Amino acid-grafted and N-acylated chitosan thiomers: Construction of 3D bio-scaffolds for potential cartilage repair applications

Abstract

In this work novel three-dimensional (3D) scaffolds were developed with chitosan thiomer derivatives for potential soft tissue repair applications. Amino acid-grafted chitosan (cysteine, CHICys) and N-acylated chitosan (11-mercaptoundecanoic acid, CHIMerc) derivatives were synthesized by covalent coupling reaction and hydrogel scaffolds were produced by freeze-drying process. They were comprehensively characterized by swelling and degradation behaviors, NMR, FTIR and Raman spectroscopy, SEM and X-ray microcomputed tomography. The results demonstrated the synthesis of chitosan thiomers with distinct degree of thiol substitution (CHICys=5% and CHIMerc=26%), producing highly porous scaffolds (porosity >80%) with hierarchical interconnected 3D pore structures. Additionally, their physicochemical properties and architectural features were significantly tuned by the thiol-modifier, evidenced by the swelling degrees ranging from approximately 2300% (CHICys) to 1800% (CHIMerc) and chemical stability against degradation. Moreover, they exhibited cytocompatibility based on in vitro bioassays, which hold promise as suitable platform in soft tissue engineering applications.