University of Nevada, Las Vegas, School of Dental Medicine, Las Vegas, Nevada.
University of Utah Health Science Center, School of Dentistry, Salt Lake City, Utah.
J Endod. 2020 Sep;46(9S):S19-S25. doi: 10.1016/j.joen.2020.06.039.
The ability to resolve pulpal inflammation to achieve predictable regeneration of the dentin-pulp complex has remained elusive and presents a challenge for clinicians and researchers. Although the dentin-pulp complex can react naturally to injury by forming a bridge of reparative dentin that protects the pulp from further damage, this process is significantly impaired if inflammation persists. Because the secretion of inflammatory cytokines by injured pulpal cells causes significant pain and discomfort to patients, it is critical to resolve pulpal inflammation in a timely manner so as to create a microenvironment conducive for pulpal healing and reparative dentin formation. The emergent field of regenerative endodontics has encouraged the development and application of biologically driven therapies that take advantage of the intrinsic healing capacities of host cells within dental pulp and the periapical complex.
These studies were designed to test the hypothesis that exposure to hypoxic conditions can modulate the production of inflammatory cytokines/factors by mesenchymal cells in vitro. A multi-domain peptide hydrogel system that is highly conducive for the growth and differentiation of tooth-derived stem cells was used for these studies. Stem cells from human exfoliated deciduous teeth (SHEDs) were first cultured within 3-dimensional hydrogel constructs and then challenged with hypoxic stresses via addition of HO.
MDP constructs were successfully generated, challenged with HO, decellularized and lyophilized, forming a potential biomaterial containing hypoxia induced repair molecules. The ability of cell-derived factors to convert the phenotype of lipopolysaccharide-primed macrophages from a proinflammatory to a pro-resolving state was examined in the presence of the lyophilized SHED cell constructs.
Our data suggest that hypoxia induced SHED cell products can be captured within the hydrogel system and may be useful in the resolution of pulpal inflammation to create a favorable microenvironment for regeneration of the dentin-pulp complex.
实现牙髓炎症的可控消退，从而预测性地再生牙本质-牙髓复合体，这一目标一直难以实现，对临床医生和研究人员来说仍是一个挑战。尽管牙髓复合体在受到损伤后，通过形成一层修复性牙本质来保护牙髓免受进一步的损伤，从而产生自然反应，但如果炎症持续存在，这种反应能力会显著受损。由于受损牙髓细胞分泌的炎症细胞因子会给患者带来显著的疼痛和不适，因此及时消退牙髓炎症对于创造有利于牙髓愈合和修复性牙本质形成的微环境至关重要。再生牙髓学这一新兴领域鼓励开发和应用生物学驱动疗法，利用牙髓和根尖周复合体中宿主细胞的固有愈合能力。
这些研究旨在检验以下假设，即在体外，缺氧条件可以调节间充质细胞产生炎症细胞因子/因子。本研究使用了一种高度有利于牙源性干细胞生长和分化的多结构域肽水凝胶系统。首先，将人脱落乳牙牙髓干细胞（SHED）培养在 3 维水凝胶构建体中，然后通过添加 H0 来对其进行缺氧应激处理。
成功地生成了 MDP 构建体，对其进行 H0 挑战，脱细胞和冻干，形成了一种潜在的含有缺氧诱导修复分子的生物材料。在冻干的 SHED 细胞构建体存在的情况下，研究了细胞衍生因子将脂多糖预刺激的巨噬细胞表型从促炎状态转变为促修复状态的能力。
我们的数据表明，缺氧诱导的 SHED 细胞产物可以被捕获在水凝胶系统中，并且可能有助于消退牙髓炎症，为牙本质-牙髓复合体的再生创造有利的微环境。
