Calcium phosphate scaffolds for bone tissue engineering and self -association PEG-PLLA diblock copolymer for controlled drug delivery system.

Abstract

In scaffold-based bone tissue engineering, the existing three-dimensional scaffolds have proved less than ideal for actual applications, not only because they lack mechanical strength, but also because they do not guarantee interconnected channels. In this work, complex three-dimensional porous dicalcium phosphate dihydrate cement (DCPD) scaffolds with control interconnected pores were successfully manufactured by combining a computationally designed using an image-based approach and a fabrication technique by indirect solid freeform fabrication (ISFF) or 'lost mold' method via casting. The scaffold fabrication can be done at physiological temperatures; the macroporosity and interconnected pore network are incorporated while the microporosity is maintained. Therefore, it is possible for any biological factor such as growth factor or bone cell to be added during scaffold manufacturing. Calcium phosphate cement is a bioceramic with potential applications for bone-tissue engineering because of its excellent biocompatibility and bone-replacement behavior over long periods. Cement must be cast in complex molds to achieve specific design of macropores with chosen size and connectivity. Unlike the fluid ceramic slurries, the DCPD cement was a more viscous paste before setting. The thorough characterization of cement slip is investigated and optimized. The complex calcium phosphate cement scaffolds (macroporosity between 33%--70%) were thoroughly examined using a non-destructive micro-computed tomography. The effects of void variance and fabrication defects on mechanical properties of the scaffolds were evaluated and compared. Image-based finite element analysis was applied to predict the mechanical behavior of the designed and the fabricated scaffolds. The latter was subsequently mechanically tested. The computational prediction of effective stiffness constants and stress distribution of the scaffolds correlated well with the experiments and showed that the calcium phosphate cement scaffolds have mechanical properties that lie within the range of human trabecular bone. By employing an <italic>ex vivo</italic> gene therapy, scaffolds were then implanted subcutaneously to demonstrate tissue in-growth. The implanted scaffolds were evaluated histologically, mechanically, and using micro-computed tomography. The implant was found to be surrounded by a large amount of bone as well as within the scaffold pores at the four weeks time point. Almost the entire implant was enveloped by new bone after eight weeks of implantation. These techniques allow us to investigate the bone formation and the scaffold degradation both qualitatively and quantitatively. These results show that by integrating the computationally designed, biodegradable osteoconductive DCPD matrix, and <italic> ex vivo</italic> gene therapy, have potential for engineering of biomimetic scaffolds and scaffolds for complex biomechanical applications.