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Digital archive of theses discussed at the University of Pisa


Thesis etd-04022012-094717

Thesis type
Tesi di dottorato di ricerca
Thesis title
Indirect microfabrication of biomimetic materials for locomotor tissues regeneration
Academic discipline
Course of study
tutor Prof. Cerulli, Giuliano
tutor Prof. Vozzi, Giovanni
  • agarose
  • DMSO
  • indirect microfabrication
  • inkjet
  • mold
  • paraffin wax
  • tissue engineering
Graduation session start date
Tissue Engineering is a new field of the scientific research with a final aim to develop techniques for regeneration, repair, maintenance and growth of tissues or organs to overcome the limitations intrinsic to current therapeutic strategies. A fundamental element of this approach is the scaffold. The scaffold is a 2D and 3D structure, made with natural or synthetic material, that emulates the extracellular matrix, that is it offers mechanical, topological, biochemical and chemical stimuli to promote cellular organization, growth and differentiation to create a tissue with adequate functional and morphological characteristic. Scaffolds are therefore characterized by peculiar features (e.g. porosity, mechanical properties) determined by the material and by the manufacture process.
Nowadays, the additive Rapid Prototyping (RP) techniques are the best approach to realize complex structures, because overcome all the problem of conventional (subtractive) techniques.
Despite the high potential, RP techniques are not always compatible with all materials. In particular, hydrogels, an elective class of biomaterial for scaffolds realization because the lot of features in common with the extracellular matrix, results very difficult to be processed. To overcome these limitations and take advantage of all benefits of rapid prototyping, indirect rapid prototyping (iRP) was developed, that is the realization of scaffold or other structures starting from sacrificial molds realized by RP. The iRP offers the benefits to fabricate composite scaffold realized with different materials, with less waste and high fidelity in the realization of the designed structure. One of the critical aspect of this class of realization process is the extraction of the final object from the mold. A possible solution, proposed in this research, is to realize the mold with low melting point materials, dissolving the mold at the end of the process without damaging the scaffold. Moving in this direction, the attention of this research is focused on two classes of materials, low melting point waxes and agarose.
Two alternative RP techniques have been evaluated: new modules of the PAM^2, a continuous flow system, and a inkjet-based device have been designed and realized to test the feasibility of this approach. In addiction, an alternative approach to fabricate agarose microstructure, by exploiting the different agarose gelling ability in DMSO and water, has been proposed.
In a future perspective, casting of the desired material, which may include also cells, should be performed directly in the surgery room using an anatomical shaped mold designed on the patient needs. Following this approach, two plugins for bioimages de-noising and segmentation, based on the ITK library, have been implemented for the OsiriX software.
To further test the versatility of the two microfabrication devices, other applications have been explored, such as the realization of microfluidic circuits using PAM^2 or printing carbon nanotubes suspension for polymeric actuators.