Bone marrow is a highly complex tissue, in which the regenerative systems of blood and bone are closely interlaced. Hematopoietic stem cells (HSCs) are at the root of blood formation and give rise to all different types of blood cells including erythrocytes and immune cells. Nowadays, HSCs are the only stem cells routinely applied in the clinics to treat patients that suffer from hematological disorder such as leukemia. Therefore, being able to manipulate or multiply HSCs in vitro is highly desirable from a clinical point of view.
In vivo HSCs are tightly controlled by their local microenvironment – their so-called stem cell niche in the bone marrow. In this niche HSCs receive all the signals that they need to maintain their stem cell properties (i.e. the abilities to differentiate and to self-renew). These signals include not only biological signals such as growth-factors, cell-cell contacts or cell-matrix interactions but also physical stimuli such as matrix stiffness, nanopatterning or the three-dimensional architecture of the environment. During the last years, we could show that all these parameters are able influence HSC behavior. Using conventional approaches to create 3D cell culture scaffolds, we found that an appropriate 3D architecture of the environment is particularly crucial in the development of in vitro systems that allow targeted HSC proliferation and differentiation. Such conventional approaches, however, do not allow a full biomimicry of the bone marrow. Additive manufacturing might be the key to achieve this goal.
Which are the requirements for a perfect bone marrow analog? How could 3D printing – including printing of stiff inorganic material, soft matrices and cells - help of fulfill these requirements? These questions will be addressed in order to evaluate, how bioprinting could help us to do another step towards a synthetic bone marrow analog that allows the in vitro multiplication of HSCs.