Antibiotic-Loaded Calcium Crosslinked Alginate Wound Dressings Fabricated via Pressurized Gas eXpanded Liquids Technology in Combination with Supercritical Adsorptive Precipitation for Treating Methicillin-Resistant Staphylococcus Infections

This study presents a solvent-free, scalable wound-dressing platform that couples Pressurized Gas eXpanded Liquids Technology (PGXTEC) with supercritical CO2 adsorptive precipitation to locally deliver poorly water-soluble antibiotics from highly porous, calcium-crosslinked alginate hydrogel disks. PGXTEC processing generated macroporous alginate aerogel-like scaffolds that were simultaneously crosslinked (PGXTEC-CA), then mechanically compacted into thin porous films and punched into standardized disks while retaining very high BET surface area (~143 m2/g after compression), enabling drug precipitation at the pore interface. The crosslinked disks exhibited rapid wetting/absorption in multiple clinically relevant fluids and formed stable hydrogels during swelling in Ca2+-supplemented buffer with large equilibrium swelling ratios (~12) and indentation-derived compressive moduli decreasing from ~584 kPa (dry) to ~159 kPa after hydration—still sufficient for handling. Using supercritical adsorptive precipitation, the authors loaded fusidic acid (FA; ~5.1 µg per disk) and tigecycline (TIG; ~155 µg per disk), achieving rapid initial release with plateauing by ~8 h and different dominant release mechanisms (dissolution-limited for FA vs diffusion-dominated for TIG). Both drug-loaded disks produced clear in vitro zones of inhibition against MRSA. In a full-thickness MRSA-infected murine wound model (48 h), FA-loaded disks suppressed bacterial growth and reduced dissemination to spleen, while TIG-loaded disks sterilized wounds and largely prevented systemic spread—suggesting substantial dose-sparing and enhanced local bioavailability, including conversion of TIG’s typical bacteriostatic behavior to bactericidal performance when delivered locally from the porous scaffold.