(84d) Modular Design of Microfluidic Hydrogel Scaffold for Bone Marrow Bioengineering

There is a critical need to develop micro-physiological human bone marrow tissue models to facilitate fundamental understanding of bone marrow biology and to improve the predictive power of bone marrow toxicity testing.  Various scaffolds and microfluidic designs have been developed to simulate complex and dynamic bone marrow microenvironment; however, these platforms fall short of capturing full-spectrum anatomical, physical and hydrodynamical features of the bone marrow niche in a single platform that is essential for mechanistical studies.  Here we introduce a modular design of microfluidic hydrogel scaffold that systematically increases the bone marrow tissue complexity combining a marrow-mimicking hydrogel scaffold with a microfluidic device.  Hydrogel scaffolds prepared using colloidal crystals as a template closely emulated the physical and anatomical features of bone marrow to scale.  The hydrogel scaffold was then integrated into a PDMS-based fluidic chamber by taking advantage of dramatic and reversible volume change (~78%) between a hydrated and a dehydrated state.  The relative flow rate of a scaffold-chamber was ~90% of an empty chamber and its perfusion profile recapitulated both vascular convection and tissue diffusion in the bone marrow sinusoids because of the nature of the biomaterial design.  Primary human bone marrow stromal cells were effectively seeded into a hydrogel scaffold in a chip and maintained high viability under perfusion culture condition.  Finally as a proof of concept we demonstrated the dynamic interaction between floating human Nalm-6 leukemic cells and adhered human bone marrow stromal cells in the scaffold-chamber.  We envision that the presented modular design of marrow-mimicking microfluidic scaffolds would provide a new preclinical testing dimension for various bone marrow related in vitro studies with advanced analytical and predictive power.