Fabrication and Characterization of Multi-scale Biomaterial Models for Bacteriotherapy

In this thesis, we aimed at designing and fabricating multi-scale probiotic delivery systems for bacteriotherapy. Two distinct target infectious diseases, namely ulcers and chronic middle ear otitis, were considered and addressed with specific bacteriotherapeutic vehicles. Sodium alginate was selected as the primary material for all the delivery systems, and a careful selection of the best type of alginate was carried out for each application. For the treatment of chronic otitis, 0D particles and 2D fibrous meshes were bio-fabricated exploiting the electrospinning technique. Electrosprayed particles were produced with high molecular weight, low M/G ratio sodium alginate, while multiple fabrication strategies were explored to electrospin alginate fibers. First, a co-solvent approach was investigated to produce pure alginate fibers, whereas the second fabrication method involved the use of PEO as a co-polymer. 3D patches to treat chronic ulcers were bio-printed using an extrusion-based 3D printer. Alginate-based bio-inks were prepared and tested to identify the best performing formulation and printing conditions. All the bio-fabricated materials were characterized in terms of morphology, rheology, swelling, degradation and biological properties. Model commercial probiotics were then selected and loaded into the delivery systems, and the processing conditions were re-evaluated and properly adjusted to achieve the formation of bacteriotherapy devices with the desired characteristics. Further studies were conducted with the 3D printed patches to assess the viability of encapsulated bacteria and the potential therapeutic action against wound-specific pathogens