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A 3D In-vitro model of the human dentine interface shows long-range osteoinduction from the dentine surface
International Journal of Oral Science ( IF 10.8 ) Pub Date : 2024-05-11 , DOI: 10.1038/s41368-024-00298-9
William Macalester 1, 2 , Asme Boussahel 1 , Rafael O Moreno-Tortolero 2, 3, 4 , Mark R Shannon 1 , Nicola West 5 , Darryl Hill 1 , Adam Perriman 1
Affiliation  

Emerging regenerative cell therapies for alveolar bone loss have begun to explore the use of cell laden hydrogels for minimally invasive surgery to treat small and spatially complex maxilla-oral defects. However, the oral cavity presents a unique and challenging environment for in vivo bone tissue engineering, exhibiting both hard and soft periodontal tissue as well as acting as key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems, which will impact on cell fate and subsequent treatment efficacy. Herein, we design and bioprint a facile 3D in vitro model of a human dentine interface to probe the effect of the dentine surface on human mesenchymal stem cells (hMSCs) encapsulated in a microporous hydrogel bioink. We demonstrate that the dentine substrate induces osteogenic differentiation of encapsulated hMSCs, and that both dentine and β-tricalcium phosphate substrates stimulate extracellular matrix production and maturation at the gel-media interface, which is distal to the gel-substrate interface. Our findings demonstrate the potential for long-range effects on stem cells by mineralized surfaces during bone tissue engineering and provide a framework for the rapid development of 3D dentine-bone interface models.



中文翻译:


人类牙本质界面的 3D 体外模型显示牙本质表面的长程骨诱导



针对牙槽骨丢失的新兴再生细胞疗法已开始探索使用充满细胞的水凝胶进行微创手术,以治疗小型且空间复杂的上颌口腔缺陷。然而,口腔为体内骨组织工程提供了一个独特且具有挑战性的环境,表现出硬牙周组织和软牙周组织,并作为许多与外部环境和体内系统相互作用的不同微生物群落的关键生物群落,这将影响细胞命运和后续治疗效果。在此,我们设计并生物打印了一个简单的人体牙本质界面 3D 体外模型,以探讨牙本质表面对封装在微孔水凝胶生物墨水中的人间充质干细胞 (hMSC) 的影响。我们证明牙本质基质诱导封装的 hMSC 的成骨分化,并且牙本质和 β-磷酸三钙基质都刺激细胞外基质在凝胶-介质界面处的产生和成熟,该界面远离凝胶-基质界面。我们的研究结果证明了骨组织工程过程中矿化表面对干细胞产生长期影响的潜力,并为 3D 牙本质-骨界面模型的快速开发提供了框架。

更新日期:2024-05-11
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