Development of a Treatment Concept for Dental Pulp Tissue Engineering

传统的根管治疗包括将炎症或坏死的牙髓组织从根管系统中完全移除，扩大，消毒，并用合成材料填充空洞。然而，牙髓发挥着几个重要的功能，因此牙齿的活力在这样的过程中失去了。干细胞生物学和牙髓组织工程的最新进展，以及再生手术维持牙齿活力的临床报道，可能是牙髓学范式转变的前奏，并导致建立使我们能够在未来再生牙髓的治疗策略。虽然移植自体干细胞是一种很有前途的策略，但它受到细胞采集和扩增以及高昂成本的阻碍。或者，可以考虑采用无细胞方法，这涉及到常驻干细胞的招募、迁移、增殖和分化。通过使用生物活性支架材料，并进一步利用包裹在牙本质基质中的生长因子，可以优化这种再生过程的条件。将需要修改根管准备、冲洗和充填方案，以便提供有利于干细胞招募和新组织形成的环境。在拟议的项目中，我们打算建立一个基于生物学的方法来进行牙髓治疗的方案。这项应用的总体目标是建立一种遵循细胞归巢概念的牙髓再生程序。在不可逆炎症或坏死组织的情况下部分或完全切除牙髓组织后，再生过程将包括1)根管消毒，2)通过EDTA处理根管牙本质释放生长因子，3)从根管收集含有生长因子的冲洗液，4)与能够结合生长因子的生物材料混合，5)将携带生长因子的材料重新插入根管，6)用生物活性粘固剂覆盖支架，然后紧密封闭根管系统。这项工作可能有助于开发一种不需要应用外源干细胞或生长因子的牙髓工程治疗策略，因此可能非常适用于再生牙髓治疗。

Conventional root canal treatment involves the complete removal of inflamed or necrotic pulp tissue from the root canal system, enlargement, disinfection and obturation of the void with a synthetic material. However, the dental pulp, which fulfils several important functions, and thus tooth vitality are lost after such a procedure. Recent advances in stem cell biology and dental pulp tissue engineering as well as clinical reports of regenerative procedures to sustain tooth vitality might be the prelude of a paradigm shift in endodontics and lead to the establishment of treatment strategies enabling us to regenerate dental pulp in the future. Whereas implantation of autologous stem cells is a promising strategy, it is hampered by issues of cell harvest and expansion as well as high cost. Alternatively, cell-free approaches could be considered, which involve the recruitment, migration, proliferation and differentiation of resident stem cells. The conditions for such a regenerative procedure might be optimized by the use of a bioactive scaffold material, which is placed into the root canal, and furthermore by taking advantage of growth factors entrapped in the dentin matrix. Modified protocols for root canal preparation, irrigation and filling will be required in order to provide an environment that is conducive for stem cell recruitment and new tissue formation. In the proposed project, we intend to establish a protocol for a biology-based approach to endodontic treatment. The overall goal of this application is to establish a procedure for dental pulp regeneration, which follows the cell-homing concept. After partial or complete removal of pulp tissue in case of irreversibly inflamed or necrotic tissue, a regenerative procedure will include 1) disinfection of the root canal, 2) release of growth factors by EDTA-conditioning of root canal dentin, 3) collection of irrigation solution with growth factors from the root canal, 4) mixture with a biomaterial capable of growth factor-binding, 5) re-insertion of growth-factor-laden material into the root canal and 6) coverage of the scaffold with a bioactive cement followed by tight sealing of the canal system. This work could contribute to the development of a treatment strategy to engineer dental pulp which does not require the application of exogenous stem cells or growth factors and which might thus be well applicable in regenerative endodontics.