone-like apatite was detected until28days. At supersaturated SBF conditions, the deposition rate of scaffold was improved, and the deposition morphology of scaffold was similar to1×SBF fluid. The scaffold modified by biomimetic method was treated by low temperature freeze at-20℃, the micropore was formed on the pore wall, the micropore size was about3-5μm, furthermore, the calcium ion was substituted by magnesium and potassium ion in calcium phosphate to form the biological bone-like apatite.7. The linear PLGA-mPEG microspheres loaded with different drugs was prepared by multiple emulsion method. Through UV spectrophotometer, the standard curves of BSA and vancomycin was comfirmed. The copolymer degradation rate could be controlled by controlling of LA/GA molar ratio, to the control the release rate of drugs loaded on the kind of compolymer microspheres. Furthermore, the types of drugs could be loaded on the PLGA-mPEG microspheres, and the sequential control release of two drugs could be achieved.8. Through the toxicology test analysis, the BCP scaffold coated with HA/PLLA nanocomposites possess nontoxic properties, accord with medical apparatus and instruments standards. While the scaffolds were implanted in muscle, the experiments animal have not showed any abnormal activities, and the bone-like apatite layer was built obviously in the interface of scaffold. After the bone defect repair experiments, the new bone was formed gradually in the interface of scaffold while the scaffold was implanted in the bone defect part, at the same time, part of scaffold was degraded. There were still a few of unabsorbed scaffolds observed at some areas after2months postsurgery. They were mainly on the sides of newly formed radius and some of them were wrapped with new bone callus. The scaffolds were destroyed into small separated pieces and wrapped with invaded fibrous tissues. Most of them were hard to be distinguished except some areas. The coated scaffolds appeared to be osteoconductive and supported osteointegration and bone deposition, and also showed the osteophilicity, thus promoting medullary bone formation along the implants. |
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