| The history of the restoration of injured tissues using biomaterials can be traced back tothe prehistoric period, dating back30,000years. There is evidence revealing that the Chineseand the Romans used gold for false teeth as long as2000years ago. Currently, orthopedicreconstruction procedures stemming from trauma, tumor, deformity, degeneration and anaging population have dramatically increased, triggering a high demand on the advancementof bone implant technology. According to the2009Asia Audit report released by theInternational Osteoporosis Foundation (IOF), there are almost69.4million people over theage of50suffering from osteoporosis in the mainland of China, resulting in some687,000hipfractures and1.8million new vertebral fractures occurring per year. Over the past fourdecades, the number of hip fractures increased by300%in Hong Kong and by about500%inSingapore. In Japan, the prevalence of osteoporosis is around12million and the hip fractureincidence rate in the oldest population (over75) is increasing dramatically in both men andwomen. TechNavio’s analysts have forecasted that the global orthopedic contractmanufacturing market will grow by11.05%of CAGR between the years2012and2016.Increased use of reconstruction procedures in orthopedics, due to trauma, tumor, deformity,degeneration and an aging population, has caused a blossom, not only in surgicaladvancement, but also in the development of bone implants. However, there are somedrawbacks in the current scaffolds. a). Due to the more complex structure required for thicker,three-dimensional tissues, science is some way off generating a defnitive clinical product fortissues such as bone. This is largely due to the non-homogeneous growth of cells on thetraditional―porous block‖scaffolds, which prevents the formation of a functional constructfrom surface to core. This in turn is due to the mass transfer limitations of the porousstructures into which cells are expected to migrate and populate. The movement of nutrientsto, and waste products from the cells in the pores relies on molecular diffusion; nutrients areused up before reaching the inner core of the construct and waste products build up. Cells thatdo migrate into the core become necrotic and so the cell population are commonly found to beconcentrated at the periphery of the scaffold. b). Preformed polymeric scaffolds have received attention in the area of bone reconstruction because they provide a temporal and spatialenvironment for new bone tissue ingrowth. However, these preformed scaffolds have theirdrawbacks, as demonstrated in animal tests and clinical applications. Issues such as: reducedmechanical properties, poor surgical performance, and morphological mismatch withirregularly-shaped defects, have been observed. In this study, we have tried to overcome theseproblems.Section1. The3D porous scaffold with micro channels fabricated by phase separationwas used in rabbit radius bone defect repair. In order to overcome the block of materialexchange of the traditional scaffold, a novel kind of porous scaffold with micro channels wasdesigned and fabricated by the method of phase separation. In detail, a certain amount of thePLGA and HA (Nanjing Emperor Nano Material Co.,Ltd, China)(HA: PLGA (w/w)=1:9)were added to NMP (Aladdin Industrial Co., Ltd, China). After being sealed in conical flask,the composite (PLGA/HA/NMP) was heated to70°C for3h to promote PLGA dissolution.Then, the composite was fabricated by blending sodium chloride as a porogen (200-300μm).Then the composite was laid in homemade molds and immersed in water for72h. Finally thescaffold was obtained after frozen-dried. SEM showed that mocrichannels were distributed inthe pore surface and cross-section. The size of the micro channels is approximately1μm,which is in favor of materials’ exchange. The compression testing showed that the mechanicalstrength can reach to1-4MPa. The scaffold improved cell proliferationwhich was muchhigher than the scaffold fabricated by mould molding method. Furthermore, the PS scaffoldhas better ability to induccell differentiation because of much more HA explorsion. Theanimal test showed that PS scaffold possessed better capacity of mineralization than MMscaffold because of more quantity of new bone formation in PS scaffold.Section2: The injectable PLGA/HA/GMs composites were fabricated and applied oncalvarial bone defect. In order to figure out the issues that reduced mechanical properties,poor surgical performance, and morphological mismatch with irregularly-shaped defects, wefabricated injectable PLGA/HA/MGs composite with uncross-linked GMs as porogen andrhBMP-2delivery system. In detail, a certain amount of the PLGA and HA mixtures wereadded to NMP. After being sealed in conical flask, the composite (PLGA/HA/NMP) washeated to70°C for3h to promote PLGA dissolution. Then, the injectable scaffold wasfabricated by blending GMs and GMs/rhBMP-2as a porogen (200-300μm). The mechanicalstrength of tht hardened scaffolds can be regulated to fit the application. The animal testshowed that the injectable scaffold possessed good capacity of mineralization and osteogenesis, especially after carrying rhBMP-2. Although the NMP was involved in theinjectable scaffolds, no tissue damage appeared in heart, lung, liver, spleen and kidney.Section3: The injectable4D scaffold was fabricated and applied on rabbit bone defectrepair. The preformed scaffolds have their drawbacks, as demonstrated in animal tests andclinical applications. Issues such as: reduced mechanical properties, poor surgicalperformance, and morphological mismatch with irregularly-shaped defects, have beenobserved. It motivated the development of novel injectable systems that can fill defects well,allowing in situ solidification within the host while retaining high initial mechanical strengthand appropriate porosity. In this study, a four-dimensional (4D) scaffold was fabricated byincorporating gelatin microspheres (GMs) into a PLGA-based injectable implant. This wasdone to create an in situ morphological match and to accomplish time-dependent poreformation as GMs degradation. The special scaffold displayed a nonporous design in itsbaseline configuration to provide high strength early in the application period; a gradual,time-dependent, pore-forming process follows this initial stage to provide space for cellinvasion. We expect our work can lay the foundation for the production of a4D injectableimplant that aids the healing process by maintaining mechanical support during active bonetissue ingrowth.In the studies, we have developed the traditional3D scaffold successfully.1. We havedesigned and prepared the porous scaffold with micro channels which were favorable formaterial exchange and further improved bone regeneration;2. We have designed injectable3D scaffold to fit the undesired irregular bone defects;3. We designed and fabricatedinjectable4D bone tissue engineering scaffold. The special scaffold displayed a nonporousdesign in its baseline configuration to provide high strength early in the application period; agradual, time-dependent, pore-forming process follows this initial stage to provide space forcell invasion. |
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