For many years scientists have been trying to expand hematopoietic stem cells (HSCs) in vitro due to their application in the cure of leukemia and other hematological diseases. As HSCs continuously self-renew in their natural environment, current approaches try to mimic their so-called niche. These artificial niches should not only imitate the chemical and biological composition of the natural archetype but also its physical properties, such as material rigidity or dimensionality. Our group has developed biomimetic macroporous and functionalized 3D scaffolds to cultivate HSCs in coculture with mesenchymal stem cells (MSCs). The macroporous hydrogel imitates the spongy architecture of the trabecular bone marrow, where HSCs can naturally be found and where they reside often in close proximity to MSCs, which support the HSCs in self-renewal. In 3D cultures MSCs behave differently compared to conventional 2D cultures, particularly in their ability to support HSC proliferation. To investigate this effect we want to gain a deep understanding of the interaction between HSCs and MSCs in our system on the transcriptomic level. Therefore, degradability needs to be introduced into our 3D scaffold to quickly regain MSCs and HSCs from the system without affecting the transcriptome.