Modulating Macrophage Polarization With <scp>3D</scp> ‐Printed Porous Scaffolds Promotes Bone Regeneration: An In Vivo Study

ABSTRACT In recent years, the biological scaffold materials used for craniomaxillofacial defects have developed rapidly, but the effect of scaffold surface aperture on cell adhesion, osteogenesis‐related cytokine expression and even bone tissue repair is still unclear. Here, the Type I collagen payload is combined to form a biological scaffold based on the high‐precision 3D‐printed PCL porous scaffold prepared in the previous experiment. In vivo experiments in rat skull defect models, it was found that the P500 group could promote the differentiation of macrophages to M2 type, reduce the expression of pro‐inflammatory cytokines, and increase the expression of anti‐inflammatory cytokines in the early stage of osteogenesis (1 week). In the middle and late stages of osteogenesis, the P500 scaffold group had encouraging performance in Micro‐CT three‐dimensional reconstruction and ALP and OCN immunohistochemical staining, and the large aperture scaffold effectively promoted the microenvironment of M2 polarized macrophages in the early bone defect, avoided excessive inflammatory response, and further promoted bone repair. This work further enhances the confidence of the results at the previous in vitro cell level at the animal level. In conclusion, our results suggest that increasing the surface pore size of biological scaffolds may be an effective way to promote bone repair from the perspective of early immunomodulation and late induction of osteogenesis in a certain range.