Nanoenabled Immunomodulatory Scaffolds for Cartilage Tissue Engineering

Articular cartilage regeneration is a challenge in tissue engineering. Although diverse materials have been developed for this purpose, cartilage regeneration remains suboptimal. The integration of nanomaterials into 3D network materials holds great potential in the improvement of key mechanical properties, particularly important for osteochondral replacement scaffolds and even to function as carriers for disease-modifying drugs or other regulatory signals. In this study, a simple yet effective cell-free nanoenabled Col-PLA scaffold specially designed to enhance cartilage regeneration and modulate inflammatory response is proposed, by incorporating poly(lactic-co-glycolic acid) (PLGA) ibuprofen nanoparticles (NPs) into a collagen/polylactide (Col-PLA) matrix. The developed nanoenabled scaffold successfully decreases IL-1 beta release and leads to primary human chondrocytes survival, ultimately restoring extracellular matrix (ECM) production under inflammatory conditions. The nanoenabled Col-PLA scaffolds secretome effectively decreases macrophage invasion in vitro, as well as neutrophil infiltration and inflammatory mediators', namely the complement component C5/C5a, C-reactive protein, IL-1 beta, MMP9, CCL20, and CXCL1/KC production in vivo in a rodent air-pouch model. Overall, the established nanoenabled scaffold has the potential to support chondrogenesis as well as modulate inflammatory response, overcoming the limitations of traditional tissue engineering strategies. A 3D scaffold composed of poly(lactic-co-glycolic acid)-ibuprofen(PLGA-IBU) nanoparticles (NPs)/collagen (Col)/polylactide (PLA) (nanoenabled Col-PLA scaffold), with proven immunomodulatory capabilities is presented. The resulting material offers the right structure for chondrocytes to proliferate and produce cartilage-related extracellular matrix (ECM), while decreases the release of IL-1 beta. This provides a potential solution to overcome the lack of efficient tissue engineering strategies for cartilage regeneration. image