Conjugation of Proangiogenic Peptide to Enhance a Soft Tissue Bioink

Acellular methods are needed to vascularize 3D-printed tissue-engineered constructs for faster clinical translation. One method is to create bioactive materials that encourage migration and network formation of a patient's own cells. This study utilizes QK peptide, which replicates a binding sequence of vascular endothelial growth factor. This peptide has previously shown to maintain bioactivity when modified with an acrylate group and covalently bound to gelatin methacrylate (GelMA). However, this binding interferes with the crosslinking of the hydrogel matrix, requiring characterization of the modified material. We investigated how binding QK peptide impacts GelMA crosslinking and material properties. A factorial design was employed to investigate the relationships between GelMA concentration, GelMA degree of substitution, and QK peptide concentration. These experiments were used to inform a rheology study, where the impact of QK peptide on crosslinking was investigated over a range of photocrosslinking times. We then investigated the printability of QK-GelMA bioink using rheology and a filament collapse test. The bioactivity induced by the peptide on the hydrogel surface was evaluated using endothelial cell network formation. QK peptide impacted key GelMA characteristics, including swelling behavior, mesh size, and storage modulus, potentially through inhibition of temperature-induced chain entanglement. While bound QK peptide impacts GelMA bioink at the nanoscale, QK-GelMA bioinks maintain high print fidelity and increase endothelial network formation on the surface of the hydrogel. The addition of QK peptide increases the vascularization potential of 3D-printed tissue-engineered constructs.