Multifunctional Colloidal Gel for Dentin Formation

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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.