Chitosan–Hydrazone-Modified Calcium Phosphate Scaffolds: Fabrication, Characterization, and Drug Delivery Potential

<b>Background/Objectives</b>: Recent advancements in biomaterials aimed at closely mimicking natural biological tissues hold great promise for hard tissue regeneration and controlled drug release due to their superior physical, chemical, and biological properties. This study aimed to develop multi-ion doped calcium hydroxyapatite (HAp) scaffolds with chitosan-based coatings for localized drug delivery, incorporating a novel hydrazone compound with potential anticancer activity. <b>Methods</b>: HAp powders doped with magnesium (Mg²⁺), strontium (Sr²⁺), and varying fluoride (F^-) contents (0-2 mol.%) were synthesized via a hydrothermal method. Scaffolds were fabricated using the sponge replica technique and subsequently coated with chitosan or a chitosan-hydrazone blend. Dopant incorporation was confirmed by electron dispersive X-ray spectroscopy (EDS). Phase composition and morphology were analyzed via X-ray diffraction (XRD) and scanning electron microscopy (SEM). Mechanical properties, bioactivity, cytotoxicity, and hydrazone release profiles were systematically evaluated. <b>Results</b>: EDS confirmed successful incorporation of Mg²⁺ and Sr²⁺ in all powders, while F^- was detected only in powders with 1 and 2 mol.% fluoride. XRD and SEM revealed the phase composition and scaffold microstructure. Chitosan coatings significantly improved scaffold compressive strength and reduced degradation rate, indicating enhanced stability in biological environments. The coated scaffolds supported MRC-5 fibroblast viability. The hydrazone compound exhibited dose-dependent antitumor cytotoxicity comparable to cisplatin and showed sustained release from scaffolds for up to 15 days. <b>Conclusions</b>: The combination of multi-ion doped HAp scaffolds and chitosan-hydrazone coatings provides a promising platform for bone tissue engineering and localized cancer therapy, demonstrating both mechanical stability and controlled, sustained drug release.