Stage-Adaptive Polymeric Platforms: Design of an Alginate/CMC Hydrogel Co-Loaded With Silver Nanoparticles and α-Pinene-Rich Essential Oil for Wound Regeneration.

Managing infected wounds requires a delicate balance between rapid antimicrobial activity and continued tissue repair. To meet this challenge, we developed a porous carboxymethyl cellulose (CMC)/alginate hydrogel loaded with Silver nanoparticles and a Pistacia atlantica essential oil rich in α-pinene. The hydrogel displayed remarkable swelling (up to 6362% over 72 h) and changed the essential oil release from a rapid, volatile burst to a sustained, controlled profile (73% steady release over 96 h). In vitro tests revealed potent antibacterial activity against Staphylococcus aureus (MIC = 650 μg/mL), significant antioxidant properties, and excellent cytocompatibility. Importantly, in vivo studies in mice demonstrated a stage-adaptive healing mechanism. Silver nanoparticles allowed rapid early infection control (47.4% wound closure by Day 4). Subsequently, the sustained release of the essential oil promoted robust tissue regeneration during the proliferative phase (82.6% closure by Day 7), driven by an enhanced TAC-mediated antioxidant defense, reduced MDA levels, and accelerated hydroxyproline-associated collagen synthesis. By Day 13, re-epithelialization was near-complete (93.6%), matching commercial controls. Ultimately, this synergistic integration of plant-derived bioactives and metal antimicrobials presents a highly effective, stage-specific platform for accelerated wound healing.