School of Cellular and Molecular Medicine, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, United Kingdom.
Bristol Centre for Functional Nanomaterials, HH Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol, United Kingdom.
Int J Oral Sci. 2024 May 11;16(1):37. doi: 10.1038/s41368-024-00298-9.
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.
新兴的再生细胞疗法开始探索使用细胞负载水凝胶进行微创外科手术,以治疗小型和空间复杂的上颌骨-口腔缺陷。然而,口腔为体内骨组织工程提供了一个独特而具有挑战性的环境,同时具有坚硬和柔软的牙周组织,并作为许多不同微生物群落的关键生物群落,与外部环境和内部身体系统相互作用,这将影响细胞命运和随后的治疗效果。在这里,我们设计并生物打印了一种简单的人牙本质界面的 3D 体外模型,以探究牙本质表面对包埋在微孔水凝胶生物墨水内的人间充质干细胞 (hMSC) 的影响。我们证明了牙本质基质诱导包埋的 hMSC 发生成骨分化,牙本质和 β-磷酸三钙基质都刺激凝胶-培养基界面处细胞外基质的产生和成熟,该界面远离凝胶-基底界面。我们的研究结果表明,在骨组织工程过程中,矿化表面对干细胞具有远程影响的潜力,并为快速开发 3D 牙本质-骨界面模型提供了框架。