A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs.
A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs.
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DOI：
10.1038/s41598-017-02532-3
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发表时间：
2017-06-12
影响因子：
4.6
通讯作者：
Bertassoni LE
中科院分区：
文献类型：
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作者：
Athirasala A;Lins F;Tahayeri A;Hinds M;Smith AJ;Sedgley C;Ferracane J;Bertassoni LE
牙髓再生是根管治疗的有效治疗策略，但牙髓组织的血管化是根管治疗中的一个主要障碍。在这里，我们展示了一种新的策略，工程师预血管化，细胞负载水凝胶牙髓样组织结构在全长根管牙髓再生。我们利用明胶甲基丙烯酰（GelMA）水凝胶与可调的物理和机械性能，以确定微环境条件（微观结构，降解，溶胀和弹性模量），增强活力，扩展和增殖的封装成牙本质细胞样细胞（OD 21），内皮细胞集落形成细胞（ECFC）的内皮单层的形成。具有较高聚合物浓度（15%w/v）和刚度的GelMA水凝胶增强了OD 21细胞活力、铺展和增殖，以及内皮细胞铺展和单层形成。然后，我们通过在拔出的牙齿的根管中分配OD 21细胞负载的GelMA水凝胶预聚物并在整个根管中制造500 μm的通道来制造预血管化的全长牙髓样组织构建体。将ECFC接种到微通道中，成功形成单层，并在培养7天内发生血管生成发芽。总之，所提出的方法是一种简单而有效的策略，用于预血管化牙髓结构的工程化，提供潜在的有益的转化结果。
The requirement for immediate vascularization of engineered dental pulp poses a major hurdle towards successful implementation of pulp regeneration as an effective therapeutic strategy for root canal therapy, especially in adult teeth. Here, we demonstrate a novel strategy to engineer pre-vascularized, cell-laden hydrogel pulp-like tissue constructs in full-length root canals for dental pulp regeneration. We utilized gelatin methacryloyl (GelMA) hydrogels with tunable physical and mechanical properties to determine the microenvironmental conditions (microstructure, degradation, swelling and elastic modulus) that enhanced viability, spreading and proliferation of encapsulated odontoblast-like cells (OD21), and the formation of endothelial monolayers by endothelial colony forming cells (ECFCs). GelMA hydrogels with higher polymer concentration (15% w/v) and stiffness enhanced OD21 cell viability, spreading and proliferation, as well as endothelial cell spreading and monolayer formation. We then fabricated pre-vascularized, full-length, dental pulp-like tissue constructs by dispensing OD21 cell-laden GelMA hydrogel prepolymer in root canals of extracted teeth and fabricating 500 µm channels throughout the root canals. ECFCs seeded into the microchannels successfully formed monolayers and underwent angiogenic sprouting within 7 days in culture. In summary, the proposed approach is a simple and effective strategy for engineering of pre-vascularized dental pulp constructs offering potentially beneficial translational outcomes.