(Ca/Zn)CO₃ Microparticles Loaded with BacitracinAntibacterial and Osteogenic Dual Action Carriers

Calcium carbonate (CaCO₃) microparticles are widely used in biomedical engineering, mainly in the field of bone tissue regeneration. This study aimed at the development of CaCO₃-based carriers for an antimicrobial peptide, bacitracin (BCT), with antibacterial and osteogenic properties. The first part of the study was devoted to CaCO₃ microparticles obtained by the precipitation method from equimolar Na₂CO₃ and CaCl₂ solutions. The morphology, size, and surface area of the microparticles were strongly dependent on the parameters used during the reaction (i.e., the mixing speed and geometry of the container). However, BCT adsorption on CaCO₃ microparticles was insufficient (maximum drug loading of approximately 1%); therefore, the microparticles were enriched with Zn²⁺ ions (5%, 10%, or 20% vol. of the CaCl₂ solution used for precipitation was exchanged to equimolar ZnCl₂ solution). This innovative approach significantly influenced the properties and BCT adsorption capacity of the microparticles. The microparticles containing Zn²⁺ were larger and cubic in shape with a predominant calcite structure. The adsorption efficacy of BCT increased significantly (maximum drug loading of approximately 40%) due to the strong affinity of BCT to Zn²⁺. BCT was released from the microparticles within 24 h, and the degradation of Zn²⁺ containing microparticles was three times slower than in the case of nonmodified CaCO₃ microparticles. The microparticles were cytocompatible with L929 fibroblasts and human mesenchymal stem cells (hMSCs), except for the microparticles with the highest Zn²⁺ content. The microparticles with adsorbed BCT successfully inhibited the growth of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. (Ca/Zn)-CO₃ microparticles enhanced osteogenic differentiation of hMSCs; however, this effect should be attributed to the release of Zn²⁺ rather than BCT. The newly developed (Ca/Zn)-CO₃ microparticles with adsorbed BCT could in the future serve as antibacterial and osteogenic materials for the treatment of bacterial infections and regeneration of bone tissue.