Santos Beato, Patricia; (2023) 3D Bioprinting of an in vitro Osteochondral Model for Osteoarthritis Disease Modelling. Doctoral thesis (Eng.D), UCL (University College London).

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Abstract

Osteoarthritis is the most prevalent joint disease globally. There is no cure or a reliable human disease model to understand it further and test new treatments. Developing reliable disease models is key to improving our understanding of these pathologies. This thesis has three main research focuses: 1) investigate the use of self-assembling peptides, Peptigels®, for 3D-bioprinting cartilage in vitro models; 2) use a hydroxyapatite (HA) ink, to 3D-print bone-like in vitro models, 3) combine the developed cartilage and bone-like in vitro models to make osteochondral tissue constructs. Firstly, Peptigels® Alpha 1, 2, and 4 were screened, assessing their rheological, pH, diffusion, and printability properties. Alpha 1 and 4 were chosen to test their chondrogenic potential by 3D-bioprinting. Circular disc structures were 3D-bioprinted with human primary chondrocytes. They were compared to a cell pellet cartilage “gold standard” model. Alpha 1 demonstrated better chondrogenic potential than Alpha 4, inducing chondrogenic marker expression significantly faster than the “gold standard” (p < 0.05). Secondly, an HA ink was used to 3D-print grid structures seeded with Saos-2 cells or human primary osteoblasts (HOBs). These structures promoted osteogenic marker expression in Saos-2 faster than their 2D control (p < 0.05). Finally, these HA structures were combined with Alpha 1. Acellular-HA, Saos-2-seeded HA, and HOBs-seeded HA were tested. Osteogenic and chondrogenic marker expression demonstrated that the HA construct did not compromise the chondrogenic behaviour of Alpha 1. The osteogenic potential of the HA construct was compromised due to the change in the cell culture medium. These osteochondral models demonstrated the expected tissue marker expression, confirming that non-animal-derived human osteochondral tissue models can be developed. Further culture medium composition optimisation and comparison to native osteochondral tissues should be performed. Additional work should focus on inducing osteoarthritis on these constructs and compare them to in vivo samples to have a reliable disease model.

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