Development of a Treatment Concept for Dental Pulp Tissue Engineering

传统的根管治疗包括从根管系统中完全去除发炎或坏死的牙髓组织，用合成材料扩大、消毒和封闭空隙。然而，牙髓有几个重要的功能，因此牙齿的活力在这种手术后就会丧失。干细胞生物学和牙髓组织工程的最新进展以及维持牙齿活力的再生手术的临床报道可能是牙髓学范式转变的前奏，并导致未来我们能够再生牙髓的治疗策略的建立。自体干细胞的移植是一种很有前途的方法，但它受到细胞收获和扩增以及高成本等问题的阻碍。或者，可以考虑无细胞的方法，这涉及到常驻干细胞的募集、迁移、增殖和分化。这种再生过程的条件可以通过使用生物活性支架材料来优化，这种支架材料被放置在根管中，并且通过利用包裹在牙本质基质中的生长因子来进一步优化。为了提供一个有利于干细胞募集和新组织形成的环境，需要修改根管准备、灌洗和填充的方案。在拟议的项目中，我们打算建立一个基于生物学的根管治疗方法的协议。本应用程序的总体目标是建立牙髓再生程序，遵循细胞归巢概念。在不可逆的炎症或坏死组织情况下，部分或完全去除牙髓组织后，再生程序将包括1)根管消毒，2)通过edta调节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)将含有生长因子的材料重新插入根管；6)用生物活性水泥覆盖支架，然后将根管系统严密密封。这项工作有助于开发一种不需要外源干细胞或生长因子的工程牙髓治疗策略，因此可能很好地应用于再生牙髓学。

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.