Patient-Specific Dual-Function 3D-Printed Gels for Antimicrobial and Analgesic Management of Alveolar Osteitis

Alveolar osteitis (AO), or dry socket, is a painful postoperative complication caused by the premature loss of the blood clot from the extraction site. Current treatments rely on irrigation and temporary dressings, however these approaches offer limited therapeutic benefits and often require repeated interventions. This work describes a customizable, dual-function biomaterials platform based on 3D-printed gelatin gels incorporating the antimicrobial quaternary ammonium compound, benzyldimethyldodecylammonium (BDMDAC), and the analgesic lidocaine enabling sustained infection control and localized pain management. 3D-printed gels were optimized for printability, mechanical stability, and controlled drug release, and their physicochemical properties were characterized through swelling, degradation, and release studies. Both hydrated and freeze-dried gels were evaluated to assess how architecture influences transport behavior and therapeutic performance. Antimicrobial efficacy was evaluated against clinically relevant oral pathogens, including Porphyromonas gingivalis, Enterococcus faecalis, and Streptococcus mutans which are key pathogens associated with oral infections. Cytocompatibility and inflammatory responses were assessed using human gingival fibroblasts (HGF-1s) as well as Interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) expression. The 3D-printed gels sustained antimicrobial activity, achieving complete planktonic pathogen eradication and biofilm inhibition within 24 h, independent of lidocaine incorporation. Analysis of pro-inflammatory cytokine markers showed a minimal response in most gel formulations, with a slight increase at high lidocaine concentrations (30 mg/mL), whereas freeze-dried gels produced a more pronounced early inflammatory response at this concentration. Finally, 3D printed anatomical patient-specific molar-shaped gels preserved antimicrobial efficacy comapred with grid-printed controls, confirming that therapeutic performance is maintained across complex geometries. Overall, these results demonstrate that on-demand fabrication of patient specific, antimicrobial, and analgesic 3D printed gels has the potential to be used for localized management of AO.