Surface mechanical cues of biomaterial regulate macrophage polarization for facilitating critical bone defect repair

Surface properties of biomaterial could orchestrate the process of bone regeneration by mediating the response of immune cells. Herein, we fabricated biphasic calcium phosphate (BCP) scaffolds with different surface topography to investigate its critical bone defect repair performance and immunomodulation properties. We found that wBCP scaffold with whisker surface structure facilitate successful repair of critical sized bone defect and present superior osteoblastic and osteoclastic activity. The following in vitro and in vivo results showed that whisker surface structure induce the advanced switch of macrophage phenotype from M1 to M2 to generate a favorable immune microenvironment, which facilitate the osteogenic differentiation of BMSCs and ectopic bone formation. Transcriptomic analysis revealed that mechanical stress derived from surface whisker structure of wBCP scaffold may induce such advanced switch of macrophage phenotype by activating the transcription of Egr-1, which not only promote osteogenesis for bone formation but also activate osteoclastogenesis by up-regulated the transcription factors of Fos and Jun for scaffold reabsorption and eventually results in the successful repair of critical sized bone defect. This work provides a new insight into the design of immunomodulatory tissue engineering scaffold for critical sized bone defect repair.