Multifunctional Colloidal Gel for Dentin Formation

用于牙本质形成的多功能胶体凝胶

基本信息

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
项目类别：
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

项目摘要

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.

目前通过三级反应治疗牙齿感染和牙齿缺陷的治疗方式牙本质发生的再生能力有限。由于细菌污染，微环境异质且复杂，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。它可以同时提供抗菌反应并刺激残余牙本质基质极限使用基于生物材料的组织工程可以通过三级牙本质形成反应性牙本质。解决这一限制，功能材料可以同时提供抗菌反应和对现有成牙本质细胞形成反应性牙本质的必要刺激最近出现了具有可调性的胶体凝胶。机械形态学的发展是为了调节细胞形态发生，初步数据表明这些可以设计凝胶来促进反应性牙本质的形成。该项目的主要目标是开发一种凝胶。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，将通过缔合聚丙烯酸（PA）来设计多功能胶体凝胶基于 Fe-EDTA（铁-乙二胺四乙酸）复合物的桥联胶体凝胶，其中 Fe 形成 Fe-EDTA 成分与带负电荷的 PA 形成配位键，可提供抗菌特性。 Fe 通过芬顿氧化和 EDTA 可以提供跨牙本质刺激，以释放被困的生长基于 PA 的胶体凝胶将提供基质来输送外源生长因子、TGF-β1 和 BMP-。 2 作为牙本质发生反应的刺激因子和牙本质发生过程中矿化的模板。总的来说，这种设计能够实现对反动重要的基本特征的同步因此，目标是（a）开发具有这些成分的多功能胶体凝胶和表征它们的特性，并（b）评估它们对离体反应性牙本质形成的反应模型的结果将把这些凝胶建立为抗菌基质，这将进一步刺激通过呈现生长因子和可矿化基质来实现再生，因此，通过将这些特征同步化。单一基质，该系统将解决炎症并通过再生促进牙本质基质。胶体凝胶将代表一类新型治疗相关的完整牙本质可注射生物材料再生。