Fiber Reinforced Cartilage ECM Functionalized Bioinks for Functional Cartilage Tissue Engineering

Abstract

Focal articular cartilage (AC) defects, if left untreated, can lead to debilitating diseases such as osteoarthritis. While several tissue engineering strategies have been developed to promote cartilage regeneration, it is still challenging to generate functional AC capable of sustaining high load-bearing environments. We developed a new class of cartilage extracellular matrix (cECM)-functionalized alginate bioink for the bioprinting of cartilaginous tissues. The bioinks were 3D-printable, supported mesenchymal stem cell (MSC) viability post-printing and robust chondrogenesis in vitro, with the highest levels of COLLII and ACAN expression observed in bioinks containing the highest concentration of cECM. Enhanced chondrogenesis in cECM-functionalized bioinks was also associated with progression along an endochondral-like pathway, as evident by increases in RUNX2 expression and calcium deposition in vitro. The bioinks loaded with MSCs and TGF-β3 were also found capable of supporting robust chondrogenesis, opening the possibility of using such bioinks for direct ‘print-and-implant’ cartilage repair strategies. Finally, we demonstrated that networks of 3D-printed polycaprolactone fibers with compressive modulus comparable to native AC could be used to mechanically reinforce these bioinks, with no loss in cell viability. It is envisioned that combinations of such biomaterials can be used in multiple-tool biofabrication strategies for the bioprinting of biomimetic cartilaginous implants.