Use of manuka honey and oregano essential oil as antibacterial coatings for 3D-printed alginate/PVA/45S5 bioactive glass scaffolds

The treatment of infected bone defects remains a major clinical challenge due to the limitations of conventional systemic antibiotic therapies and the ability of bacteria to form resilient biofilms. In this context, scaffolds capable of delivering local antibacterial activity while supporting tissue regeneration represent a promising alternative. This study reports the fabrication of 3D-printed composite scaffolds composed of alginate, poly(vinyl alcohol) (PVA), and 45S5 bioactive glass, subsequently functionalized with gelatin (GEL) coatings incorporating manuka honey (MH) or oregano essential oil (OEO). Release studies showed that approximately 90% of MH and OEO were released within the first 7 days, suggesting a burst release mechanism. This translated into strong initial antibacterial activity of GEL + MH and GEL + OEO scaffolds against Staphylococcus aureus and Escherichia coli, although the effect decreased after 24 h. Based on the MIC values, OEO showed markedly higher antibacterial potential than MH against both bacterial strains, reinforcing its suitability as a potent natural agent. Cytocompatibility assays revealed that while MH and OEO in pure form displayed some cytotoxicity, their incorporation into the gelatin coating markedly reduced adverse effects, maintaining cell viability above the ISO 10993–5 threshold. These findings indicate that phytotherapeutic-functionalized gelatin coatings can provide effective short-term antibacterial protection without compromising cytocompatibility. Strategies to further optimize release profiles and prolong antibacterial activity are discussed. Overall, the developed scaffolds show strong potential for application in tissue engineering, particularly in infection-prone environments such as bone defect repair, with potential relevance to chronic wound healing applications. Graphical Abstract