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Harnessing Mechanical Stress with Viscoelastic Biomaterials for Periodontal Ligament Regeneration

ADVANCED SCIENCE(2024)

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摘要
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. Viscoelastic F127DA hydrogels with periodontal ligament (PDL)-matched stress relaxation rates significantly enhance the fibrogenic differentiation of PDL stem cells under cytomechanical loading. Mechanically, viscoelastic F127DA hydrogels harness mechanical stress to reinforce cell-matrix interactions by activating integrin-focal adhesion kinase-cytoskeleton linkages and exhibit potent therapeutic effects on PDL injuries in the delayed replantation of avulsed teeth. image
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关键词
F127 hydrogels,mechanical regulation,periodontal ligaments,viscoelastic hydrogels,viscoelasticity
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