Inhibiting Effects of Antibiotic-Loaded Porous Gelatin-Hydroxyapatite Microspheres on Staphylococcus aureus

<b>Background/Objectives:</b> Due to their biocompatibility and bone-like composition, calcium phosphate materials-especially hydroxyapatite (HAp)-have emerged as promising carriers for localized antibiotic delivery in bone regeneration. Here, we developed Hap-based composite microspheres using a simple wet-chemical method and incorporated multiple antibiotics to evaluate their release profiles and antibacterial potential for treating bone infections. <b>Methods:</b> In this study, uniform and porous composite microspheres composed of Hap and gelatin were synthesized via a simple wet-chemical method using a mixed calcium phosphate-gelatin solution. <b>Results:</b> The resulting gelatin-Hap microspheres (G-HAM) were systematically characterized to verify their crystalline structure, morphology, composition, and thermal stability. G-HAM exhibited a highly porous structure, making them well-suited for use as drug carriers. Four clinically relevant antibiotics-gentamicin, vancomycin, teicoplanin, and zyvox-were incorporated into the microspheres and evaluated for their release behavior and antibacterial performance against <i>Staphylococcus aureus</i>. The release profiles revealed an initial burst release within the first hour that exceeded the minimum inhibitory concentrations of all tested antibiotics, followed by a sustained release phase. Antibiotics containing carboxylic groups, such as vancomycin and teicoplanin, demonstrated stronger interactions with Hap, resulting in a more prolonged release. Antibacterial testing confirmed that the released antibiotics maintained their chemical stability and bioactivity. Furthermore, the combination of bioactive Hap and peptide-rich gelatin promoted osteoblast-like cell adhesion and proliferation, while cytotoxicity assays verified excellent biocompatibility. <b>Conclusions:</b> Overall, these G-HAM provide a promising platform that integrates controlled antibiotic release with osteoconductive potential for bone infection treatment and tissue regeneration.