Multifunctional Colloidal Gel for Dentin Formation

用于牙本质形成的多功能胶体凝胶

• 批准号: 10452975
• 负责人: Debanjan Sarkar
• 金额: $ 7.74万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452975
• 关键词: 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.

通过第三反应治疗牙齿感染和牙齿缺损的当前治疗模式 牙本质发生的再生能力有限。患牙微环境呈现 由于细菌污染，微生物的结构改变， 残留的牙本质基质和存活的成牙本质细胞的功能降低。缺乏修复材料 其可同时提供抗菌反应并刺激残余牙本质基质极限 反应性牙本质形成通过三级牙本质发生。使用基于生物材料的组织工程可以 解决了功能材料可以同时提供抗菌响应的这种限制， 对现有成牙本质细胞形成反应性牙本质的必要刺激。最近，具有可调节的 机械形态学被开发来调节细胞形态发生，初步数据表明，这些 凝胶可以被设计成促进反应性牙质形成。该项目的主要目标是开发一个 多功能胶体凝胶，可呈现抗菌反应，刺激残留牙本质释放， 生长因子并提供用于递送外源性生长因子和矿化的基质。 为了实现这些目标，将聚丙烯酸（PA）与聚丙烯酸（PA）结合，设计一种多功能胶体凝胶 含Fe-EDTA（铁-乙二胺四乙酸）络合物的基于桥联的胶体凝胶，其中Fe形成 与带负电荷的PA配位键。Fe-EDTA组分可以提供抗菌特性， Fe通过芬顿氧化和EDTA可以提供跨牙本质刺激以释放被困生长 因素基于PA的胶体凝胶将提供递送外源性生长因子、TGF-β1和BMP-2的基质。 2作为反应性牙本质形成的刺激因子和牙本质形成过程中矿化的模板。 总的来说，这种设计能够实现对反应式应用程序重要的基本功能的同步。 阵因此，目的是（a）开发具有这些组分的多功能胶体凝胶， 表征它们的性质，和（B）评估它们对离体反应性牙本质形成的反应， 模型结果将确立这些凝胶作为抗菌基质，这将进一步刺激 通过呈现生长因子和可矿化基质进行再生。因此，通过将这些特征同步到 单一基质，该系统将解决炎症并通过再生促进牙本质基质。这些 胶体凝胶将代表一种新的治疗相关的可注射生物材料， 再生