In this study, we successfully prepared porous composite microspheres composed of hydroxyapatite (HAp), di-calcium phosphate di-hydrated (DCPD), and chitosan through the hydrothermal method. The chitosan played a crucial role as a chelating agent to facilitate the growth of related calcium phosphates. The synthesized porous composite microspheres exhibit a specific surface area of 38.16 m²/g and a pore volume of 0.24 cm³/g, with the pore size ranging from 4 to 100 nm. Given the unique properties of chitosan and the exceptional porosity of these composite microspheres, they may serve as carriers for pharmaceuticals. After being annealed, the chitosan transforms into a condensed form and the DCPD transforms into Ca₂P₂O₇ at 300 °C. Then, the Ca₂P₂O₇ initially combines with HAp to transform into β tricalcium phosphate (β-TCP) at 500 °C where the chitosan is also completely combusted. Finally, the microspheres are composed of Ca₂P₂O₇, β-TCP, and HAp, also making them suitable for applications such as injectable bone graft materials.

Hydroxyapatite—gelatin microspheres with cone-like pores were synthesized via the wet-chemical method using ammonium dihydrogen phosphate ((NH₄)H₂PO₄) and calcium nitrate (Ca(NO₃)₂·4H₂O) as a source of calcium and phosphate ions with the addition of gelatin, which proved to be more osteoconductive than commercial products, such as fibrin glue and Osteoset^® Bone Graft Substitute. Following the method of the previous study for loading paclitaxel (PTX), a drug entrapment efficiency of around 58% was achieved, which is much lower than that of the doxorubicin (DOX)-loaded one. Since PTX is hydrophobic while DOX is hydrophilic, the order of chitosan processing and addition of the solvent were tuned in this study, finally leading to an increase in drug entrapment efficiency of 94%. Additionally, the release duration of PTX exceeded six months. The MTT assay indicated that the effect of drug release on the suppression of cancer cells reached more than 40% after one week, thereby showcasing PTX’s capacity to carry out its medicinal functions without being affected by the loading procedures.

Porous chitosan/hydroxyapatite (Chi-HAp) composite microspheres were prepared in an aqueous solution containing chitosan, calcium nitrate, and ammonium dihydrogen phosphate by using a hydrothermal method at various temperatures. The investigation indicated that temperature significantly impacted the final product’s appearance. Hydroxyapatite (HAp) coupled with dicalcium phosphate dihydrate (DCPD) flakes were obviously found at 65 and 70 °C, while the latter gradually disappeared at higher temperatures. Conversely, synthesis at 90 °C led to smaller particle sizes due to the broken chitosan chains. The microspheres synthesized at 75 °C were selected for further analysis, revealing porous structures with specific surface areas of 36.66 m²/g, pores ranging from 3 to 100 nm, and pore volumes of 0.58 cm³/g. Vancomycin (VCM), an antibiotic, was then absorbed on and released from the microspheres derived at 75 °C, with a drug entrapment efficiency of 20% and a release duration exceeding 20 days. The bacteriostatic activity of the VCM/composite microspheres against Staphylococcus aureus increased with the VCM concentration and immersion time, revealing a stable inhibition zone diameter of approximately 4.3 mm from 24 to 96 h, and this indicated the retained stability and efficacy of the VCM during the encapsulating process.

Cisplatin, a widely used chemotherapeutic agent, is limited by its poor bioavailability, rapid systemic clearance, and severe side effects. To overcome these limitations, hydroxyapatite–gelatin composite microspheres were developed to improve drug entrapment efficiency (DEE) and provide sustained drug release. Various formulations were prepared by incorporating chitosan either by mixing once or through a sequential coating strategy. By adjusting the loading procedure, the DEE increased from 58% to 99%. The composite microsphere effectively controlled the total drug release duration, extending it from one month to over 5 months. Moreover, the MTT assay demonstrated that all samples effectively inhibited cell growth, with cell viability reduced to less than 20% after 2 weeks of experimentation. These findings demonstrate that the sequential chitosan coating method offers superior drug entrapment and prolonged release compared to mixing chitosan once, exhibiting its potential as a sustained drug delivery system for cancer treatment.

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.