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Liver is one of the most important and complex organs in the human body, being characterized by a sophisticated microarchitecture and responsible for key physiological functions. Despite its remarkable ability to regenerate, acute liver failure and chronic liver diseases are major causes of morbidity and mortality worldwide. Therefore, understanding the molecular mechanisms underlying such liver disorders is critical for the successful development of novel therapeutics. In this frame, preclinical animal models have been portrayed as the most commonly used tool to address such issues. However, due to significant species differences in liver architecture, regenerative capacity, disease progression, inflammatory markers, metabolism rates, and drug response, animal models cannot fully recapitulate the complexity of human liver metabolism. As a result, translational research to model human liver diseases and drug screening platforms may yield limited results, leading to failure scenarios. To overcome this impasse, over the last decade, 3D human liver in vitromodels have been proposed as an alternative to pre-clinical animal models. These systems have been successfully employed for the investigation of the etiology and dynamics of liver diseases, for drug screening, and – more recently – to design patient-tailored therapies, resulting in potentially higher efficacy and reduced costs compared to other methods. Here, we review the most recent advances in this rapidly evolving field with particular attention to organoid cultures, liver-on-a-chip platforms, and engineered scaffold-based approaches.

The functional capabilities of skeletal muscle are strongly correlated with its well-arranged microstructure, consisting of parallelly aligned myotubes. In case of extensive muscle loss, the endogenous regenerative capacity is hindered by scar tissue formation, which compromises the native muscle structure, ultimately leading to severe functional impairment. To address such an issue, skeletal muscle tissue engineering (SMTE) attempts to fabricate in vitrobioartificial muscle tissue constructs to assist and accelerate the regeneration process. Due to its dynamic nature, SMTE strategies must employ suitable biomaterials (combined with muscle progenitors) and proper 3D architectures. In light of this, 3D fiber-based strategies are gaining increasing interest for the generation of hydrogel microfibers as advanced skeletal muscle constructs. Indeed, hydrogels possess exceptional biomimetic properties, while the fiber-shaped morphology allows for the creation of geometrical cues to guarantee proper myoblast alignment. In this review, we summarize commonly used hydrogels in SMTE and their main properties, and we discuss the first efforts to engineer hydrogels to guide myoblast anisotropic orientation. Then, we focus on presenting the main hydrogel fiber-based techniques for SMTE, including molding, electrospinning, 3D bioprinting, extrusion, and microfluidic spinning. Furthermore, we describe the effect of external stimulation (i.e., mechanical and electrical) on such constructs and the application of hydrogel fiber-based methods on recapitulating complex skeletal muscle tissue interfaces. Finally, we discuss the future developments in the application of hydrogel microfibers for SMTE.