From cell to society: Bioengineering auricular cartilage for ear reconstruction

Abstract

Regenerative medicine strategies have the potential to substitute surgical techniques for reconstruction of auricular malformations in the future. It is possible to generate new tissues in the laboratory, using a combination of cells, biomaterials and bioactive molecules. Further, bioprinting technologies allow precise placement of these ingredients in a three-dimensional (3D) space. Complex geometries can be generated this way, from which specific tissues or organs can develop. This thesis focuses on several challenges in bioengineering cartilage for ear reconstruction: choice of cell type, stability of fabricated ear constructs, and ethical considerations. First, novel cartilage progenitor cells that have the ability to generate a sufficient number of cells required for the creation of a complete auricle from just a small biopsy, were identified in animal and human ear cartilage. These cells were not adversely affected by the bioprinting process and produced cartilaginous tissue in small 3D hydrogel constructs. Subsequently, bioprinting techniques were used to fabricate full-size ear-shaped constructs using progenitor cells in a hydrogel reinforced with polymer fibers. Advanced imaging techniques demonstrated that the shape and size of the constructs were maintained during the culture period and that abundant new cartilage had formed. This combination of strategies offers an interesting perspective for auricular reconstruction. Moreover, this thesis also addresses the importance of patient stakeholder involvement in the research process and its translation into society, and the realistic presentation of scientific results to the public.