Patterned, organoid-based cartilaginous implants exhibit zone specific functionality forming osteochondral-like tissues in vivo

Tissue engineered constructs have the potential to respond unmet medical need of treating deep osteochondral defects. However, current tissue engineering strategies struggle in attempt create patterned with biologically distinct functionality. In this work, a developmentally-inspired modular approach is proposed, whereby cartilaginous organoids are used as living building blocks. First, hierarchical construct was created, composed three layers intermediates derived from human periosteum-derived cells: (i) early (SOX9), (ii) mature (COL2) and (iii) (pre)hypertrophic (IHH, COLX) phenotype. Subcutaneous implantation nude mice generated hybrid containing one mineralized non-mineralized part. part represented by collagen type I positive fibrocartilage-like tissue. To engineer more stable articular cartilage part, iPSC-derived microtissues (SOX9, COL2; IHH neg) were generated. assembled resulted homogenous for II but negative osteocalcin. Finally, combination pre-hypertrophic could form dual tissues consisting i) safranin O ii) bony osteocalcin region upon subcutaneous implantation, corresponding pre-engineered zonal pattern. The assembly functional blocks, presented opens possibilities production complex implants embedding zone-specific functionality through use pre-programmed