Three-Dimensional Printing of Click Functionalized, Peptide Patterned Scaffolds for Osteochondral Tissue Engineering.

Osteochondral repair remains a significant clinical challenge due to the multiple tissue phenotypes and complex biochemical milieu in the osteochondral unit. To repair osteochondral defects, it is necessary to mimic the gradation between bone and cartilage, which requires spatial patterning of multiple tissue-specific cues. To address this need, we have developed a facile system for the conjugation and patterning of tissue-specific peptides by melt extrusion of peptide-functionalized poly(ε-caprolactone) (PCL). In this study, alkyne-terminated PCL was conjugated to tissue-specific peptides via a mild, aqueous, and Ru(II)-catalyzed click reaction. The PCL-peptide composites were then 3D printed by multimaterial segmented printing to generate user-defined patterning of tissue-specific peptides. To confirm the bioactivity of 3D printed PCL-peptide composites, bone- and cartilage-specific scaffolds were seeded with mesenchymal stem cells and assessed for deposition of tissue-specific extracellular matrix in vitro. PCL-peptide scaffolds successfully promoted osteogenic and chondrogenic matrix deposition, with effects dependent on the identity of conjugated peptide.