Melatonin Engineering M2 Macrophage‐Derived Exosomes Mediate Endoplasmic Reticulum Stress and Immune Reprogramming for Periodontitis Therapy

Ya Cui; Shebin Hong; Yunhui Xia; Xiaojing Li; Xiaoya He; Xiangying Hu; Yaxin Li; Xudong Wang; Kaili Lin; Lixia Mao

doi:10.1002/advs.202302029

Advanced Science (Sep 2023)

Melatonin Engineering M2 Macrophage‐Derived Exosomes Mediate Endoplasmic Reticulum Stress and Immune Reprogramming for Periodontitis Therapy

Ya Cui,
Shebin Hong,
Yunhui Xia,
Xiaojing Li,
Xiaoya He,
Xiangying Hu,
Yaxin Li,
Xudong Wang,
Kaili Lin,
Lixia Mao

Affiliations

Ya Cui: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Shebin Hong: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Yunhui Xia: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Xiaojing Li: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Xiaoya He: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Xiangying Hu: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Yaxin Li: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Xudong Wang: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Kaili Lin: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China
Lixia Mao: Department of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai 200011 China

DOI: https://doi.org/10.1002/advs.202302029
Journal volume & issue: Vol. 10, no. 27
pp. n/a – n/a

Abstract

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Abstract Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play a crucial role in inflammatory response. An appropriate and timely transition from proinflammatory (M1) to anti‐inflammatory (M2) macrophages is indispensable for treating periodontitis. As M2 macrophage‐derived exosomes (M2‐exos) can actively target inflammatory sites and modulate immune microenvironments, M2‐exos can effectively treat periodontitis. Excessive endoplasmic reticulum stress (ER stress) and unfolded protein response (UPR) are highly destructive pathological characteristics during inflammatory periodontal bone loss. Although melatonin has antioxidant and anti‐inflammatory effects, studies focusing on melatonin ER stress modulation remain limited. This study fabricates engineered M2‐exos loading with melatonin (Mel@M2‐exos) for treating periodontitis. As a result, M2‐exos drive an appropriate and timely macrophage reprogramming from M1 to M2 type, which resolves chronic inflammation and accelerated periodontal healing. Melatonin released from Mel@M2‐exos rescues the osteogenic and cementogenic differentiation capacity in inflammatory human periodontal ligament cells (hPDLCs) by reducing excessive ER stress and UPR. Injectable gelatin methacryloyl (GelMA) hydrogels with sustained‐release Mel@M2‐exos accelerate periodontal bone regeneration in rats with ligation‐induced periodontitis. Taken together, melatonin engineering M2 macrophage‐derived exosomes are promising candidates for inflammatory periodontal tissue regeneration.

Published in Advanced Science

ISSN: 2198-3844 (Online)
Publisher: Wiley
Country of publisher: Germany
LCC subjects: Science
Website: https://onlinelibrary.wiley.com/journal/21983844

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