牙周纤维
再生(生物学)
牙周膜干细胞
釉原蛋白
胶结作用
牙周炎
细胞生物学
牙科
化学
牙骨质
医学
碱性磷酸酶
生物
生物化学
牙本质
搪瓷漆
酶
作者
Jie Pan,Huizhong Tian,Siming Xu,Liwei Zhang,Jiandong Ding,Huijing Wang,Lin Yu,Wei Fu,Xin Liu
标识
DOI:10.1016/j.compositesb.2023.111162
摘要
Periodontitis is a growing clinical problem worldwide. Despite various approaches that have been devoted to repairing periodontal defects, the clinical outcomes are still limited due to the decline in tissue regenerative potential after periodontitis. Fortunately, chemically modified mRNA (modRNA)-based therapeutics have emerged as a promising strategy to combat incurable diseases. However, the use of modRNA for treating periodontitis is rare and challenging. Herein, a novel therapeutic mRNA platform that allows for sustained delivery and targeted osteogenesis and cementogenesis was developed for periodontal regeneration by combining a self-assembling PLA-PEG-PLA hydrogel and newly synthesized modRNA encoding amelogenin (AMELX) via in vitro transcription. The thermosensitive PLA-PEG-PLA hydrogel significantly prevented modRNA degradation and prolonged the release of encapsulated modRNA by forming an in situ hydrogel depot at 37 °C, resulting in sustained and strong expression of AMELX in human periodontal ligament stem cells (PDLSCs). Moreover, the AMELX modRNA exhibited a great capacity for promoting osteogenesis and cementogenesis of PDLSCs, as evidenced by elevated alkaline phosphatase (ALP) activity, calcium nodule formation, and osteogenesis- and cementogenesis-related gene expression (e.g., ALP, BMP2, CAP, BSP, COL1A1). As a result, after a single local injection, the PLA-PEG-PLA hydrogel enabled AMELX modRNA to persist and release at the defect site, thus successfully regenerating bone and periodontal ligament tissues in periodontal defects of rats. These findings provide a new approach for treating periodontal defects using self-assembling hydrogels to enable safe and effective delivery of AMELX modRNA, thereby offering various possibilities for functional tissue reconstruction with mRNA therapeutics.
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