Abstract
Recent improvements within the fields of high-throughput screening and 3D tissue culture have provided the possibility of developing in vitro micro-tissue models that can be used to study diseases and screen potential new therapies. This paper reports a proof-of-concept study on the use of microvalve-based bioprinting to create laminar MSC-chondrocyte co-cultures to investigate whether the use of MSCs in ACI procedures would stimulate enhanced ECM production by chondrocytes. Microvalve-based bioprinting uses small-scale solenoid valves (microvalves) to deposit cells suspended in media in a consistent and repeatable manner. In this case, MSCs and chondrocytes have been sequentially printed into an insert-based transwell system in order to create a laminar co-culture, with variations in the ratios of the cell types used to investigate the potential for MSCs to stimulate ECM production. Histological and indirect immunofluorescence staining revealed the formation of dense tissue structures within the chondrocyte and MSC-chondrocyte cell co-cultures, alongside the establishment of a proliferative region at the base of the tissue. No stimulatory or inhibitory effect in terms of ECM production was observed through the introduction of MSCs, although the potential for an immunomodulatory benefit remains. This study, therefore, provides a novel method to enable the scalable production of therapeutically relevant micro-tissue models that can be used for in vitro research to optimise ACI procedures.
Highlights
Previstudies have explored the application of bioprinting technologies such as microvalve ous studies have explored the application of bioprinting technologies such as microvalve printing printingfor forthe theconstruction constructionof ofmicro-tissue micro-tissuemodels
From day 3 to 14, cells undergoing nuclear blebbing transitioned from being evenly dispersed within the tissue to being localised on the upper surface region of the co-culture. These results indicate a potential organisational response within both cell populations when co-cultured, supporting previous studies observing a relationship between mesenchymal stromal cell (MSC) and chondrocyte co-cultures when compared to monocultures of each cell type [53,54]
Our findings demonstrate that microvalve bioprinting can be used to reliably print MSC and chondrocyte cell types in order to generate insert-based co-cultures
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Osteoarthritis is a chronic disease of the articular joint that results in the progressive degradation of cartilage and bone tissue as a consequence of a combination of pathophysiological mechanisms. Estimates of the impact of osteoarthritis on the global population calculated that in 2010 the disease was responsible for approximately 17 million years lived with disability, characterised by an increase of 64% since 1990 [1]. Current treatment strategies range from the application of holistic and self-management approaches to pharmacological therapies, with surgical techniques such as mosaicplasty or total knee replacement considered as the disease progresses [2]
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