A dual functional chondro-inductive chitosan thermogel with high shear modulus and sustained drug release for cartilage tissue engineering

Dorsa Dehghan-Baniani; Babak Mehrjou; Dong Wang; Reza Bagheri; Atefeh Solouk; Paul K Chu; Hongkai Wu

doi:10.1016/j.ijbiomac.2022.02.115

A dual functional chondro-inductive chitosan thermogel with high shear modulus and sustained drug release for cartilage tissue engineering

Int J Biol Macromol. 2022 Apr 30:205:638-650. doi: 10.1016/j.ijbiomac.2022.02.115. Epub 2022 Feb 23.

Authors

Dorsa Dehghan-Baniani¹, Babak Mehrjou², Dong Wang³, Reza Bagheri⁴, Atefeh Solouk⁵, Paul K Chu², Hongkai Wu⁶

Affiliations

¹ Department of Chemical and Biological Engineering, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Hong Kong, China; Polymeric Materials Research Group, Department of Materials Science and Engineering, Sharif University of Technology, Tehran, P.O. Box 11155-9466, Iran.
² Department of Physics, Department of Materials Science and Engineering, Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
³ Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China.
⁴ Polymeric Materials Research Group, Department of Materials Science and Engineering, Sharif University of Technology, Tehran, P.O. Box 11155-9466, Iran.
⁵ Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
⁶ Department of Chemical and Biological Engineering, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Hong Kong, China; Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: chhkwu@ust.hk.

PMID: 35217083
DOI: 10.1016/j.ijbiomac.2022.02.115

Abstract

We report a chitosan-based nanocomposite thermogel with superior shear modulus resembling that of cartilage and dual pro-chondrogenic and anti-inflammatory functions. Two therapeutic agents, kartogenin (KGN) and diclofenac sodium (DS), are employed to promote chondrogenesis of stem cells and suppress inflammation, respectively. To extend the release time in a controlled manner, KGN is encapsulated in the uniform-sized starch microspheres and DS is loaded into the halloysite nanotubes. Both drug carriers are doped into the maleimide-modified chitosan hydrogel to produce a shear modulus of 167 ± 5 kPa that is comparable to that of articular cartilage (50-250 kPa). Owing to the hydrogel injectability and relatively suitable gelation time (5 ± 0.5 min) at 37 °C, this system potentially constitutes a manageable platform for clinical practice. Moreover, sustained linear drug release for over a month boosts chondro-differentiation of stem cells to eliminate the necessity for multiple administrations. Considering virtues such as thermogel strength and ability to co-deliver anti-inflammatory and chondro-inductive biomolecules continuously, the materials and strategy have promising potential in functional cartilage tissue engineering.

Keywords: Cartilage tissue engineering; Chitosan hydrogel; Kartogenin; Starch microspheres.

MeSH terms

Cartilage, Articular*
Cell Differentiation
Chitosan*
Chondrogenesis
Drug Liberation
Hydrogels
Mesenchymal Stem Cells*
Tissue Engineering

Substances

Hydrogels
Chitosan