Xu Hao, Li Xin, Wang Wenxue, Zhen Li, Zhao Baodong
Department of Oral Implantology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao, 266035, Shandong, China.
School of Stomatology of Qingdao University, Qingdao, 266003, China.
Tissue Eng Regen Med. 2025 Jul 14. doi: 10.1007/s13770-025-00732-x.
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.
In this study, we proposed a novel optimization strategy utilizing phase-transited lysozymes (PTL) incorporating strontium (Sr) into marine collagen membranes (Sr-PTL-MCM) and investigate their osteoimmunomodulatory effect through a series of experiments.
Sr-PTL-MCM were successfully synthesized via the PTL technique and continuously released Sr 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.
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.
骨生物材料的设计已从促进骨分化转向“免疫成骨偶联”。巨噬细胞在免疫调节中起关键作用，其极化状态对骨组织免疫微环境起着至关重要的塑造作用。虽然胶原膜作为经典的引导骨再生（GBR）屏障，具有优异的生物相容性和可降解性，但它们缺乏内在的骨诱导和免疫调节能力，限制了其在复杂骨缺损修复中的应用。
在本研究中，我们提出了一种新的优化策略，即利用将锶（Sr）掺入海洋胶原膜中的相转变溶菌酶（PTL）（Sr-PTL-MCM），并通过一系列实验研究其骨免疫调节作用。
通过PTL技术成功合成了Sr-PTL-MCM，并在7天内持续释放Sr离子。Sr-PTL-MCM能有效诱导巨噬细胞从M0表型极化为M2表型，抑制炎性细胞因子的分泌，从而增强小鼠骨髓间充质干细胞（mBMSCs）的成骨分化。RNA序列分析表明，Sr-PTL-MCM通过JAK-STAT和MAPK信号通路促进M2极化。体内实验证实了其创造有利骨免疫微环境、促进骨生长和再生的能力。
总之，通过PTL技术将Sr离子掺入胶原蛋白中是开发具有免疫调节特性的胶原膜的一种有前途的方法，从而为骨缺损修复提供了一种新颖有效的策略。
