Solvent-Free Plasma-Assisted Synthesis of Hydroxyapatite Nanoparticles: Preparation, Characterization and Incorporation into Alginate Hydrogels.

In this work we explore a plasma-assisted, solvent-free synthesis of hydroxyapatite nanoparticles (HAp NPs) by exposing the precursors (i.e. CaCl2 and (NH4)2HPO4) solely to N2 and O2 plasma gases at different powers and treatment times. Depending on the plasma generation conditions, different calcium phosphate (CaP) phases are formed in addition to HAp, including octacalcium phosphate (OCP) and dicalcium phosphate dihydrate (DCPD). The conditions identified as the most favorable for the plasma-assisted synthesis of HAp, in terms of preferential formation of HAp over OCP and DCPD, reaction completion, and conversion efficiency of the reagents into HAp, consist of using O2 at 0.8 mbar as the working gas, with a plasma power of 50% and a treatment time of 300 s. HRTEM studies demonstrate that, under these operating conditions, plasma-assisted synthesis predominantly yields crystalline HAp nanoparticles (NPs) with average size of 5.5 ± 2.5 nm. The synthesized ultra-small HAp NPs are incorporated into Ca2+-mediated alginate (Alg) hydrogels to assess their potential as both nanofillers and crosslinking agents for improving hydrogel stability under Ca2+-free conditions. While the incorporation of HAp NPs does not significantly affect the hydrophilicity or overall structure of the Alg network, it markedly influences the stiffness and gelation process through the interactions between Alg carboxylate groups and the Ca2+ ions located in the HAp crystal lattice. The results demonstrate that ultra-small HAp NPs can function as secondary crosslinking agents, increasing the crosslinking density and strengthening the hydrogel network, when the Alg binding sites are not already saturated by Ca2+ ions supplied by CaCl2.