Patterned, organoid-based cartilaginous implants exhibit zone specific functionality forming osteochondral-like...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Developmental Biology

Background:

• Current tissue engineering methods struggle to create patterned constructs with distinct biological functions for osteochondral defects.
• A modular, developmentally-inspired approach using cartilaginous organoids as building blocks is proposed.

Purpose of the Study:

• To develop a method for creating patterned tissue engineered constructs with distinct zonal functionality.
• To investigate the potential of using iPSC-derived cartilage microtissues and pre-hypertrophic cartilage organoids for osteochondral defect repair.

Main Methods:

• A hierarchical construct was created using human periosteum-derived cells with early, mature, and pre-hypertrophic phenotypes.
• iPSC-derived cartilage microtissues were generated and implanted subcutaneously in nude mice.
• Assembled iPSC-derived cartilage microtissues combined with pre-hypertrophic cartilage organoids were implanted to assess dual-tissue formation.

Main Results:

• Initial constructs formed hybrid tissues, but the non-mineralized part was fibrocartilage-like.
• Assembled iPSC-derived cartilage microtissues formed homogenous cartilaginous tissue.
• Combining iPSC-derived cartilage microtissues with pre-hypertrophic organoids resulted in dual tissues with distinct cartilaginous and bony regions, matching the pre-engineered zonal pattern.

Conclusions:

• The assembly of functional, pre-programmed building blocks enables the creation of complex tissue engineered implants.
• This modular approach allows for embedding zone-specific functionality, offering a promising strategy for treating deep osteochondral defects.