Gu Yingzhi, Hu Yang, Huang Shengyuan, Ruiz Sunniva, Kawai Toshihisa, Bai Yuxing, Han Xiaozhe
Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.
Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
Biology (Basel). 2023 Jul 10;12(7):976. doi: 10.3390/biology12070976.
The immune system plays an important role in the skeletal system during bone repair and regeneration. The controlled release of biological factors from the immune system could facilitate and optimize the bone remodeling process through the regulation of the activities of bone cells. This study aimed to determine the effect of the controlled delivery of immunomodulatory biologicals on bone regeneration. Immunostimulatory cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) and glucosylxanthone Mangiferin (MAG)-embedded microbeads were incubated with -challenged splenocytes, or co-cultured with RAW264.7 cells. The effect of CpG ODN/MAG-containing microbeads on bone regeneration was then tested in vivo in a mouse alveolar bone defect model. The results demonstrated that MAG significantly antagonized proliferation and reduced the live/dead cell ratio. After the addition of CpG ODN + MAG microbeads, anti-inflammatory cytokines IL-10 and IL-4 were upregulated on day 2 but not day 4, whereas pro-inflammatory cytokine IL-1β responses showed no difference at both timepoints. RANKL production by splenocytes and TRAP+ cell formation of RAW264.7 cells were inhibited by the addition of CpG ODN + MAG microbeads. Alveolar bony defects, filled with CpG ODN + MAG microbeads, showed significantly increased new bone after 4 weeks. In summary, this study evaluated a new hydrogel-based regimen for the local delivery and controlled release of biologicals to repair and regenerate alveolar bony defects. The combined CpG ODN + MAG treatment may promote alveolar bone regeneration through the anti-microbial/anti-inflammatory effects and the inhibition of RANKL-mediated osteoclastogenesis.
在骨修复和再生过程中，免疫系统在骨骼系统中发挥着重要作用。免疫系统生物因子的可控释放可通过调节骨细胞的活性来促进和优化骨重塑过程。本研究旨在确定免疫调节生物制剂的可控递送对骨再生的影响。将免疫刺激型胞嘧啶 - 磷酸 - 鸟嘌呤寡脱氧核苷酸（CpG ODN）和嵌入葡萄糖基黄酮知母宁（MAG）的微珠与受刺激的脾细胞孵育，或与RAW264.7细胞共培养。然后在小鼠牙槽骨缺损模型中体内测试含CpG ODN/MAG的微珠对骨再生的影响。结果表明，MAG显著拮抗增殖并降低活/死细胞比率。添加CpG ODN + MAG微珠后，抗炎细胞因子IL-10和IL-4在第2天上调，但在第4天未上调，而促炎细胞因子IL-1β反应在两个时间点均无差异。添加CpG ODN + MAG微珠可抑制脾细胞产生RANKL和RAW264.7细胞形成TRAP+细胞。填充有CpG ODN + MAG微珠的牙槽骨缺损在4周后显示出新骨显著增加。总之，本研究评估了一种基于水凝胶的新方案，用于生物制剂的局部递送和可控释放，以修复和再生牙槽骨缺损。联合使用CpG ODN + MAG治疗可能通过抗菌/抗炎作用和抑制RANKL介导的破骨细胞生成来促进牙槽骨再生。
