3D printing multiphasic osteochondral tissue constructs with nano to micro features via PCL based bioink

Abstract

Osteochondral tissue has a complex graded structure where biological, physiological, and mechanical properties vary significantly over the full thickness spanning the subchondral bone region beneath the joint surface to the hyaline cartilage region at the joint surface. This presents a significant challenge for tissue-engineered structures addressing osteochondral defects. Advanced bioinks, together with 3D bioprinters, may present a unique solution to this problem. The objective of this research is to apply innovative bioinks, and integrate fused deposition modeling (FDM) 3D printing with a casting technique to fabricate novel osteochondral tissue constructs for improved bone marrow human mesenchymal stem cell (hMSC) functions. Specifically, a multiphasic construct with different layer geometries was designed. A polycaprolactone (PCL) based shape memory material which is comprised of polycaprolactone-triol, castor oil, and poly(hexamethylene diisocyanate) was used as the osteochondral matrix material for the first time. Nanocrystalline hydroxyapatite (nHA) was synthesized and printed into the subchondral bone layers and chondrogenic growth factors were fabricated into the cartilage layer. The results show that the 3D printed constructs with nHA and bioactive cues have improved mechanical properties and enhanced hMSC adhesion, growth, and differentiation. This study indicates that both mechanical properties and cell performance can be easily manipulated through the bioink and the investment casting process to achieve a spatially appropriate osteogenic and chondrogenic response in engineered osteochondral constructs.