Bioactive agent loaded hydrogel systems for dental tissue engineering applications

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2021-9-07

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Atila, Deniz Hazal

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Use of tissue engineered oral restoration products is currently a popular approach for treating dental defects that adversely affect oral health in ageing populations. Among scaffolds composed of long-lasting porous ceramics and biodegradable natural or synthetic polymers with varying service lives, injectable hydrogels attract attention to regenerate dental pulp due to the capability of filling non-uniform voids such as pulp cavity. In this study, two types of injectable hydrogels were formulized by designing distinct morphologies with the utilization of different biomaterials. Firstly, Tideglusib (Td)-loaded hyaluronic acid hydrogels (HAH) incorporated with Rg1-loaded chitosan microspheres (CSM) were developed for vital pulp regeneration, providing controlled release of Td drug and a ginsenoside Rg1 for matching two basic requirements of pulp; (i) odontoblastic differentiation of human dental pulp stem cells (DPSC) and (ii) vascularization of pulp. Secondly, gelatin methacrylate (GelMA)/thiolated pectin (PecTH) hydrogels (GelMA/PecTH) incorporated with the electrospun core/shell fibers, i.e. melatonin (Mel)-loaded polymethylmethacrylate (PMMA)/Td-loaded silk fibroin (SF) as the core and the shell components respectively, were designed as an alternative injectable hydrogel for vital pulp regeneration, providing controlled release of Td and Mel for inducing proliferation and odontoblastic differentiation of DPSC for a prolonged period. For the first formulation, the expression of the specific genes (COL1A1, ALP, OCN, Axin-2, DSPP, and DMP1) confirmed odontogenic differentiation of DPSC which were incubated with Td-loaded HAH hydrogels incorporated with Rg1-loaded CSM microspheres. Angiogenic potential of the Rg1-containing hydrogel systems among all the other groups were shown on Matrigels in vitro with HUVEC. For the second formulation, cell viability assay showed that DPSC proliferated more in the groups of GelMA/PecTH hydrogels incorporated with PMMA/SF with a Mel/Td ratio of 1/3. ALP activity tests demonstrated that DPSC had the highest odontogenic differentiation level in the hydrogels groups containing PMMA/SF with a Mel/Td ratio of 3/1. Therefore, these novel injectable hydrogels have a potential as candidate biomaterials for vital pulp regeneration.

Subject Keywords

Tideglusib, Hydrogel, Electrospun Fibers, Microspheres, Dental Tissue Engineering

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https://hdl.handle.net/11511/94194

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

D. H. Atila, “Bioactive agent loaded hydrogel systems for dental tissue engineering applications,” Ph.D. - Doctoral Program, Middle East Technical University, 2021.