In-situ handheld 3D Bioprinting for cartilage regeneration

Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ 3D printing is an exciting and innovative bio-fabrication technology that enables the surgeon to deliver tissue- engineering techniques at the time and location of need. We have created a hand- held 3D printing device (Biopen) that allows the simultaneous co-axial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single session surgery. This pilot study assesses the ability of the Biopen to repair a full thickness chondral defect and the early outcomes in cartilage regeneration, and compares these results to other treatments in a large animal model. A standardised critical-sized full thickness chondral defect was created in the weight-bearing surface of the lateral and medial condyles of both femurs of 6 sheep. Each defect was treated with one of the following treatments: (i) hand- held in situ 3D printed bioscaffold using the Biopen (HH group), (ii) pre- constructed bench-based printed bioscaffolds (BB group), (iii) micro-fractures (MF group) or (iv) untreated (Control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bio-printing was performed in all animals without any intra- or post- operative complication. The HH Biopen allowed early cartilage regeneration. Results of this study show that real-time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.