Abstract
Background/Objectives: 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. Methods: 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. Results: 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 Staphylococcus aureus. 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. Conclusions: Overall, these G-HAM provide a promising platform that integrates controlled antibiotic release with osteoconductive potential for bone infection treatment and tissue regeneration.