A 6-bromoindirubin-3'-oxime incorporated chitosan-based hydrogel scaffold for potential osteogenic differentiation: Investigation of material properties in vitro

Celine J Agnes; Monzur Murshed; Adrien Takada; Bettina M Willie; Maryam Tabrizian

doi:10.1016/j.ijbiomac.2022.12.130

A 6-bromoindirubin-3'-oxime incorporated chitosan-based hydrogel scaffold for potential osteogenic differentiation: Investigation of material properties in vitro

Int J Biol Macromol. 2023 Feb 1:227:71-82. doi: 10.1016/j.ijbiomac.2022.12.130. Epub 2022 Dec 17.

Authors

Celine J Agnes¹, Monzur Murshed², Adrien Takada³, Bettina M Willie⁴, Maryam Tabrizian⁵

Affiliations

¹ Department of Biomedical Engineering, McGill University, Montreal, QC, Canada. Electronic address: celine.agnes@mail.mcgill.ca.
² Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada; Shriners Hospital for Children, Montreal, QC, Canada. Electronic address: monzur.murshed@mcgill.ca.
³ Institute of Parasitology, McGill University, Montreal, QC, Canada. Electronic address: adrien.takada@mail.mcgill.ca.
⁴ Department of Biomedical Engineering, McGill University, Montreal, QC, Canada; Shriners Hospital for Children, Montreal, QC, Canada; Department of Pediatric Surgery, McGill University, Montreal, QC, Canada. Electronic address: bwillie@shriners.mcgill.ca.
⁵ Department of Biomedical Engineering, McGill University, Montreal, QC, Canada; Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada. Electronic address: maryam.tabrizian@mcgill.ca.

PMID: 36535349
DOI: 10.1016/j.ijbiomac.2022.12.130

Abstract

Effective treatments for critical size bone defects remain challenging. 6-Bromoindirubin-3'-Oxime (BIO), a glycogen synthase kinase 3β inhibitor, is a promising alternative for treatment of these defects since it aids in promoting osteogenic differentiation. In this study, BIO is incorporated into a new formulation of the guanosine diphosphate cross-linked chitosan scaffold to promote osteogenic differentiation. BIO incorporation was confirmed with ¹³C NMR through a novel concentration dependent peak around 41 ppm. The rapid gelation rate was maintained along with the internal structure's stability. The 10 μM BIO dose supported the control scaffold's microstructure demonstrating a suitable porosity and a low closed pore percentage. While pore sizes of BIO incorporated scaffolds were slightly smaller, pore heterogeneity was maintained. A proof-of-concept study with C2C12 cells suggested a dose-dependent response of BIO on early stages of osteogenic differentiation within the scaffold. These results support future work to examine BIO's role on osteogenic differentiation and biomineralization of encapsulated cells in the scaffold for bone regeneration.

Keywords: 6-Bromoindirubin-3′-oxime; Bone tissue engineering; Chitosan scaffolds; Guanosine diphosphate.

MeSH terms

Cell Differentiation
Chitosan* / chemistry
Hydrogels / pharmacology
Osteogenesis*
Porosity
Tissue Engineering
Tissue Scaffolds / chemistry

Substances

Chitosan
6-bromoindirubin-3'-oxime
Hydrogels