Mucin-Based Dual Cross-Linkable IPN Hydrogel Bioink for 3D Bioprinting and Cartilage Tissue Engineering

The cartilage possesses limited regenerative capacity, necessitating advanced approaches for its repair. This study introduces a bioink designed for cartilage tissue engineering (TE) by incorporating ionically cross-linkable alginate into the photo-cross-linkable MuMA bioink, resulting in a double cross-linked interpenetrating network (IPN) hydrogel. Additionally, hyaluronic acid (HA), a natural component of cartilage and synovial fluid, was added to enhance the scaffold's properties. HA has been demonstrated to improve cartilage lubrication, regulate inflammation, promote cell proliferation, and support extracellular matrix (ECM) deposition and regeneration, making it valuable for cartilage TE. Comprehensive experiments were conducted to assess morphology, swelling, degradation, mechanical and rheological properties, printability, and biocompatibility. Results indicated that the double cross-linked scaffolds comprising MuMA, alginate, and HA exhibited compressive moduli comparable to native cartilage, unlike single cross-linked variants. The double cross-linking also influenced degradation, water uptake, and porosity, contributing to the scaffold durability and stability for chondrocyte support. Biocompatibility tests with C28/I2 cells demonstrated the cell-supportive and chondrogenic potential of the bioink. This study establishes mucin as a versatile material for specialized cartilage tissue engineering applications.