Liu Honghong, Zhu Dongao, Lang Lv, Liu Mingkun, Yang Zongcheng, Zhang Zhihong, Shen Zuojun
Department of Stomatology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
College of Stomatology, Bengbu Medical University, Anhui, Bengbu, 233000, China.
Mater Today Bio. 2025 Aug 25;34:102246. doi: 10.1016/j.mtbio.2025.102246. eCollection 2025 Oct.
Peri-implantitis (PI) is a major cause of implant restoration failure, necessitating therapeutic strategies that integrate bone regeneration and anti-inflammatory effects. Despite advances in treatment, no existing agents simultaneously address both objectives. Exosomes (Exos), as key mediators of intercellular communication, have demonstrated dual anti-inflammatory and osteogenic capacities through microRNA (miRNA) delivery; however, their potential in PI therapy remains unexplored. This study evaluates the therapeutic efficacy of a composite hydrogel loaded with human umbilical cord blood-derived exosomes (UCB-Exos) in PI treatment, focusing on its dual anti-inflammatory and bone-regenerative functions, and elucidates the underlying molecular mechanisms. experiments revealed that UCB-Exos (30 μg/mL) enhanced the proliferation, migration, and osteogenic differentiation of BMSCs. Additionally, UCB-Exos suppressed pro-inflammatory cytokine expression (TNF-α and IL-1β) in RAW264.7 cells while upregulating anti-inflammatory IL-10. An nHAP-GelMA/AlgMA (nGA) composite hydrogel was developed, demonstrating a porous structure, excellent biocompatibility, and sustained UCB-Exos release. , rat PI models were established to assess therapeutic outcomes. Micro-CT analysis following treatment with UCB-Exos-loaded nGA hydrogel showed significant PI bone regeneration, while H&E staining revealed reduced inflammatory cell infiltration. Furthermore, UCB-Exos could inhibit the expression of TNF-α and IL-1β and promote the expression of IL-10 in PI gingival tissues. High-throughput small RNA sequencing identified miR-182-5p as a key upregulated miRNA in the UCB-Exos group. Target gene prediction and dual-luciferase reporter assays confirmed that miR-182-5p directly targets the 3'UTR of MYD88. UCB-Exos, via miR-182-5p delivery, inhibited the MYD88/NF-κB signaling pathway, thereby promoting BMSCs osteogenic differentiation. These effects were reversed by miR-182-5p inhibitors. This study establishes UCB-Exos as a promising therapeutic agent for PI, demonstrating dual bone-regenerative and anti-inflammatory functions mediated by miR-182-5p inhibition of the MYD88/NF-κB pathway. These findings broaden the scope of UCB-Exos applications and offer a novel approach to the further development of medications for treating PI.
种植体周围炎（PI）是种植体修复失败的主要原因，因此需要能整合骨再生和抗炎作用的治疗策略。尽管治疗取得了进展，但目前尚无药物能同时实现这两个目标。外泌体（Exos）作为细胞间通讯的关键介质，已通过递送微小RNA（miRNA）展现出抗炎和成骨双重能力；然而，其在PI治疗中的潜力仍未得到探索。本研究评估了负载人脐带血来源外泌体（UCB-Exos）的复合水凝胶在PI治疗中的疗效，重点关注其抗炎和骨再生双重功能，并阐明其潜在的分子机制。实验表明，UCB-Exos（30μg/mL）可促进骨髓间充质干细胞（BMSCs）的增殖、迁移和成骨分化。此外，UCB-Exos可抑制RAW264.7细胞中促炎细胞因子的表达（TNF-α和IL-1β），同时上调抗炎因子IL-10。开发了一种nHAP-GelMA/AlgMA（nGA）复合水凝胶，其具有多孔结构、良好的生物相容性和持续的UCB-Exos释放能力。随后，建立大鼠PI模型以评估治疗效果。用负载UCB-Exos的nGA水凝胶治疗后的显微CT分析显示PI处有明显的骨再生，而苏木精-伊红染色显示炎症细胞浸润减少。此外，UCB-Exos可抑制PI牙龈组织中TNF-α和IL-1β的表达，并促进IL-10的表达。高通量小RNA测序确定miR-182-5p是UCB-Exos组中一个关键的上调miRNA。靶基因预测和双荧光素酶报告基因检测证实miR-182-5p直接靶向MYD88的3'非翻译区（UTR）。UCB-Exos通过递送miR-182-5p抑制MYD88/NF-κB信号通路，从而促进BMSCs的成骨分化。这些作用可被miR-182-5p抑制剂逆转。本研究证实UCB-Exos是一种有前景的PI治疗药物，通过miR-182-5p抑制MYD88/NF-κB途径发挥骨再生和抗炎双重功能。这些发现拓宽了UCB-Exos的应用范围，并为进一步开发治疗PI的药物提供了新方法。
