SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL ACITVITY OF ALUMINUM SUBSTITUTED HYDROXYAPATITE AND AMORPHOUS CALCIUM PHOSPHATE

Hydroxyapatite (HA; Ca10(PO4)6(OH)2) is an inorganic crystalline material found in biological hard tissues, such as bone and teeth. Biogenic HA is non-stoichiometric and has varying crystallinity and ionic substitutions depending on the function and anatomy of the tissue within which HA occurs. HA is also found in pathological calcifications, such as microcalcifications (MCs) found in breast cancer tissues. HA MCs with lower carbonate substitution have shown to be related to more invasive (malignant) breast cancer tissue specimens, suggesting pathological connections to ionic substitutions in HA. Recently, aluminum substitution in HA MCs was identified but its connection to cancer progression remains unclear. To further understand aluminum substitution in HA and its relevance to cancer, aqueous synthesis and thorough characterization of aluminum substituted HA (Al-HA) was done via powder X-ray diffraction, Fourier-transform spectroscopy, X-ray photoelectron spectroscopy and electron microscopy (SEM, TEM). With increasing concentrations of aluminum in particle synthesis morphologies of particle became elongated and thinner compared to a rod-like shaped HA particle morphology. Also with high concentrations of aluminum inclusion, particles no longer maintained long-range crystalline order, and aluminum substituted amorphous calcium phosphate (Al-ACP) was formed. Utilizing the synthesized HA, Al-HA, and Al-ACP particles, three-dimensional porous poly(lactic-co-glycolic acid) cell culture scaffolds were fabricated to mimic the microenvironment of aluminum substituted MCs found in breast tissues. Breast cancer cells (MDA-MB231) were seeded and cultured in vitro to assess the effect of Al-HA and Al-ACP on cell adhesion. Compared to blank scaffolds, cells adhered better on HA and Al-HA containing scaffolds. Whereas, compared to HA containing scaffolds, cells adhered less on Al-ACP containing scaffolds. This research lays the groundwork for future studies to investigate the role of Al-HA in breast cancer diagnosis and prognosis