Biomimetics for Dentin Regeneration

牙本质再生仿生学

• 批准号: 6645750
• 负责人: R B Rutherford
• 金额: $ 10万
• 依托单位: DENTIGENIX
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6645750
• 关键词: angiogenesis factor; bioengineering /biomedical engineering; biological signal transduction; biomaterial development /preparation; biomimetics; biotechnology; cell differentiation; dental disorder; dental materials; dental pulp; dentin; dentinogenesis; ferrets; odontoblasts; polymers; pulp disorder; restorative dentistry; root canal therapy; stem cells; technology /technique development; tissue engineering

DESCRIPTION: This project seeks to develop a commercially viable substitute therapy for existing vital pulp therapy, root canal, root repair and apexification procedures. The proposed new therapy is based on novel developments in synthetic polymers for tissue engineering. New methods of polymerization yield fibers or sheets of poly (acids) with controllably-sized interconnecting pores. Additionally biologically active signaling molecules such as morphogens, growth or angiogenic factors and/or a thin layer of carbonated hydroxyapatite crystals and/or cells can be added. These new scaffolds have been demonstrated to serve multiple functions including direct stimulation of bone formation (mineralized version) and controlled release of signaling molecules from mineralized or non-mineralized scaffolds. Herein we propose to determine the capacity of this new material to induce reparative dentinogenesis in vitro and in vivo models of odontoblast differentiation and reparative dentin formation. Mineralized and non-mineralized scaffolds will be tested with and without allogeneic stem cells cultured from dental pulp and gingiva. The rationale for this study derives from our data that experimental protein and ex vivo gene therapies induce both bone and dentin regeneration. Hence it is deemed likely that a simpler approach using a material without additional biological agents might also induce reparative dentinogenesis. AIIogeneic pulp and gingival cells, isolated using methods demonstrated to produce "stem" cells, attached to the mineralized scaffold will be compared to the "neat" scaffold. These experiments will employ our published model of reversible pulpitis induced in adult ferret teeth. If successful these experiments could lead to efficacy tests in non-human primate models of reparative dentinogenesis (Phase II), human clinical trials and commercialization.

描述：该项目旨在开发一种商业上可行的替代疗法，以替代现有的活髓治疗、根管治疗、牙根修复和根尖切除术。拟议的新疗法基于组织工程合成聚合物的新发展。新的聚合方法可产生具有可控尺寸的互连孔的聚酸纤维或片材。另外，可以添加生物活性信号分子，例如形态发生素、生长或血管生成因子和/或碳酸羟基磷灰石晶体和/或细胞的薄层。这些新支架已被证明具有多种功能，包括直接刺激骨形成（矿化版本）以及从矿化或非矿化支架中控制释放信号分子。在此，我们建议确定这种新材料在成牙本质细胞分化和修复性牙本质形成的体外和体内模型中诱导修复性牙本质发生的能力。将使用或不使用从牙髓和牙龈培养的同种异体干细胞来测试矿化和非矿化支架。这项研究的基本原理源自我们的数据，即实验蛋白质和离体基因疗法可诱导骨和牙本质再生。因此，使用不含额外生物制剂的材料的更简单方法也可能诱导修复性牙本质发生。使用经证实可产生“干”细胞的方法分离的异体牙髓和牙龈细胞附着在矿化支架上，将与“纯”支架进行比较。这些实验将采用我们发表的成年雪貂牙齿诱发的可逆性牙髓炎模型。如果成功，这些实验可能会在修复性牙本质发生的非人类灵长类动物模型（第二阶段）、人体临床试验和商业化中进行功效测试。