Controllable Fabrication And Characterization Of Porous Calcium Phosphate Scaffolds For Bone Tissue Engineering

The statement and development of bone tissue engineering have changed the traditional treatment modes for bone defects, and also put forward higher requirements for scaffolds fabrication. However, the ceramics scaffolds fabricated so far exsit some problems, such as relatively low strength, uncontrollable inner structures and the contradition between sintering and performances, which greatly limit their clinical applications. Scaffold is one of the key elements of bone tissue engineering. The fabrication of its three-dimensional fine structures is largely depended on preparation techniques. With the development of solid freeform fabrication, extrusion deposition technique (EDT), a representative of direct writing, shows great advantages on manufacturing micro-nano bio-devices due to its highly applicability and flexibility. Combined with microwave rapid sintering, EDT provides a powerful mean to solve the above problems in bone scaffolds fabrication.The objective of this paper is to establish a controllable process for bone scaffold fabrication based on motor assisted microsyringe extrusion deposition technique and microwave sintering, to meet the structural, mechanical and biological requirements of porous calcium phosphate bone scaffolds. The effects of structure and sintering process on the mechanical, degradative and biological properties of scaffold were investaged, according to materials test, biological evaluation, computer simulation and theoretical analysis. Methods for scaffold controllable preparation and performance optimization were proposed.According to the requirements of slurry for EDT, nano HA slurry with high concentration, good dispersibility and stability were prepared. The dispersal mechanism of nano particles was expounded. The results showed that the slurry prepared from20nm HA ceramic powder was able to obtain good dispersion stability under the conditions of PH=9.0,1wt%dispersant agent PAA-NH4(compared to the weight of HA). The slurry with volume concentration of25-40vol%has good self-support capability and proper solidification rate, that can be used for extrusion deposition process.A new process based on motor assisted microsyringe extrusion deposition technique and microwave sintering was developed for scaffold controllable fabrication. The mathematical model of the slurry flow in the nozzle and the parameters matching model of EDT were established. The sintering process was also optimized. Porous HA scaffolds with different outer shapes like cubic, cylinder and tibia bone, and different pore structures like triangle, square and hexagon were fabricated. The structure features of scaffolds are controllable, and their porosities are adjustable as well. The scaffolds have good connectivity. The microwave sintered scaffolds (1200℃,40℃/min,30min) gain uniform shrinkage with an average shrinkage rate about31.8%. They also gain high density and fine grain size (1.12±0.23μm) in the rods. The compressive strength test shows that microwave sintering is conducive to the improvement of mechanical strength of porous scaffolds. The average compressive strength of microwave sintered scaffolds with porosity of50%is45.57MPa, much higher than that of the conventional sintered ones.Finite element analysis and experimental results show that scaffold structure affects the load capacity by changing their stress intensity and distribution. The weight relationship of the impact of structure features on mechanical property is porosity> pore size> pore shape. For a uniform structure scaffold, the quantitative relationship between compressive strength and porosity inσ=ln432.3-4.825p.In order to further improve the mechanical strength, porous scaffold strengthened with micro-ribs was also designed and controllably fabricated. The average compressive strength is84.2MPa (porosity about50%), about80%higher than the scaffolds without micro-rib with the same porosity, and close to the strength of the cortical bone. Moreover, it also exhibits more stable mechanical strength during degradation in vitro, which could provide longer support for cell proliferation and tissue formation. The fracture mechanism of porous ceramic scaffold is cleavage. Scaffold will crack from the rod joint where the tensile stress concentrated.In vitro degradation and cell scaffold co-culturing experiments results show that the porous scaffold could slowly dissolve and release Ca2+in saline. It also could generate bone-like apatite layer in SBF. The fabricated scaffold has good biocompatibility. Cells could adhere to the outer surface, side walls and interal surface quickly and form a tightly biological adhesion to promote proliferation and growth. The microwave sintered scaffold possesses finer grains and better degradation ability than conventional sintering scaffold due to short sintering time and high heating rate, which could promote the adhesion and proliferation of osteoblast.As a conclusion, extrusion deposition technique, a representative of direct writing, combined with microwave sintering could achieve personalized fabrication of scaffold with improved mechanical and biological properties, which could solve the clinical application problems of calcium phosphate ceramic and enrich the biofabrication methods.