State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
Adv Sci (Weinh). 2024 May;11(18):e2309562. doi: 10.1002/advs.202309562. Epub 2024 Mar 9.
The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose viscoelasticity (e.g., stress relaxation) during periodontitis or dental trauma, which disrupt cell-extracellular matrix (ECM) interactions and accelerates tissue damage. Here, Pluronic F127 diacrylate (F127DA) hydrogels with PDL-matched stress relaxation rates and high elastic moduli are developed. The hydrogel viscoelasticity is modulated without chemical cross-linking by controlling precursor concentrations. Under cytomechanical loading, F127DA hydrogels with fast relaxation rates significantly improved the fibrogenic differentiation potential of PDL stem cells (PDLSCs), while cells cultured on F127DA hydrogels with various stress relaxation rates exhibited similar fibrogenic differentiation potentials with limited cell spreading and traction forces under static conditions. Mechanically, faster-relaxing F127DA hydrogels leveraged cytomechanical loading to activate PDLSC mechanotransduction by upregulating integrin-focal adhesion kinase pathway and thus cytoskeletal rearrangement, reinforcing cell-ECM interactions. In vivo experiments confirm that faster-relaxing F127DA hydrogels significantly promoted PDL repair and reduced abnormal healing (e.g., root resorption and ankyloses) in delayed replantation of avulsed teeth. This study firstly investigated how matrix nonlinear viscoelasticity influences the fibrogenesis of PDLSCs under mechanical stimuli, and it reveals the underlying mechanobiology, which suggests novel strategies for PDL regeneration.
机械敏感组织（如牙周韧带[PDLs]）的黏弹性对于维持机械内稳态至关重要。不幸的是，PDLs 在牙周炎或牙外伤期间很容易失去黏弹性（例如，应力松弛），这会破坏细胞-细胞外基质（ECM）相互作用并加速组织损伤。本研究开发了具有与 PDL 匹配的应变速率和高弹性模量的 Pluronic F127 二丙烯酸酯（F127DA）水凝胶。通过控制前体浓度，可以在不进行化学交联的情况下调节水凝胶的黏弹性。在细胞机械加载下，具有快速松弛率的 F127DA 水凝胶显著提高了牙周韧带干细胞（PDLSCs）的成纤维分化潜能，而在静态条件下，细胞在具有不同应变速率的 F127DA 水凝胶上培养时，由于细胞铺展和牵引力有限，其成纤维分化潜能相似。从力学角度来看，更快松弛的 F127DA 水凝胶通过上调整合素-粘着斑激酶通路，从而增强细胞-ECM 相互作用，利用细胞机械加载来激活 PDLSC 力学转导，从而上调整合素-粘着斑激酶通路，从而激活 PDLSC 力学转导。体内实验证实，更快松弛的 F127DA 水凝胶显著促进了牙周韧带的修复，并减少了延迟再植牙中异常愈合（如牙根吸收和骨粘连）的发生。本研究首次研究了基质非线性黏弹性如何在机械刺激下影响 PDLSCs 的成纤维生成，揭示了其潜在的力学生物学机制，为牙周韧带再生提供了新的策略。
