Personalized bioprinting technology for de novo PDL regeneration

用于 PDL 从头再生的个性化生物打印技术

基本信息

批准号：
10667088
负责人：
GEORGE T.J HUANG
金额：
$ 42.35万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10667088
关键词：
3-Dimensional 3D Print Address Affect Algorithms Allogenic Animal Model Animals Ankylosis Anterior Autologous Back Behavior Biological Cell Count Cell Survival Cell Therapy Cell physiology Cell-Matrix Junction Cells Cementum Formation Characteristics Clinical Clinical Protocols Coupled Custom Data Data Set Decontamination Dental Dental Cementum Development Dorsal Edentulous Mouth Encapsulated Environment Failure Family suidae Fiber Functional Regeneration Future Gene Expression Generations Genes Histologic Histology Human Immunohistochemistry Implant In Vitro Individual Injury Investigation Jaw Knock-out Mandible Maxilla Mediating Medical Methods Microspheres Miniature Swine Modeling Natural regeneration Outcome Patients Periodontal Ligament Plants Population Printing Process Production Protocols documentation Regenerative Medicine SCID Mice Secure Services Shapes Source Surface Surgical Replantation Technology Tennessee Testing Thick Thinness Tissue Engineering Tissues Tooth Avulsion Tooth Loss Tooth Socket Tooth root structure Tooth structure Transplantation Trauma Work alveolar bone bioink bioprinting cell bank design in vitro regeneration in vivo in vivo Model innovation microCT mouse model osteogenic permanent tooth personalized medicine preservation stem cell technology stem cells subcutaneous tissue regeneration trauma centers

项目摘要

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.

抽象的恒牙撕脱是最严重的牙齿损伤之一。牙周膜 (PDL) 在撕脱过程中被损坏和污染以及再植后的结果撕脱的牙齿很差。使用 PDL 干细胞 (PDLSC) 的细胞疗法为我们提供了使撕脱牙齿的 PDL 再生的机会。最近的大型动物研究表明基于细胞的疗法治疗撕脱牙齿的前景。然而，目前还缺乏尖端组织工程技术的系统设计和部署最终将导致开发针对 de novo PDL 的个性化医疗方法撕脱牙齿的再生。在这里，我们建议采用新开发的两步法技术，即使用 Biosynspheres 和个性化干细胞 3D 生物打印介导的 PDL 再生。第一步涉及生产含有 PDLSC 的生物墨水封装在微球中，称为 PDLSC-Biosynspheres。第二步采用采用特定算法设计的定制 3D 生物打印机，可以打印一层 PDLSC- 生物合成球沿着其自然表面附着在已净化和裸露的牙根上地形，具有所需的均匀厚度，以便整个根部的 PDL 再生表面。我们假设撕脱牙齿上丢失的 PDL 可以使用以下方法从头再生：使用 PDLSC-Biosynspheres 进行个性化生物打印。在目标 1 中，我们将优化生成 PDLSC-Biosynspheres 并在打印到体外根表面和体内已建立的 SCID 小鼠模型。在目标 2 中，我们将利用一个简单的迷你猪模型来表征功能性 PDL 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根部一致的 PDL 再生，这将产生初步的数据为未来 R01 应用中更广泛的大型动物研究奠定了基础。这重大临床影响是在该中心建立牙科创伤管理中心的潜力田纳西州再生医学研究所 (TennIRM) 重新种植撕脱牙齿，旨在成功的长期有利结果。未来的努力将包括建立干细胞银行业务以促进和确保此类医疗疗法的细胞来源。