Objective: The aim was to investigate starch-gelatin hydrogels as scaffolds for chondrogenesis and compare these with other materials currently in use regarding cell retention and growth. Methods: Two variants of starch-gelatin-scaffolds and one chitosan-based scaffold were fabricated by casting and freeze-drying. The resulting materials were analyzed with respect to physicochemical and mechanical properties, cut to size, and seeded with human articular chondrocytes. Cell retention and proliferation were evaluated at 1, 14, and 42 days of culturing. Extracellular matrix production was analyzed by histo- and immunohistochemistry. Comparisons were made with that of commercially available hyaluronan- (Hyalofast ^® ) and collagen-based (ChondroGide ^® ) scaffolds, and synthesized chitosan hydrogels. Results: The starch-gelatin materials exhibited highly porous structures stabilized by hydrogen bonding, with swelling behavior similar to native cartilage and favorable mechanical handling properties. Despite differences in initial cell retention, all materials except chitosan supported robust cell growth, reaching similar levels after 14 days. No significant changes were observed between 14 and 42 days with the exception of Hyalofast ^® showing decreased cell number. Chitosan-supported cell growth was more linear over the culture period, but resulted in only half the cell number by day 42 compared with the other materials. Without cells, Hyalofast and one variant of the starch/gelatin hydrogel degraded before day 42. starch/gelatin scaffolds showed collagen I, II, and aggrecan deposition. Conclusion: Starch-gelatin scaffolds displayed favorable mechanical properties, supported cell growth comparable to commercial scaffolds, and promoted deposition of cartilage-specific extracellular matrix, highlighting their chondrogenic potential

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.