Strontium-Doped Marine Collagen Membranes Promote Osteogenesis by Inducing M2 Macrophage Polarization.

Abstract

Background: The design of bone biomaterials has shifted from promoting bone differentiation to "immune osteogenic coupling". Macrophages play a key role in immune regulation, with their polarization state critically shaping the bone tissue immune microenvironment. While collagen membranes, as classic guided bone regeneration (GBR) barriers, offer excellent biocompatibility and degradability, they lack inherent bone induction and immune regulation capabilities, limiting their use in complex bone defect repair.

Methods: In this study, we proposed a novel optimization strategy utilizing phase-transited lysozymes (PTL) incorporating strontium (Sr²⁺) into marine collagen membranes (Sr-PTL-MCM) and investigate their osteoimmunomodulatory effect through a series of experiments.

Results: Sr-PTL-MCM were successfully synthesized via the PTL technique and continuously released Sr²⁺ ions over 7 days. Sr-PTL-MCM can effectively induce macrophage polarization from the M0 to M2 phenotype, suppresses the secretion of inflammatory cytokines, thereby enhancing mBMSCs osteogenic differentiation. RNA-sequence analysis reveals that Sr-PTL-MCM promotes M2 polarization via JAK-STAT and MAPK signaling pathways. In vivo experiments confirm its ability to create a favorable bone immune microenvironment, promoting bone growth and regeneration.

Conclusion: In conclusion, incorporating Sr ions into collagen via PTL technique represents a promising approach for developing collagen membranes with immunomodulatory characteristics, thereby providing a novel and effective strategy for bone defect repair.