Sea Urchin‐Inspired Immuno‐Instructive Ionic Flow Drives MSCs‐Macrophage Communication to Promote Bone Regeneration

Abstract

ABSTRACT Bone tissue regeneration is a complex physiological process dependent on the spatiotemporal coordination of immune cells and stem cells. Conventional research primarily elucidates the mechanism through which materials facilitate bone formation by initially modulating macrophages and subsequently encouraging the osteogenic differentiation of stem cells, while largely overlooking the proactive regulatory influence of stem cells on immune cells. Consequently, investigating the capacity of materials to concurrently attract stem cells and modulate innate immune infiltration, while establishing a tissue microenvironment response mechanism, holds substantial importance for the development of next‐generation tissue regeneration materials. This study introduces a sea urchin‐inspired immune instructional ionic flux (SUIF) platform, characterized by a radial mesoporous structure that employs B─O bond dissociation/dissolution rates and Sr 2 + slow‐release mechanisms to create a “fast‐slow biphasic” ionic flow release, thereby establishing a dynamic alkaline ionic flow microenvironment. Within this microenvironment, 5B5Sr‐SUIF recruits MSCs and stimulates MSCs to enhance the expression of miR‐466m‐5p, thereby obstructing the nuclear translocation of NF‐κB in macrophages. This facilitates immunological regulatory communication between mesenchymal stem cells and macrophages, offering novel material design principles and molecular mechanism support for the exact regeneration of complicated bone deformities.