(267h) Biomimetic Scaffolds for in vitro Bone Marrow Tissue Engineering

In vitro human bone marrow tissue replicas represent unique opportunity for studying bone marrow biology and realizing ex vivo expansion of hematopoietic stem cells. Major cellular and molecular components constituting bone marrow microenvironment have been identified, but recapitulating full-range bone marrow functions in vitro remains an elusive task. This is in part due to the lack of relevant culture platforms that reflect bone marrow-like extracellular milieu. From a mechanical aspect, marrow is the softest tissue that is formed inside of the hardest tissue in the body, bone. We hypothesized that extreme contrast of biophysical properties in a microscale porous geometry could be critical in delineating stromal cell function and subsequently supporting hematopoiesis. To test this hypothesis, we have developed a glass-bead and methylcellulose hybridized 3D porous hydrogel scaffold that reflects both soft and hard part of bone marrow in a controlled and analytical manner. The hybrid scaffold design enables to study the role of biophysical, biochemical, and structural cues in directing primary human bone marrow derived stromal cells behavior. Integration of soft and hard materials in a single 3D platform would be an effective strategy to create functional in vitro bone marrow tissue models. We further increased the model complexity by introducing a well-plate based 3D bioreactor and a hypoxic chamber that provide marrow-like mechanical and oxygen milieu. We envision that established ex vivo bone marrow tissue models can advance various aspects of bone marrow related studies serving as an enabling tool.