Copper-Modified Antibacterial Hybrid Hydroxyapatite/Methylcellulose/Chitosan Granules: Self-Assembly & Enhanced Properties

: Granular materials and microspheres have emerged as promising platforms for regenerative medicine, due to their ease of handling, their ability to be used as standalone materials or as part of composites, and their ability to provide structural support while allowing controlled delivery of therapeutic agents. In this study, self-organizing hydroxyapatite–methylcellulose (HAp–MC) granules modified with varying amounts of chitosan (CTS) were developed and systematically investigated. Copper ions and copper oxide nanoparticles were added as agents that promote antibacterial activity. The results demonstrate that the chitosan content does not affect the self-assembly process, which is governed by a methylcellulose-mediated mechanism. Spectroscopic and thermal analyses showed that the materials belong to class I hybrids, stabilized by weak intermolecular interactions such as hydrogen bonding and electrostatic forces. The structural stability and hybrid nature of the material arise from intermolecular interactions, physical cross-linking, and coordination with divalent cations (Ca 2+ and Cu 2+ ), as well as the nanometric size of the hydroxyapatite grains. Mechanical testing revealed that the presence, type, and content of polymer significantly influence the compressive strength. Materials containing methylcellulose and chitosan exhibited superior performance as a result of intermolecular interactions between the components, whereas a decrease in compressive strength was observed for copper-modified materials. In vitro studies in simulated body fluid confirmed the bioactive potential of the materials. The results of antibacterial tests revealed that all copper-containing granules exhibited significant antibacterial activity, attributed to the synergistic action of copper and chitosan. These results show the potential of copper-modified hybrid granules for bone regeneration combined with effective infection prevention. However, further in vivo evaluation is required.