Printing cells and co-cultures for osteoarthritis models

Abstract

Osteoarthritis is a multifactorial disease characterised by the degradation of cartilage and bone tissue within the joint. Research into novel therapies is currently limited by the throughput and replicative accuracy of early-stage in vitro disease models. Biofabrication represents an emerging technology which allows for the selective deposition of cells and material in order to create complex cell-laden structures. The aim of this research was to characterise a combination of inkjet and valve-based drop-on-demand printing processes for the construction of osteoarthritis tissue models. An inkjet printing platform was characterised to deposit material at the picolitre-scale. Single cell printing was achieved, with biological analysis confirming that the printing process does not significantly affect cellular viability or function. A valve printing process was applied for the production of cellular aggregates that could be used for both in vitro osteoarthritis research and in vivo therapeutic applications. Reliable jetting performance was demonstrated, enabling material deposition at the nanolitre-scale. Cell printing was achieved across a concentration range of 1-20 million cells per mL, with biological analysis of printed cells revealing no significant effects on viability or function. No discernible impact on aggregate tissue structure was observed as a result of the printing process, confirming its suitability for the manufacture of tissue aggregates. A bioprinted co-culture tissue model comprised of mesenchymal stromal cell and chondrocyte cell types was successfully generated using a 3D insert culture format. Cell proliferation was maintained over a 14 day period, alongside an increase in tissue density and cellular organisation. In combination, this research has demonstrated the suitability of inkjet and valve printing processes to selectively deposit cells. Bioprinted aggregate and insert-based 3D tissue models were validated using the valve printing technique, providing an effective method to scale up the manufacture of in vitro platforms for osteoarthritis research applications.