Compositional and structural control at nanoscale for bone implant: Whitlockite and Nanochannel

Abstract

Naturally existing hard materials, such as bone in the hard tissue of the living system, are hierarchically self-assembled by nanoparticles which are thermodynamically the most stable state. Inspired from these biominerals, previous researchers have been successfully made similar artificial materials in micrometer scale and applied into various fields. However, investigation of biominerals in nanometer scale is still remained a challenge and thus the related effects in living organism are unclear. Therefore, in this thesis, we discussed about compositional and structural control at nanometer scale for bone implant in order to understand and recreate natural minerals. In the first part of the thesis, in order to develop similar structure to bone, we discussed about whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) which is one of the most abundant inorganic phases in bone along with hydroxyapatite (HAP: Ca10(PO4)6(OH)2). Until now, most of the previous researches related to the bone implant had been conducted by utilizing HAP because WH was difficult to be synthesized in physiologically relevant condition. Here, we described large-scale synthesis of pure phase of WH nanoparticles in ternary Ca(OH)2-Mg(OH)2-H3PO4 aqueous system based on the systematic approach. In addition, we showed material properties of synthesized WH compare to its synthetic analogue tricalcium phosphate (TCP: Ca3(PO4)2). During synthesis process, kinetic mechanism of the precipitated WH was analyzed to comprehend the formation mechanism of WH in our body system. Although, HAP is most stable at above neutral pH, as the pH of the synthetic system changed from basic to acidic environment, it dissolved and transformed into newly stable WH structure based on the dense construction of Ca2+ and PO43- ions around Mg2+ and HPO42- in the center of ions. When WH was fabricated into scaffold, it showed higher cellular proliferation rate than well-known HAP and TCP implant materials in the in vitro test. The human bone cells grown on the surface of WH also actively involved in the bone mineralization process showing an excellent biocompatibility. In addition, based on the strong mechanical property of WH compare to that of HAP and TCP, WH was easily produced into various types of implants. It also showed high capability to co-exist with free fluoride ions which can be further used as a toothpaste material. In this regard, WH had high potential to be applied in various fields as a biomaterial. In the latter half of the thesis, to recreate bone-like structure in nanometer scale, we designed and fabricated dimension tunable nanochannel with its width changed from micrometer scale to nanometer scale in HAP scaffold. Tree-like pore networks in nanometer scale are well known for the most optimized structure to maximize capillary effect and thus to occur efficient supply. Especially, tapered channels are simultaneously good at permeability from its wide entrance which also induces fast circulation. In this research, we applied additional pressure energy during the sintering process to induce phase separation between polyethylene glycol polymer and HAP nanoparticles. Notably, pressure energy was gradually increased to make different levels of phase separation which changed dimension of the nanochannel. The resulted well Aligned Multiple Capillary networks with gradually decreasing Diameter were directly observed by FIB-FESEM, TEM, Nano-CT analyses and confirmed that these networks were continuously connected with each other. In addition, the capillary power was found to be stronger when the direction of the decreasing dimension of the channel was parallel to the supply direction of the fluid than when it was placed in the opposite direction. Remarkably, small organisms such as human cells and bacteria were able to proliferate at the end of the nanochannels, solely depending on the nutrients supply through the nanochannel, indicating the significance of the nanochannels in the living system. The compositional and structural control at nanometer scale for bone implant in this thesis will be useful to understand the formation mechanism and the role of biomineral in the living system. We believe that this study will directly contribute to make more bone-like implants and provide inspiration and foundation knowledge to the other various research fields related to nanometer scale.