Mimicking the Articular Joint with In Vitro Models

Piluso, Susanna; Li, Yang; Abinzano, Florencia; Levato, Riccardo; Teixeira, Liliana S. Moreira; Karperien, Marcel; Leijten, Jeroen; Weeren, P.R. van; Malda, Jos

doi:10.1016/j.tibtech.2019.03.003

Cited by 33 publications

(37 citation statements)

References 92 publications

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“…Collagen fibers, fenestrated blood capillaries and lymph vessels are other structures found in the inner layers of the membrane. The synovial fluid, produced by ultrafiltration of plasma, nourishes the non-irrigated articular cartilage, lubricates and absorbs shock [36,38]. Drug delivery systems with drugs targeting the synovium, like TSG-6 (TNFα gene precursor) or VX-745 (p38 MAPK inhibitor) are active on type B synoviocytes and macrophages, mostly through inflammatory and pain pathways [39,40].…”

Section: Intra-articular Drug Delivery Systems and Interactions With mentioning

confidence: 99%

Osteoarthritis In Vitro Models: Applications and Implications in Development of Intra-Articular Drug Delivery Systems

2021

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Osteoarthritis (OA) is a complex multi-target disease with an unmet medical need for the development of therapies that slow and potentially revert disease progression. Intra-articular (IA) delivery has seen a surge in osteoarthritis research in recent years. As local administration of molecules, this represents a way to circumvent systemic drug delivery struggles. When developing intra-articular formulations, the main goals are a sustained and controlled release of therapeutic drug doses, taking into account carrier choice, drug molecule, and articular joint tissue target. Therefore, the selection of models is critical when developing local administration formulation in terms of accurate outcome assessment, target and off-target effects and relevant translation to in vivo. The current review highlights the applications of OA in vitro models in the development of IA formulation by means of exploring their advantages and disadvantages. In vitro models are essential in studies of OA molecular pathways, understanding drug and target interactions, assessing cytotoxicity of carriers and drug molecules, and predicting in vivo behaviors. However, further understanding of molecular and tissue-specific intricacies of cellular models for 2D and 3D needs improvement to accurately portray in vivo conditions.

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Section: Intra-articular Drug Delivery Systems and Interactions With mentioning

confidence: 99%

Osteoarthritis In Vitro Models: Applications and Implications in Development of Intra-Articular Drug Delivery Systems

2021

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“…Microfluidic systems may be a promising alternative as they offer the great benefit of recreating dynamic flow conditions, biochemical, and mechanical stimuli in a closer way than classical culture methods. Thanks to 3D manufacturing, microfluidics may propose multitissue systems with nuanced and complex biological responses [ 20 , 204 , 205 ]. Along this line, Tuan, R.S.…”

Section: Microfluidics As Research Systems In Oa: Their Pros and Cons In Regenerative Medicinementioning

confidence: 99%

“…Although this system shows several advantages, further improvements are still necessary to recreating typical immune-mediated reactions during OA. Despite the advances in this field, several issues still exist [ 205 ]. Manufacturing ECM has to consider the establishment of various structures, stiffness, flow rates, and cell sources mimicking joint architecture to develop a reliable multitissue organ ( Table 3 ).…”

Section: Microfluidics As Research Systems In Oa: Their Pros and Cons In Regenerative Medicinementioning

confidence: 99%

“…When referring to 3D models with scaffolds, their selection covers great importance, since findings vary greatly based on their nature and architecture. Indeed, bioreactors and microfluidics systems also contributed to improving current methodological approaches by introducing specific biochemical and mechanical issues in miniaturized systems [ 204 , 205 , 206 , 207 , 208 ]. Along this line, scientists designed and developed accurate in vitro approaches to model the multiple interactions among cells from joint tissues.…”

Section: Conclusion and Future Research Outlookmentioning

confidence: 99%

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A Roadmap of In Vitro Models in Osteoarthritis: A Focus on Their Biological Relevance in Regenerative Medicine

Bartolotti

Roseti

Petretta

et al. 2021

JCM

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Osteoarthritis (OA) is a multifaceted musculoskeletal disorder, with a high prevalence worldwide. Articular cartilage and synovial membrane are among the main biological targets in the OA microenvironment. Gaining more knowledge on the accuracy of preclinical in vitro OA models could open innovative avenues in regenerative medicine to bridge major gaps, especially in translation from animals to humans. Our methodological approach entailed searches on Scopus, the Web of Science Core Collection, and EMBASE databases to select the most relevant preclinical in vitro models for studying OA. Predicting the biological response of regenerative strategies requires developing relevant preclinical models able to mimic the OA milieu influencing tissue responses and organ complexity. In this light, standard 2D culture models lack critical properties beyond cell biology, while animal models suffer from several limitations due to species differences. In the literature, most of the in vitro models only recapitulate a tissue compartment, by providing fragmented results. Biotechnological advances may enable scientists to generate new in vitro models that combine easy manipulation and organ complexity. Here, we review the state-of-the-art of preclinical in vitro models in OA and outline how the different preclinical systems (inflammatory/biomechanical/microfluidic models) may be valid tools in regenerative medicine, describing their pros and cons. We then discuss the prospects of specific and combinatorial models to predict biological responses following regenerative approaches focusing on mesenchymal stromal cells (MSCs)-based therapies to reduce animal testing.

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“…16,[18][19][20][21] Despite recent advances in in vitro models for the articular joint, no organ-on-a-chip system emulating functional 3D tissue architecture of the synovium has been reported so far. 22 From an anatomical viewpoint, the healthy synovium is a highly organized structure that resides between the joint cavity and the fibrous joint capsule and consist of two separate layers: a lining layer formed by condensed cells, up to four cell layers thick, and a loosely organized sublining layer composed of extracellular matrix, scattered fibroblasts, macrophages, mast cells, nerves, blood vessels, and lymphatics. 23 In other words, the sublining layer as loose connective tissue forms the microanatomic base of the synovial lining where fibroblast-like synoviocytes form a continuous network of compacted cells.…”

Section: Introductionmentioning

confidence: 99%

Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing

et al. 2020

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Mimicking the Articular Joint with In Vitro Models

Cited by 33 publications

References 92 publications

Osteoarthritis In Vitro Models: Applications and Implications in Development of Intra-Articular Drug Delivery Systems

Osteoarthritis In Vitro Models: Applications and Implications in Development of Intra-Articular Drug Delivery Systems

A Roadmap of In Vitro Models in Osteoarthritis: A Focus on Their Biological Relevance in Regenerative Medicine

Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing

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