GSK3 Inhibitor-Induced Dentinogenesis Using a Hydrogel.
Details
Serval ID
serval:BIB_29A7C6989CB5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
GSK3 Inhibitor-Induced Dentinogenesis Using a Hydrogel.
Journal
Journal of dental research
ISSN
1544-0591 (Electronic)
ISSN-L
0022-0345
Publication state
Published
Issued date
01/2022
Peer-reviewed
Oui
Volume
101
Number
1
Pages
46-53
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Small-molecule drugs targeting glycogen synthase kinase 3 (GSK3) as inhibitors of the protein kinase activity are able to stimulate reparative dentine formation. To develop this approach into a viable clinical treatment for exposed pulp lesions, we synthesized a novel, small-molecule noncompetitive adenosine triphosphate (ATP) drug that can be incorporated into a biodegradable hydrogel for placement by syringe into the tooth. This new drug, named NP928, belongs to the thiadiazolidinone (TDZD) family and has equivalent activity to similar drugs of this family such as tideglusib. However, NP928 is more water soluble than other TDZD drugs, making it more suitable for direct delivery into pulp lesions. We have previously reported that biodegradable marine collagen sponges can successfully deliver TDZD drugs to pulp lesions, but this involves in-theater preparation of the material, which is not ideal in a clinical context. To improve surgical handling and delivery, here we incorporated NP928 into a specifically tailored hydrogel that can be placed by syringe into a damaged tooth. This hydrogel is based on biodegradable hyaluronic acid and can be gelled in situ upon dental blue light exposure, similarly to other common dental materials. NP928 released from hyaluronic acid-based hydrogels upregulated Wnt/β-catenin activity in pulp stem cells and fostered reparative dentine formation compared to marine collagen sponges delivering equivalent concentrations of NP928. This drug-hydrogel combination has the potential to be rapidly developed into a therapeutic procedure that is amenable to general dental practice.
Keywords
Dental Pulp, Dentin, Secondary, Dentinogenesis/drug effects, Glycogen Synthase Kinase 3/antagonists & inhibitors, Humans, Hydrogels, Thiadiazoles/pharmacology, Wnt signaling, dental pulp, dentine, mineralization, stem cells, tissue engineering
Pubmed
Web of science
Open Access
Yes
Create date
12/01/2024 10:14
Last modification date
13/01/2024 7:10