Enhancing bioactivity of 3D-printed porous scaffolds with self-assembling peptide hydrogels for cartilage tissue engineering

BACKGROUND: Cartilage repair is challenging due to the tissue's limited regenerative capacity. Synthetic 3D-printed scaffolds provide essential structural support, but typically lack the bioactivity needed for cell integration. A promising approach combines 3D-printed porous scaffolds filled with self-assembling peptide hydrogels, which serve as nanofiber scaffolds inside the macropores of the structural scaffold, creating a hybrid structure. METHODS: The selection strategy for the 3D printing of the synthetic scaffolds was driven by two distinct cross-linking processes: a vinyl-ester based thiol-ene photopolymer crosslinked via free radical polymerization and printed with digital light processing, resulting in a stiff mechanical network and polydimethylsiloxane, namely AMSil™ 20503-50 from the AMSil™ 20,503 series, printed via liquid deposition modeling and crosslinked through polyaddition, which yields flexible scaffolds capable of adapting to dynamic mechanical environments. These properties make them suitable for load-bearing applications where structural integrity is paramount. Both 3D-printed scaffold types, characterized by interconnected macropores ranging from 0.8 to 1.2 mm, were augmented with a peptide hydrogel scaffold, such as RADA16 and IEIK13, that self-assembles inside the macropores to create a nanofiber network mimicking the extracellular matrix and enhancing bioactivity. RESULTS: The hybrid structure, combining the macropores of a structural 3D-printed scaffold and the nanofiber network of the peptide hydrogel scaffold improved cell adhesion, proliferation, and differentiation. Comparative analysis showed that, while both RADA16 and IEIK13 hydrogels enhanced cell integration within the macropores, RADA16 was especially effective in supporting cartilage-like ECM formation. CONCLUSIONS: The creation of a hybrid scaffold with hierarchical porosity-integrating the structural macropores of a synthetic 3D-printed scaffold with the bioactive nanofiber network of a peptide hydrogel-addresses the limitations of purely structural scaffolds. The hybrid approach not only enhances fast and accessible scaffold fabrication but also accelerates the development of functional scaffolds.