Citation: Zhiyuan Shen, Tianyi Li, Zijie Zhang, Jiani Liu, Jun Wu, Qing Li, Fulan Wei. Carbon monoxide-engineered M2 exosomes enhance osteoimmunology and promote alveolar bone regeneration[J]. Chinese Chemical Letters, ;2026, 37(7): 111641. doi: 10.1016/j.cclet.2025.111641 shu

Carbon monoxide-engineered M2 exosomes enhance osteoimmunology and promote alveolar bone regeneration

Zhiyuan Shen ^{a, b} ,
Tianyi Li ^{a, b} ,
Zijie Zhang ^{a, b} ,
Jiani Liu ^{a, b} ,
Jun Wu ^{c, d, *,} ,
Qing Li ^{a, b, *,} ,
Fulan Wei ^{a, b, *,}

a.
Department of Orthodontics & Oral and Maxillofacial Surgery & Pediatric Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Ji’nan 250012, China
b.
Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Ji’nan 250012, China
c.
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou 511400, China
d.
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China

junwuhkust@ust.hk

lq580202@sdu.edu.cn

weifl@email.sdu.edu.cn

Received Date: 6 May 2025
Revised Date: 20 July 2025
Accepted Date: 25 July 2025
Available Online: 26 July 2025

Figures(5)

Macrophage-derived exosomes have demonstrated considerable potential for promoting bone regeneration. This study proposes a novel engineered therapeutic strategy that utilizes carbon monoxide releasing prodrugs (TG-Fe CORMs) to selectively induce M2 macrophage polarization, thereby enhancing the production of M2 macrophage-derived exosomes (CO-M2-Exos). These exosomes have been observed to significantly promote osteogenesis and accelerate alveolar bone regeneration through the microRNA-21/Lhx8 signaling pathway. Notably, these exosomes possess several advantageous characteristics, including their capacity for remarkable regenerative effects, low immunogenicity, and high cellular uptake, which renders them promising cell-free therapy for addressing alveolar bone defects. Moreover, the scalable production of CO-M2-Exos successfully overcomes the significant challenges associated with traditional exosome-based therapies, such as the complexity of cell culture processes, the instability of phenotype, and the low yield of exosome production. This engineered approach offers a reliable, efficient, and cost-effective solution for clinical translation, particularly for promoting alveolar bone regeneration in cases of severe bone atrophy following tooth extraction.
- CO-M2-Exos,
- Carbon monoxide,
- Osteogenesis,
- miRNA-21,
- Lhx8,
- Alveolar bone
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