Personalized bioprinting technology for de novo PDL regeneration

摘要 恒牙撕脱是最严重的牙外伤之一。牙周膜 (PDL)在撕脱过程中受损和污染， 拔牙是穷人。使用PDL干细胞（PDLSC）的基于细胞的治疗为我们提供了 再生的机会撕脱牙的PDL。最近的大型动物研究表明 以细胞为基础的治疗方法治疗撕脱牙的前景。然而，缺乏 系统的设计和部署的类型的尖端组织工程技术， 最终将为新发PDL开发个性化的药物治疗方法 再生的牙齿。在这里，我们建议将新开发的两步 技术，即使用Biosynspheres和个性化3D生物打印干细胞- 介导的PDL再生。第一步涉及生产含有PDLSC的生物墨水 包封在微球中，称为PDLSC-Biosynspheres。第二步采用 定制的3D生物打印机设计有特定的算法，可以打印一层PDLSC- 将生物合成球贴附在经过净化和裸露的牙根自然表面上 拓扑结构，具有用于整个根上PDL再生的所需和均匀的厚度 面我们假设，脱落牙齿的PDL可以通过使用再生剂来重新再生。 使用PDLSC-Biosynspheres进行个性化生物打印。在目标1中，我们将优化 PDLSC-Biosynspheres，并在印刷到 在体外牙根表面和与建立的SCID小鼠模型在体内。在目标2中，我们将利用 一个简单的小型猪模型，以表征功能性PDL在体内的再生。我们 预计PDLSC-Biosynspheres和个性化3D生物打印的结合 技术将导致一致的PDL再生的根，这将产生初步的 这些数据为将来R 01应用中更广泛的大型动物研究奠定了基础。的 重大的临床影响是建立一个牙科创伤管理中心的潜力， 田纳西州再生医学研究所（田纳西州）再植撕脱牙，旨在 取得长期的良好成果。未来的奋进将包括建立干细胞 银行以促进和确保用于这种医学治疗的细胞来源。

ABSTRACT Avulsion of permanent teeth is one of the most serious dental injuries. The periodontal ligament (PDL) is damaged and contaminated during avulsion and the outcome after replantation of the avulsed teeth is poor. Cell-based therapy using PDL stem cells (PDLSCs) provides us with the opportunity to regenerate the PDL of avulsed teeth. Recent large animal studies have shown promise of cell-based therapies for managing avulsed teeth. However, there is a lack of systematic design and deployment of the type of cutting-edge tissue engineering technology that would ultimately lead to development of a personalized medicine approach for the de novo PDL regeneration of avulsed teeth. Here we propose to incorporate a newly developed, two-step technology, namely the use of Biosynspheres and personalized 3D-bioprinting for stem cell- mediated PDL regeneration. The first step involves the production of bio-ink containing PDLSCs encapsulated in microspheres, termed PDLSC-Biosynspheres. The second step employs a custom-made 3D-bioprinter designed with specific algorithms that can print a layer of PDLSC- Biosynspheres onto the decontaminated and denuded tooth root following its natural surface topography, with a desired and uniformed thickness for PDL regeneration on the entire root surface. We hypothesize that the lost PDL on avulsed teeth can be regenerated de novo using personalized bioprinting with PDLSC-Biosynspheres. In Aim 1, we will optimize the generation of PDLSC-Biosynspheres and characterize their biological behaviors after being printed onto the root surface in vitro and with an established SCID mouse model in vivo. In Aim 2, we will utilize a simple mini-swine model to characterize the regeneration of functional PDL in vivo. We anticipate that the combination of PDLSC-Biosynspheres and personalized 3D-bioprinting technology will result in consistent PDL regeneration on the root, which will generate preliminary data that sets the stage for more extensive large animal studies in a future R01 application. The significant clinical impact is the potential to establish a Dental Trauma Management Center at the Tennessee Institute of Regenerative Medicine (TennIRM) for replanting avulsed teeth aiming at successful long-term favorable outcomes. Future endeavor will include establishing stem cell banking to facilitate and secure the cell source for such medical therapies.