Modulating gentamicin release from Poly(lactic acid) composite matrices by tuning shell-derived calcium carbonate content for local antibacterial delivery

Controlling the release of hydrophilic antibiotics from biodegradable polyester matrices remains a key challenge in local antibacterial delivery. Here, we investigated whether gentamicin sulfate release from compact hot-pressed poly (lactic acid) (PLA) matrices can be modulated by varying the content of a shell-derived biogenic CaCO3-containing mineral phase. PLA composites containing a constant gentamicin sulfate loading of 5 wt% and 0, 10, 20, 30, or 40 wt% mineral phase were prepared and evaluated for gentamicin release in phosphate-buffered saline at pH 7.4 and 37 °C for 16 days. Release behavior was analyzed using mass and geometric normalization, multiple linear regression accounting for specimen thickness, and kinetic modeling of the early-stage and complete release profiles. Complementary FTIR, SEM/EDS, elemental, and water-uptake analyses were used to characterize the mineral phase, composite microstructure, and matrix interaction with the aqueous medium. Antibacterial activity of the hot-pressed matrices was additionally evaluated against Staphylococcus aureus and Escherichia coli. All compositions exhibited biphasic release, characterized by an initial rapid stage followed by slower release approaching a plateau. Increasing mineral-phase content was accompanied by a progressive increase in area-normalized gentamicin release (Q a ) and in the apparent Higuchi release constant (K H ), which increased from 0.650 ± 0.044 to 2.007 ± 0.195 µg·mm-2·h-1/2 between the 0 and 40 wt% formulations. The relationship between K H and mineral-phase content was strongly positive (R 2 = 0.9185, p < 0.0001), while the complete 0-16-day profiles were best described by an asymptotic first-order model. Importantly, mineral-phase content remained significantly and positively associated with mass-normalized gentamicin release after adjustment for specimen thickness, indicating that the composition-dependent effect could not be explained solely by geometric variability among the matrices. All investigated formulations retained pronounced antibacterial activity against both test microorganisms after hot pressing. These findings demonstrate that shell-derived mineral-phase content provides an effective compositional parameter for tuning gentamicin transport in compact PLA matrices without increasing antibiotic loading or chemically modifying the polymer. The combined release, kinetic, microstructural, and water-uptake data support a role of polymer-mineral organization and enhanced matrix-medium interaction in the observed composition-dependent release behavior while antibacterial functionality is retained after thermal processing.