Multifunctional Colloidal Gel for Dentin Formation

用于牙本质形成的多功能胶体凝胶

• 批准号: 10620203
• 负责人: Debanjan Sarkar
• 金额: $ 7.73万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-11 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10620203
• 关键词: Acids; Address; Affect; Anti-Bacterial Agents; Antibacterial Response; Architecture; Area; BMP2 gene; Bacteria; Bacterial Infections; Biochemical; Biocompatible Materials; Biomimetics; Calcium; Carbomer-940; Carboxylic Acids; Cells; Characteristics; Charge; Chronic; Clinical; Colloids; Complex; Data; Defect; Dental; Dental Materials; Dental Pulp; Dental caries; Dentin; Dentin Formation; Dentinogenesis; Edetic Acid; Effectiveness; Endodontics; Endothelium; Engineering; Gel; Generations; Glass; Goals; Growth Factor; In Vitro; Inflammation; Injectable; Iron; Left; Mediating; Minerals; Modality; Modeling; Modification; Morphogenesis; Natural regeneration; Odontoblasts; Outcome; Phase; Plant Resins; Polyurethanes; Property; Regenerative capacity; Residual state; Side; Structure; System; Therapeutic; Therapeutic Intervention; Tissue Engineering; Tissues; Tooth Diseases; Tooth structure; Tubular formation; Up-Regulation; Work; antimicrobial; base; biomaterial compatibility; clinical application; crosslink; dental infection; design; improved; microbial disease; mineralization; novel; oxidation; particle; regeneration potential; regenerative; repaired; response; restoration; restorative material; simulation; stem cell differentiation; stem cells; therapeutically effective

Current treatment modalities for treating dental infection and tooth defects via tertiary reactionary dentinogenesis have limited regenerative capacities. The microenvironment of diseased tooth presents heterogeneous and complex microenvironment due to bacterial contaminations, altered architecture of the residual dentin matrix and reduced functionality of the surviving odontoblasts. Lack of restorative materials which can simultaneously provide antibacterial response and stimulate the residual dentin matrix limits reactionary dentin formation via tertiary dentinogenesis. Use of biomaterial based tissue engineering can address this limitation where the functional materials can simultaneously provide antibacterial response and necessary stimulations to existing odontoblasts to form reactionary dentin. Recently, colloidal gels with tunable mechanomorphology were developed to regulate cellular morphogenesis and preliminary data show that these gels can be engineered to promote reactionary dentin formation. The main goal of this project is to develop a multifunctional colloidal gel which can present antibacterial responses, stimulate the residual dentin to unleash the growth factors and provide a matrix for delivery of exogenous growth factors and mineralization. To achieve these goals, a multifunctional colloidal gel will be designed by associating polyacrylic acid (PA) based bridged colloidal gels with Fe-EDTA (iron-ethylenediaminetetraacetic acid) complex, where Fe forms coordinate bonds with negatively charged PA. The Fe-EDTA component can offer antibacterial character from Fe through Fenton oxidation and EDTA can provide trans-dentinal stimulation to unleash trapped growth factors. The PA based colloidal gel will provide a matrix to deliver exogenous growth factor, TGF-β1 and BMP- 2 as stimulatory factors for reactionary dentinogenesis and template for mineralization during dentinogenesis. Collectively, this design enables synchronization of the essential features which are important for reactionary formation. Therefore, the aims are to (a) develop the multifunctional colloidal gels with these components and characterize their properties, and (b) assess their responses toward reactionary dentin formation with ex vivo models. The outcomes will establish these gels as antimicrobial matrix which will further stimulate the regeneration by presenting growth factors and mineralizable matrix. Thus, by synchronizing these features in a single matrix, this system will address the inflammation and promote dentin matrix via regeneration. These colloidal gels will represent a new class of therapeutically relevant injectable biomaterial for complete dentin regeneration.

当前的治疗方式，用于通过三级反动的治疗牙齿感染和牙齿缺陷 牙齿生成的再生能力有限。患病牙齿的微环境 由于细菌污染而导致的异质和复杂的微环境，改变了结构的改变 残留的牙本质基质和存活的Odontoblasts的功能降低。缺乏恢复材料 可以轻松提供抗菌反应并刺激残留的牙本质基质极限 通过第三次牙本质发生的反动牙本质形成。使用基于生物材料的组织工程可以 解决此限制，功能材料可以简单地提供抗菌反应和 对现有的牙糖细胞形成反动牙本质的必要刺激。最近，具有可调的胶体凝胶 制定了机械形态来调节细胞形态发生，并初步数据表明这些 可以设计凝胶以促进反动牙本质形成。该项目的主要目标是开发 可以呈现抗菌反应的多功能胶体凝胶，刺激残留的牙本释放以释放 生长因子并提供了用于输送外源生长因子和矿化的基质。 为了实现这些目标，将通过关联多丙烯酸（PA）设计多功能胶体凝胶 基于Fe-EDTA（铁乙二胺乙酸）配合物的基于桥接的胶体凝胶，其中形成了Fe 与带负电的PA协调债券。 FE-EDTA组件可以提供抗菌特征 Fe通过芬顿氧化和EDTA可以提供跨牙齿刺激以释放捕获的生长 因素。基于PA的胶体凝胶将提供一个基质，以提供外源生长因子TGF-β1和BMP- 2作为刺激性牙本质生成和模板的刺激因子，用于牙毒发生过程中的矿化。 总的来说，该设计使基本特征同步对反动派很重要 形成。因此，目的是（a）与这些成分以及 表征其特性，（b）评估其对反动牙本质形成的反应 型号。结果将把这些凝胶确定为抗菌基质，这将进一步刺激 通过提出生长因子和可矿化基质来再生。通过将这些功能同步在 单基质，该系统将通过再生来解决炎症并促进牙本质基质。这些 胶体凝胶将代表一类新的治疗性相关注射生物材料，用于完整牙本质 再生。