Introduction: Cell-based tissue engineering is a promising method for dentin-pulp complex (DPC) regeneration. The challenges associated with DPC regeneration include the generation of a suitable microenvironment that facilitates the complete odontogenic differentiation of dental pulp stem cells (DPSCs) and the rapid induction of angiogenesis. Thus, the survival and subsequent differentiation of DPSCs are limited. Extracellular matrix (ECM)-like biomimetic hydrogels composed of self-assembling peptides (SAPs) were developed to provide an appropriate microenvironment for DPSCs. For functional DPC regeneration, the most important considerations are to provide an environment that promotes the adequate attachment of DPSCs and rapid vascularization of the regenerating pulp. Morphogenic signals in the form of growth factors (GFs) have been incorporated into SAPs to promote productive DPSC behaviors. However, the use of GFs has several drawbacks. We envision using a scaffold with SAPs coupled with long-term factors to increase DPSC attachment and vascularization as a method to address this challenge.
Methods: In this study, we developed synthetic material for an SAP-based scaffold with RGD- and vascular endothelial growth factor (VEGF)-mimetic peptide epitopes with the dual functions of dentin and pulp regeneration. DPSCs and human umbilical vein endothelial cells (HUVECs) were used to evaluate the biological effects of SAP-based scaffolds. Furthermore, the pulpotomized molar rat model was employed to test the reparative and regenerative effects of SAP-based scaffolds.
Results: This scaffold simultaneously presented RGD- and VEGF-mimetic peptide epitopes and provided a 3D microenvironment for DPSCs. DPSCs grown on this composite scaffold exhibited significantly improved survival and angiogenic and odontogenic differentiation in the multifunctionalized group in vitro. Histological and functional evaluations of a partially pulpotomized rat model revealed that the multifunctionalized scaffold was superior to other options with respect to stimulating pulp recovery and dentin regeneration in vivo.
Conclusion: Based on our data obtained with the functionalized SAP scaffold, a 3D microenvironment that supports stem cell adhesion and angiogenesis was generated that has great potential for dental pulp tissue engineering and regeneration.

Keywords: dentin-pulp complex regeneration, dental pulp stem cells, self-assembling peptides, cell adhesion, angiogenesis, multifunctionalization


中文翻译：

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RGD 和 VEGF 模拟肽表位功能化自组装肽水凝胶促进牙本质牙髓复合体再生


简介：基于细胞的组织工程是牙本质牙髓复合体（DPC）再生的一种有前途的方法。与 DPC 再生相关的挑战包括产生合适的微环境，促进牙髓干细胞 (DPSC) 的完全牙源分化和快速诱导血管生成。因此，DPSC 的存活和随后的分化是有限的。开发了由自组装肽（SAP）组成的类细胞外基质（ECM）仿生水凝胶，为DPSC提供合适的微环境。对于功能性 DPC 再生，最重要的考虑因素是提供一个促进 DPSC 充分附着和再生牙髓快速血管化的环境。生长因子 (GF) 形式的形态发生信号已被纳入 SAP 中，以促进生产性 DPSC 行为。然而，GF 的使用有几个缺点。我们设想使用具有 SAP 的支架加上长期因素来增加 DPSC 附着和血管化，作为应对这一挑战的方法。

方法：在本研究中，我们开发了基于 SAP 的支架的合成材料，该支架具有 RGD 和血管内皮生长因子 (VEGF) 模拟肽表位，具有牙本质和牙髓再生的双重功能。 DPSC 和人脐静脉内皮细胞 (HUVEC) 用于评估基于 SAP 的支架的生物学效应。此外，采用断髓磨牙大鼠模型来测试 SAP 支架的修复和再生效果。

结果：该支架同时呈现 RGD 和 VEGF 模拟肽表位，并为 DPSC 提供 3D 微环境。在该复合支架上生长的 DPSC 在体外多功能化组中表现出显着改善的存活率以及血管生成和牙源分化。对部分牙髓切断的大鼠模型的组织学和功能评估表明，多功能支架在刺激体内牙髓恢复和牙本质再生方面优于其他选择。

结论：根据我们使用功能化 SAP 支架获得的数据，生成了支持干细胞粘附和血管生成的 3D 微环境，这对于牙髓组织工程和再生具有巨大潜力。


Keywords:牙本质-牙髓复合体再生, 牙髓干细胞, 自组装肽, 细胞粘附, 血管生成, 多功能化