FOUR-DIMENSIONAL BIOPRINTING AS A NEW ERA FOR TISSUE ENGINEERING AND REGENERATIVE MEDICINE

In the era of “big data,” coping with a society that is in constant development, the discovery of “new” scientific and technological knowledge must (i) progress at an incredibly fast pace, (ii) target a wide audience, and (iii) have a practical impact in the society by addressing relevant challenges. The health sciences are naturally a priority area of research, mostly because of the impact they have on augmenting human life expectancy and improving well-being, by developing advanced tailored approaches to address patient-specific needs. As an example, during the past decade, the wide amount of data gathered from the human genome project, along with the improved knowledge of genome regulatory mechanisms, brought about the development of synthetic biology and genomic editing techniques (Singh et al., 2017).

This massive advancement has been contributing not only to a better definition of disease mechanisms, but, importantly, also to the development of personalized therapeutic approaches. Indeed, the so-called “precision medicine” represents one of the main themes addressed by the European Commission health program, being featured in several distinct topics in the Horizon 2020 research and innovation program.1 In this context of incessant development of tools and improvements in the biomedical field, tissue engineering is playing a leading role as a multidisciplinary research branch. The ambition to cope with the complexity of human tissues, aimed at regenerating those hampered by diseases and age-related degeneration, has been the major goal of tissue engineering, which emerged in the 1980s, as a frontier scientific field with an enormous potential.

An overwhelming amount of tissue engineering strategies have been developed since then, aimed at regenerating bone, cartilage, skin, and many other tissues and organs, in the attempt to bridge structure (gross anatomy and histological architecture) with the corresponding function (physiology and cell biology), as a paramount challenge to be solved (Campana et al., 2014). On this regard, several efforts have been made worldwide to develop synthetic or semisynthetic constructs that could mimic native tissues. Most of the human native tissues are made of complex three-dimensional (3D) structures, presenting different shapes, architectures, specific cell types, and extracellular matrix compositions. Furthermore, these tissues are extremely plastic and not static, having unique functions suitable to dynamic changes in tissue conformations. Thus, the conventional approaches of creating static 3D structures are not sufficient for its usage in biomedicine and the achievement of 3D complex organ structures is far from being tangible (Woodfield et al., 2017). Implants for tissue engineering strongly depend on the (bio)materials and the manufacturing process. The conventional manufacturing processes do not present a properly control over pore size, geometry, and spatial distribution, not guaranteeing pore interconnectivity; which are key features for successful tissue regeneration (Hollister, 2005). Therefore, additive manufacturing (also known as 3D printing) techniques have gained an increased importance for the scientific community overlapping the referred drawbacks.