The field of tissue engineering and regenerative medicine has made numerous advances in recent years in the arena of fabricating multifunctional, three-dimensional (3D) tissue constructs. to proliferate, differentiate, and migrate. The advances of bioprinting stem cells and directing cell fate have the potential to provide feasible and translatable approach to creating complex tissues and organs. This review will examine the methods through which bioprinted stem cells are differentiated into desired cell lineages through biochemical, biological, and biomechanical techniques. Graphical Abstract 1.?INTRODUCTION The field of tissue engineering and regenerative medicine has made expeditious advancements in creating multifunctional, three-dimensional (3D) tissue constructs.1,2 This is largely attributed to the progress in numerous bioprinting approaches.1-4 The ability to bioprint a singular construct that has the potential to mature into a functional tissue would facilitate an expansion of experimental designs, as well as a more rapid translation of a bioprinted tissue or organ to living models.5,6 There are expansive options in bioprinting technologies that have become more refined and specialized over the years. Approaches to cell delivery vary from multicellular, cell aggregate, and droplet-based or single cell bioprinting methodologies. Multicellular approaches include jetting-based, microextrusion-based, laser-assisted, and stereolithography-based techniques. Notably, the use of stem cells in bioprinting has addressed many limitations in cell source, expansion, and development of bioengineered tissue constructs. To this end, the use of stem cells in bioprinting offers a feasible option. The bioprinting of cells with an ability to mature to differing functional phenotypes presents an abundance of applications in lab-based models and clinical treatments. Stem cells present an opportunity in that they have the ability to replicate rapidly, as well as differentiation to a functional cell type based on various cues in the culture environment. Stem Etofenamate cells present varying potencies and capabilities toward differentiation, which inform their potential uses in tissue constructs.7-9 Potency is an important consideration in selecting the type of stem cells to employ in bioprinted constructs. Cell sources such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells have differing differentiation potentials, and thus, can be utilized for different tissue applications or purposes. Multiple bioprinting approaches have been paired with stem cell differentiation techniques to successfully generate target tissue constructs. One major consideration in the development of constructs comprised of bioprinted stem cells is the future applications or uses of the fabricated tissue construct. While some uses may be for disease modeling or pharmaceutical research in settings, other uses may be targeted to clinical and therapeutic applications for patients. The desired utilization of the construct may dictate the bioprinting technologies, stem cell type or cell source, and what factors from the microenvironment are optimized or manipulated. Etofenamate One of the most essential elements in the improvement of the field may be the optimization from the mobile microenvironment. To be able to fabricate constructs that are of help in replicating circumstances in laboratory configurations, selecting the optimal circumstances is essential. Fabricating a microenvironment that mimics physiological configurations, including incorporating elements in to the printing procedure, aswell as presenting them in to the culture from the build post-printing determines the achievement of final results. These add the inclusion of biochemical cues, such as for example small molecules, development elements, peptides, exosomes, little RNAs, bioink additives, and various other influential factors. Likewise, the introduction of a scaffold that reflects the organic extracellular matrix (ECM) is essential. Essential will be the mechanised properties of biomaterials that facilitate proliferation Similarly, differentiation, and maturation of stem cells. Included in these are, but aren’t limited by, the mimicry of an operating ECM, the topography Etofenamate from the bioprinted scaffold or build, as well as the elasticity and stiffness of bioinks and other components. This review shall investigate these areas of optimizing a microenvironment for bioprinted stem cells, aswell as examine latest literature and research Klf2 pertaining to developments in numerous tissues and organ systems in the last five years. Contemporary analysis in stem cell bioprinting provides produced novel Etofenamate strategies in bone tissue, cartilage, heart, liver organ, muscular, neural, and epidermis tissues systems. As each organ and tissues requires distinctive circumstances to induce the development, migration, and fate of cells, we will examine how very similar techniques and elements have been useful to develop disparate microenvironments to foster the development of these tissues types. The advances of bioprinting stem cells and directing cell fate possess the to supply translatable and feasible.