Biofabrication of Conductive Materials for Cardiac Regeneration

Tese de mestrado, Engenharia Biomédica e Biofísica, 2023, Universidade de Lisboa, Faculdade de Ciências ; Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Heart donor shortage and cardiomyocyte poor self-renewal rate make it imperious to develop novel alternative therapies and approaches. To this end, Regenerative Medicine and Tissue Engineering (TE) have been playing an increasingly relevant role, and in particular 3D bioprinting techniques are a very promising solution as they allow to print human cells embedded in biocompatible materials in a controlled and precise fashion. However, a common problem found in cardiac cells bioprinting, is the lack of maturation of the printed or seeded cardiomyocytes. Moreover, nanomaterials with properties like electrical conductivity have been added to hydrogels to achieve properties suitable for cardiomyocyte culture. Hence, Alginate-Gelatin hydrogels containing either carbon nanotubes (CNTs), titanium carbide MXenes or no conductive nanomaterial were tested to be used as scaffolds for cell seeding and bioinks for bioprinting. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CM) were seeded in 3 different hydrogel sheets (control - without particles -, with CNTs and with MXenes) and encapsulated in 3 bioinks with the same composition, for further extrusion bioprinting. Cell viability and metabolism were assessed. Primary tests regarding the conductivity and other relevant physical properties were conducted prior to cell culture. Findings suggested that both CNTs and MXenes have a positive effect on hiPSC-CMs metabolism without compromising cell viability. For seeded constructs, both conductive nanomaterials are thought to improve the maturation of hiPSC-CMs as after 6 days of culture there were clusters of cells displaying a mature phenotype. Yet, bioprinted hiPSC-CMs did not exhibit signs of maturity, as they did not spread along the hydrogel matrix and maintained a round shape, which is an indicator of low expression of contractile ...