Fungal‐Derived Chitosan‐Based Bioinks Enable Multifunctional Musculoskeletal Tissue Engineering via Enhanced Bioactivity

ABSTRACT

Engineering bioinks that combine mechanical robustness with microenvironmental regulation remains a challenge in musculoskeletal tissue engineering. Collagen‐based bioinks provide intrinsic bioactivity but have limited structural stability and antibacterial and redox‐regulatory functions. Crustacean‐derived chitosan (C‐CS) can address these limitations, but concerns regarding allergenicity and inconsistent immunomodulation remain. Here, we introduce mushroom‐derived chitosan (M‐CS), a fungal‐derived polysaccharide with distinct compositional and physicochemical characteristics, as a multifunctional component enabling simultaneous physicochemical reinforcement and bioactive regulation. Under physiologically relevant conditions, M‐CS exhibits an atypical thermorheological response that enables controlled printing while providing antibacterial and ROS‐modulating properties. Incorporating M‐CS into a collagen matrix produced composite bioinks (collagen 3 wt%, M‐CS 3 wt%, hydroxyapatite 20 wt%) that combine structural reinforcement with bioactive functionality for bone tissue engineering. Particularly, the unique compositional and physicochemical features of M‐CS, including its naturally associated β‐glucan structures, collectively contribute to enhanced cell–matrix interactions and redox regulation, supporting enhanced osteogenic and angiogenic responses compared to collagen/C‐CS/HA and collagen/HA controls. Reduced intracellular ROS levels further establish a pro‐regenerative niche via redox‐sensitive signaling. Moreover, M‐CS/collagen constructs promote robust tenogenic differentiation of human adipose stem cells, demonstrating dual functionality for musculoskeletal interface regeneration.