A vascularized bone-on-a-chip model development via exploring mechanical stimulation for evaluation of fracture healing therapeutics

Bone is the major connective tissue maintaining the structural integrity of the human body. However, fracture and many skeletal degenerative diseases can compromise this function. Thus, therapeutics related to bone degeneration are of significant research interest and require good in vitro models for such therapeutic evaluation. Bone is a highly vascularized tissue and incorporation of this feature is significantly important for mimicking the osteogenic microenvironment. In the current study, we developed a vascularized flat bone model via simultaneous mechanical actuation of mechanical strain and fluid shear. The mechanical strain was achieved by static magnetic field actuation of a magnetic nanocomposite scaffold. The fluid shear was generated by developing a micropattern on the magnetic nanocomposite via replica molding and laser-based microfabrication. From the live cell imaging window of the microdevice, both bone and vasculature like cellular morphology was observed. The SEM study showed thick ECM deposition in the dynamic culture. In the PCR study, both osteogenic (Col-1, osteocalcin) and angiogenic phenotypes (PECAM) were observed in the dynamic culture scaffolds while chondrogenic marker (Col-2) was downregulated.