Functionalized Calcium Phosphates with Anti-Resorptive, Anti-Angiogenetic and Anti-Bacteric Properties

Abstract

This PhD thesis was addressed to study the interaction between calcium phosphates and several functionalizing agents, in order to develop new materials with enhanced biological performance, suitable for biomedical applications in the orthopedic field. The functionalizing molecules taken into consideration include several bisphosphonates, namely risedronate, zoledronate, and alendronate, and a molecule from the large group of flavonoids, quercetin (3, 3’, 4’, 5, 7-pentahydroxy-flavone). Functionalization of several calcium phosphates, namely hydroxyapatite, octacalcium phosphate and anhydrous dicalcium phosphate (monetite), was performed following different strategies: direct synthesis and adsorption from solution. In particular, the study carried out on risendronate adsorption on four hydroxyapatites with different composition provided useful information on the influence of the characteristics of the supports on the mechanisms of adsorption and release of the bisphosphonate. The materials developed during these three years include also octacalcium phosphate at different content of alendronate, as well as octacalcium phosphate at different content of zoledronate, and coatings of mixed composition, octacalcium phosphate – calcium alendronate, which were deposited on titanium substrates using Maple Assisted Pulsed Laser Evaporation. Quercetin functionalized hydroxyapatite was obtained thanks to a modified method of synthesis, which implies phase transformation from monetite, as well as through adsorption from solution. Adsorption from solution was successfully applied also to load the flavonoid on alendronate functionalized hydroxyapatite, monetite and monetite with a partial substitution of strontium to calcium ion. Finally polydopamine coating of octacalcium phosphate and α-tricalcium phosphate was utilized to induce reduction of silver ions and decorate the calcium phosphates with silver nanoparticles- Most of the developed materials have been submitted to biological in vitro tests, displaying both the beneficial properties (anti-osteoporotic and/or anti-inflammatory and/or anti-tumoral and/or anti-microbic) of the functionalizing agent(s) and the excellent bioactivity of the inorganic phase.