Department of Prosthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, 200011, No. 639 Zhizaoju Road, Shanghai, China.
National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, 200011, No. 639 Zhizaoju Road, Shanghai, China.
Adv Healthc Mater. 2023 Nov;12(28):e2301366. doi: 10.1002/adhm.202301366. Epub 2023 Aug 11.
Periodontitis is a prevalent dental disease marked by progressive destruction of tooth-supporting tissues, and the recovery of bone defects after periodontitis remains challenging. Although stem cell-based therapy is a promising treatment for periodontal tissue regeneration, the function of mesenchymal stem cells is constantly impaired by the inflammatory microenvironment, leading to compromised treatment outcomes. Herein, calcitonin gene-related peptide (CGRP)-loaded porous microspheres (PMs) are prepared to protect bone marrow mesenchymal stem cells (BMSCs) against inflammatory mediators in periodontitis. The released CGRP can effectively ameliorate the inflammation-induced dysfunction of BMSCs, which may involve suppressing the ROS (reactive oxygen species)/NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3)/Caspase-1 (CASP1) pathway. Moreover, the porous architecture of PMs provides effective cell-carrying capacity and physical protection for BMSCs during transplantation. In vivo experiments demonstrate that CGRP/BMSC-loaded PMs can effectively inhibit inflammation and improve osteogenic activity, resulting in better periodontal bone regeneration. This study focuses on the protection of stem cell function in the inflammatory microenvironment, which is important for stem cell-mediated tissue regeneration and repair under inflammatory conditions.
牙周炎是一种常见的牙科疾病，其特征是牙齿支持组织的进行性破坏，牙周炎后骨缺损的恢复仍然具有挑战性。虽然基于干细胞的治疗是牙周组织再生的一种有前途的治疗方法，但间充质干细胞的功能经常受到炎症微环境的损害，导致治疗效果不佳。在此，载降钙素基因相关肽（CGRP）的多孔微球（PMs）被制备用于保护骨髓间充质干细胞（BMSCs）免受牙周炎中炎症介质的侵害。释放的 CGRP 可以有效改善炎症诱导的 BMSCs 功能障碍，这可能涉及抑制 ROS（活性氧）/NLRP3（NOD、LRR 和 pyrin 结构域包含蛋白 3）/Caspase-1（CASP1）途径。此外，PMs 的多孔结构在移植过程中为 BMSCs 提供了有效的细胞承载能力和物理保护。体内实验表明，载 CGRP/BMSC 的 PMs 可有效抑制炎症并提高成骨活性，从而实现更好的牙周骨再生。本研究重点关注在炎症微环境中保护干细胞功能，这对于炎症条件下基于干细胞的组织再生和修复至关重要。
