Physicomechanical, In Vitro and In Vivo Performance of 3D Printed Doped Tricalcium Phosphate Scaffolds for Bone Tissue Engineering and Drug Delivery

Thesis (Ph.D.), Materials Science and Engineering Program, Washington State UniversityAlthough tricalcium phosphate (TCP) is widely used in bone tissue engineering, the strength degradation kinetics is not well controlled. This study focuses on the underlying mechanism of strength degradation kinetics by incorporating trace elements in TCP. The objective of this research is to modify the mechanical properties of TCP to achieve the desired degradation rate for the specific need, and improve the in vivo bioactivity for early wound healing by incorporating trace elements such as strontium (Sr2+), magnesium (Mg2+) and silicon (Si4+) as dopants. The hypothesis of this research is that the presence of different trace elements in TCP will influence its phase stability, microstructure, mechanical strength, and both in vitro and in vivo bioactivity. Direct three dimensional printing (3DP) was used to fabricate designed interconnected macroporous pure and doped TCP scaffolds. Microwave sintering as opposed to conventional sintering was also used for better densification and higher mechanical strength. A maximum compressive strength of 10.95 ± 1.28 MPa and 12.01 ± 1.56 MPa were achieved for pure and Sr2+-Mg2+ doped TCP scaffolds with 500 μm designed pores (~400 μm after sintering) sintered in microwave furnace, respectively. Substitution of Mg2+ and Sr2+ into calcium (Ca2+) sites of TCP crystal lattice contributed to phase stability and controlled gradual degradation. On the other hand, Si4+ substitution into phosphorous (P5+) sites destabilized the crystal structure and accelerated degradation of TCP. Interconnected macroporous β-TCP scaffolds facilitated in vivo guided bone tissue regeneration through infiltration of cells and extracellular matrix into the designed pores. Presence of Sr2+, Mg2+ and Si4+ into β-TCP induced increased in vivo early bone formation and better bone remodeling through increased extracellular matrix production such as, collagen and osteocalcin, when tested in rat and rabbit distal femur model. The presence of Si4+ along with Mg2+ induced increased new blood vessel formation. Our results exhibited that Sr2+, Mg2+ and Si4+ doped 3DP TCP scaffolds have strong potential in bone tissue engineering applications for early wound healing.Department of Materials Science, Washington State Universit