3D bioactive ionic liquid-based architectures: An anti-inflammatory approach for early-stage osteoarthritis

3D bioprinting enables the fabrication of biomimetic cell-laden constructs for cartilage regeneration, of- fering exclusive strategies for precise pharmacological screenings in osteoarthritis (OA). Synovial inflam- mation plays a crucial role in OA’s early stage and progression, characterized by the increased of the syn- ovial pro-inflammatory mediators and cytokines and chondrocyte apoptosis. Therefore, there is an urgent need to develop solutions for effectively managing the primary events associated with OA. To address these issues, a phenolic-based biocompatible ionic liquid approach, combining alginate (ALG), aceman- nan (ACE), and cholinium caffeate (Ch[Caffeate]), was used to produce easily printable bioinks. Through the use of this strategy 3D constructs with good printing resolution and high structural integrity were obtained. The encapsulation of chondrocytes like ATDC5 cells provided structures with good cell distribu- tion, viability, and growth, for up to 14 days. The co-culture of the constructs with THP-1 macrophages proved their ability to block pro-inflammatory cytokines (TNF- αand IL-6) and mediators (GM-CSF), re- leased by the cultured cells. Moreover, incorporating the biocompatible ionic liquid into the system sig- nificantly improved its bioactive performance without compromising its physicochemical features. These findings demonstrate that ALG/ACE/Ch[Caffeate] bioinks have great potential for bioengineering cartilage tissue analogs. Besides, the developed ALG/ACE/Ch[Caffeate] bioinks protected encapsulated chondrocyte- like cells from the effect of the inflammation, assessed by a co-culture system with THP-1 macrophages. These results support the increasing use of Bio-ILs in the biomedical field, particularly for developing 3D bioprinting-based constructs to manage inflammatory-based changes in OA.