Wang Shuze, Cao Lei, Huang Caihao, Wang Junyi, Liu Jialin, Wang Yeyuan, Wang Qiang, Zhou Qing, Zhang Xing, Zhang Dan
School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China.
Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, 110001, China.
Bioact Mater. 2025 Jul 1;52:829-844. doi: 10.1016/j.bioactmat.2025.06.053. eCollection 2025 Oct.
The repair of alveolar bone defects continues to pose a significant challenge within the field of stomatology. As the primary implant material utilized in clinical treatment, the mechanisms by which calcium phosphate-based materials promote bone formation necessitate further in-depth exploration. Single-cell RNA sequencing was employed to characterize the immune microenvironment surrounding hydroxyapatite (HA)-mediated alveolar bone regeneration, confirming the macrophage-dependent enhancement of regenerative outcomes. Based on this finding, amorphous calcium zinc phosphate (ACZP) nanoparticles were developed as immunomodulatory nanomaterials. ACZP can accelerate bone regeneration via anti-inflammatory phenotype polarization, specifically by inhibiting endoplasmic reticulum-mitochondria coupling, reducing pathological Ca transfer, and shifting macrophage metabolism from glycolysis to oxidative phosphorylation (OXPHOS), thereby enhancing bioenergetics. Our results demonstrated that ACZP can inhibit the IP3R/MCU pathway in macrophages, restoring their anti-inflammatory capabilities and ultimately achieving significant effects in the alveolar bone defects of New Zealand white rabbits. Twelve weeks post-surgery, the defects in the ACZP group were filled with nearly 70 % newly formed bone tissue. This study elucidated the immunomodulatory role of ACZP materials in the dynamic process of alveolar bone healing, providing novel insights and methodologies for the design of materials in the fields of tissue engineering and regenerative medicine.
牙槽骨缺损的修复在口腔医学领域仍然是一项重大挑战。作为临床治疗中使用的主要植入材料，磷酸钙基材料促进骨形成的机制需要进一步深入探索。采用单细胞RNA测序来表征羟基磷灰石（HA）介导的牙槽骨再生周围的免疫微环境，证实了巨噬细胞依赖性地增强再生效果。基于这一发现，开发了无定形磷酸锌钙（ACZP）纳米颗粒作为免疫调节纳米材料。ACZP可通过抗炎表型极化加速骨再生，具体方式是抑制内质网-线粒体偶联、减少病理性钙转移，并将巨噬细胞代谢从糖酵解转变为氧化磷酸化（OXPHOS），从而增强生物能量学。我们的结果表明，ACZP可抑制巨噬细胞中的IP3R/MCU途径，恢复其抗炎能力，并最终在新西兰白兔的牙槽骨缺损中取得显著效果。术后12周，ACZP组的缺损处几乎被70%的新形成骨组织填充。本研究阐明了ACZP材料在牙槽骨愈合动态过程中的免疫调节作用，为组织工程和再生医学领域的材料设计提供了新的见解和方法。
