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Moayad Alhariri,1 Majed A Majrashi,2 Ali H Bahkali,3 Faisal S Almajed,4 Ali O Azghani,5 Mohammad A Khiyami,2 Essam J Alyamani,2 Sameera M Aljohani,6 Majed A Halwani1 1Nanomedicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, 2National Centre for Biotechnology, Life Sciences and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), 3Botany and Microbiology Department, College of Science, King Saud University, 4Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 5Department of Biology, The University of Texas at Tyler, Tyler, TX, USA; 6College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia Abstract: We investigated the efficacy of liposomal gentamicin formulations of different surface charges against Pseudomonas aeruginosa and Klebsiella oxytoca. The liposomal gentamicin formulations were prepared by the dehydration–rehydration method, and their sizes and zeta potential were measured. Gentamicin encapsulation efficiency inside the liposomal formulations was determined by microbiologic assay, and stability of the formulations in biologic fluid was evaluated for a period of 48 h. The minimum inhibitory concentration and the minimum bactericidal concentration were determined, and the in vitro time kill studies of the free form of gentamicin and liposomal gentamicin formulations were performed. The activities of liposomal gentamicin in preventing and reducing biofilm-forming P. aeruginosa and K. oxytoca were compared to those of free antibiotic. The sizes of the liposomal formulations ranged from 625 to 806.6 nm in diameter, with the zeta potential ranging from &ndash

Large bone defects pose significant challenges in orthopaedic surgery, necessitating the exploration of innovative repair technologies beyond traditional treatments like autografts, allografts, and synthetic substitutes, each fraught with specific challenges. Tissue engineering and regenerative medicine have emerged as promising fields, employing bioactive materials, growth factors, and cellular components to emulate natural bone properties and functions. Notably, additive manufacturing techniques contribute to these advancements by customising 3D-printed scaffolds enhancing patient-specific treatments. Recent studies underscore the significant influence of immune responses in bone regeneration, an area still in its infancy. Particularly, the modulation of immune reactions through specialised biomaterials and the strategic delivery of anti-inflammatory agents like dexamethasone present a novel approach to support bone healing processes, avoiding the systemic side effects of traditional drug administration. In this thesis, novel inks were developed to sustain the release of dexamethasone from a 3D-printed scaffold to modulate the immune response and osteogenesis. Excipients with surfactant properties, including the poloxamers F127, F68, L31, sorbitan monooleate Span80, and sucrose acetate isobutyrate (SAIB), were added to PCL to test their ability to sustain drug release. All these inks were fabricated into scaffolds by using direct ink writing 3D printing technique. The fabricated scaffolds were then characterised by SEM, DSC, FTIR, and ToF-SIMS. Macrophages and mesenchymal stem cells (MSCs) were cocultured to investigate the effects of the controlled release of dexamethasone on the modulation of macrophage polarisation and osteogenic differentiation of MSCs. Notably, blending PCL with 40% wt/wt (SAIB) has improved dexamethasone-cyclodextrin dispersal and facilitated a sustained 35-day release dominated by first-ordered and Higuchi models. In this modified environme