Engineered Microchannel Scaffolds with Instructive Niches Reinforce Endogenous Bone Regeneration by Regulating Csf-1/Csf-1r Pathway.

Structural and physiological cues provide guidance for the directional migration and spatial organization of endogenous cells. Here, we developed a microchannel scaffold with instructive niches using a circumferential freeze-casting technique with an alkaline salting-out strategy. Thereinto, polydopamine-coated nano-hydroxyapatite (nHAp@PDA) was employed as a functional inorganic linker to participate in the entanglement and crystallization of chitosan molecules. This scaffold orchestrates the advantage of an oriented porous structure for rapid cell infiltration and satisfactory immunomodulatory capacity to promote stem cell recruitment, retention, and subsequent osteogenic differentiation. Transcriptomic analysis as well as its in vitro and in vivo verification demonstrated that essential CSF-1 factor was induced by this scaffold, and effectively bound to the target receptor of CSF-1R on the macrophage surface to activate the M2 phenotype, achieving substantial endogenous bone regeneration. This strategy provides a simple and efficient approach for engineering inducible bone regenerative biomaterials. This article is protected by copyright. All rights reserved.