Crafting Tissue Complexity
Authors:   , Núñez Bernal Paulina 
Published: January 2024

The global rise in life expectancy is accompanied by an increasing prevalence of chronic diseases, posing economic burdens and impacting patients' well-being. This surge in disease incidence challenges the drug discovery pipeline, calling for the adaptation of its rules and regulations to reduce the ever-increasing failure rates of new drugs. The staggering growth of the pharmaceutical industry in the last decades, and the high expenditure required to bring new drugs to the market is set to become an unsustainable issue in the coming years. Recently, far more attention has been focused on the preclinical phase of the pipeline, where drug evaluation culminates in animal testing, the current gold standard to ensure drug safety and efficacy before human trials. A consensus on the need for more complex and predictive human disease models has emerged and become a priority for scientists and policy makers in the past decade.

Biofabrication, an emerging technology-driven field, has gained prominence in biomedical research for developing advanced in vitro models. Biofabrication is “the automated generation of biologically functional products with structural organization from living cells, bioactive molecules, biomaterials, cell aggregates such as micro-tissues, or hybrid cell-material constructs, through Bioprinting or Bioassembly and subsequent tissue maturation processes”. The last decades have seen the rapid development new bioprinting modalities, opening the door to the development of architecturally complex in vitro platforms where multi-cellular and multi-material structures can be more easily created. Considering the need for more complex preclinical models to bridge the translational gap between 2D in vitro models, animal testing and clinical trials, the overarching aim of this thesis was “to develop new biofabrication approaches, encompassing 3D bioprinting technologies, powerful biological building blocks, and smart biomaterials, that facilitate the development of advanced human in vitro models with native tissue-like functionality”.

This research has introduced significant advancements within the field of biofabrication for the generation of human in vitro models. Through a comprehensive exploration that tackled challenges related to fundamental bioprinting principles, the biological intricacies, and the biochemical and material property requirements of bioprinted structures to better recapitulate native tissues, the developments described here have expanded the toolkit of biofabrication approaches. By introducing novel technologies, like the pioneering, layerless volumetric bioprinting strategy, and synergizing new and existing printing approaches to harness their unique advantages, this thesis showcases a variety of functional bioprinted tissue models that enable the study of biological processes in vitro. The thorough exploration of volumetric bioprinting, distinguished by its scalability, unparalleled design freedom, compatibility with advanced biological tools, and a growing library of smart materials, charts new paths toward the creation of clinically-relevant testing platforms. The bioprinted, tissue-specific in vitro models presented here offer enhanced physiological accuracy and predictability and hold the potential to incorporate patient-specific elements for personalized medicine. The toolkit developed in here represents a significant stride in bridging the translational gap of tissue-engineered in vitro models, particularly in the context of preclinical testing. All in all, the evolving landscape of biofabricated in vitro models holds promise for innovative approaches in the future.