Extracellular matrix-mimicking nanofibrous chitosan microspheres as cell micro-ark for tissue engineering

In the present study, extracellular matrix (ECM)-mimicking nanofibrous chitosan microspheres (NCM) were developed via thermal induction of chitosan molecular chain from alkaline/urea aqueous solution. The regeneration of NCM from chitosan was proved to be physical process. The morphology of NCM could be precisely controlled by adjusting the initial solution concentration and the reaction temperature. The NCM possessed desirable in vitro/vivo biocompatibility and biodegradability. The excellent cell adhesion capability of NCM facilitated the formation of large-sized 3D geometric constructs in vitro. The NCM promoted in vitro osteogenic differentiation of rat bone marrow stem cells (rMSCs). Finally, pre-differentiated rMSCs-NCM constructs obviously enhanced in vivo bone healing of rat calvarial defects. This work opened up a new avenue for the construction of chitosan microspheres with ECM-like nanofibrous structure, indicated the great potential of the NCM as micro-Noah's Ark for stem cells to anchor, proliferate, and pre-differentiate for tissue engineering. [Display omitted] •Chitosan microspheres with tunable ECM-mimicking nanofibers were successfully fabricated from alkaline/urea aqueous solution.•NCM demonstrated ideal biocompatibility, appropriate degradability, and excellent cell adhesion capability.•In vitro pre-differentiated cell-laden constructs obviously enhanced the in vivo bone healing of rat calvarial defects.•This work indicated the great potential of the NCM as cell micro-ark for tissue engineering.