PFI:AIR-TT: Preclinical evaluation of bioactive tailored amorphous multiporous (TAMP) powder for the treatment of dentin hypersensitivity

该PFI：AIR技术翻译项目专注于翻译最新开发的用于修复受损牙本质和牙髓组织的技术，这是治疗牙本质过敏症（DH）所需的。DH是一种牙科疾病，在大多数人一生中的某个时候会造成严重的疼痛。目前可用的产品仅试图暂时治疗症状，并且没有持久的治疗方法。本项目主要研究纳米-大孔玻璃制备技术及新型生物活性材料在牙体组织再生中的应用。由此产生的玻璃，具有定制的无定形多孔（TAMP）结构，促进骨骼和软组织的生长。 该项目将产生新的TAMP组合物，并建立其再生受损牙本质和牙髓组织的潜力，以治疗DH。所选的TAMP粉末包含互连的纳米-大孔隙，可以根据所需的表面积进行定制，具有从源头上解决问题的独特潜力。因此，当放置在体内时，适当组成的TAMP粉末可以以受控的方式提供治疗离子，提供预期封闭牙本质小管的微环境，以比目前可用的产品更有效地停止疼痛症状。更重要的是，新的TAMP粉末还有望刺激细胞的组织再生，以实现持久的治疗。相比之下，该市场空间中的现有产品，可在柜台上或通过处方获得，没有尝试使受损组织再生。 该项目解决了从研究发现到商业应用的以下技术差距。基于硅酸钙的简单TAMP粉末在实验室测试中显示出骨形成细胞的增殖，并且在动物体内测试中也显示出骨再生和软组织再生。然而，其再生牙齿组织（牙本质和牙髓）的能力的证明一直缺乏。该项目试图获得TAMP粉末用于牙齿组织再生的治疗能力的证据，然后为临床试验做准备。它还在开发新的组合物，将不同治疗的益处联合收割机结合在一种产品中。例如，正在制造新型TAMP粉末，其中氟离子、锌离子和钾离子嵌入硅酸盐玻璃的分子结构中，以在DH部位提供氟离子、促进再生的锌离子和使疼痛感测神经脱敏的钾离子的持久供应。此外，正在进行测试以评估牙髓干细胞的体外分化，以及植入小鼠模型中的TAMP硅酸盐上的牙髓-牙本质复合物的体内形成。有了这些知识，组合物被优化，以实现更高的粘附性和更快的咬合层以及牙髓-牙本质组织再生。这项从研究发现到商业现实的技术转化是由玻璃科学家领导的团队努力，他在之前的NSF支持研究下开发了TAMP制造技术组合，以及具有牙齿组织再生专业知识的牙髓病学家，一位是细胞生物学家，具有细胞对TAMP材料反应的专业知识，另一位是医疗保健行业专家，具有生物医学产品早期商业化的经验。在其过程中，该项目直接培训三名研究生，通过结合材料工程，细胞生物学和牙科科学的跨学科方法进行使用启发式研究和实际问题解决。创新的TAMP技术及其潜在的社会影响的结合已经引起了广泛的学生兴趣，这将通过该项目的更明确的结果进一步扩大。

This PFI: AIR Technology Translation project focuses on translating recently developed technology for the regeneration of damaged dentin and pulp tissue, which is needed for the cure of dentin hypersensitivity (DH). DH is a dental condition that inflicts severe pain in majority of people sometime during their lifetime. The currently available products attempt only to treat the symptoms temporarily, and there is no lasting cure of the problem. This project focuses on nano-macro porous glass fabrication technology and applying a new class of bioactive materials to the regeneration of dental tissue. The resulting glasses, which have tailored amorphous multiporous (TAMP) structure, promote the growth of bone as well as soft tissue. The project will result in new TAMP compositions and establish their potential for the regeneration of damaged dentin and pulp tissue to cure DH. The selected TAMP powders that comprise of interconnected nano-macro porosity, which can be tailored to desired surface area, have the unique potential to cure the problem at its source. Consequently, when placed inside the body, a TAMP powder of appropriate composition can supply therapeutic ions in a controlled manner, providing a microenvironment that is expected to occlude dentin tubules to stop the painful symptoms more effectively than currently available products. More importantly, the new TAMP powders are also expected to stimulate tissue regeneration by the cells for a lasting cure. In contrast, the present products in this market space, available over the counter or by prescription, make no attempt to regenerate damaged tissue. The project addresses the following technology gap(s) as it translates from research discovery toward commercial application. A simple TAMP powder based on calcium silicate has shown proliferation of bone forming cells in laboratory tests and also regeneration of bone and soft tissue regeneration under in vivo tests in animals. However, a demonstration of its ability to regenerate dental tissue (dentin and pulp) has been lacking. The project attempts to obtain evidence for the therapeutic capabilities of TAMP powder for dental tissue regeneration, and thereafter prepare it for clinical trials. It is also developing new compositions that combine the benefits of different treatments in one product. For example, novel TAMP powders with fluoride, zinc and potassium ions embedded within the molecular structure of silicate glass are being fabricated, to provide a lasting supply of fluoride ions at the site of DH, zinc ions that promote regeneration, and potassium ions that desensitize pain-sensing nerves. Further, tests are being performed to assess in vitro differentiation of dental pulp stem cells, and in vivo formation of pulp-dentin complex on TAMP silicates implanted in a mouse model. With this knowledge compositions are optimized for more adherent and faster developing occlusion layer as well as pulp-dentin tissue regeneration.This technology translation from research discovery toward commercial reality is a team effort led by a glass scientist who developed the TAMP fabrication technology portfolio under prior NSF supported research, together with an endodontist with expertise in dental tissue regeneration, a cell biologist with expertise in cell response to TAMP materials, and a healthcare industry expert with experience in the early stage commercialization of biomedical products. During its course the project is directly training three graduate students in use-inspired research and practical problem-solving through a cross-disciplinary approach that combines materials engineering, cell biology and dental science. The combination of innovative TAMP technology and its potential societal impact has drawn much general student interest, which will be further expanded through more definitive results of this project.