Overcoming the Dependence on Animal Models for Osteoarthritis Therapeutics – The Promises and Prospects of In Vitro Models

Abstract

Osteoarthritis (OA) is a musculoskeletal disease characterized by progressive degeneration of osteochondral tissues. Current treatment is restricted to the reduction of pain and loss of function of the joint. To better comprehend the OA pathophysiological conditions, several models are employed, however; there is no consensus on a suitable model. In this review, different in vitro models being developed for possible therapeutic intervention of OA are outlined. Herein, various in vitro OA models starting from 2D model, co-culture model, 3D models, dynamic culture model to advanced technologies-based models such as 3D bioprinting, bioassembly, organoids, and organ-on-chip-based models are discussed with their advantages and disadvantages. Besides, different growth factors, cytokines, and chemicals being utilized for induction of OA condition are reviewed in detail. Furthermore, there is focus on scrutinizing different molecular and possible therapeutic targets for better understanding the mechanisms and OA therapeutics. Finally, the underlying challenges associated with in vitro models are discussed followed by future prospective. Taken together, a comprehensive overview of in vitro OA models, factors to induce OA-like conditions, and intricate molecular targets with the potential to develop personalized osteoarthritis therapeutics in the future with clinical translation is provided.

The Added Value of the “Co” in Co-Culture Systems in Research on Osteoarthritis Pathology and Treatment Development

“…Here, culture conditioned are better controlled yielding in higher reproducibility. Yet, a clear drawback of animal tissue is that joint physiology might differ from human and that physical characteristics such as joint size and cartilage thickness cannot be matched optimally to human OA joint tissue ( Singh et al, 2021 ). Another distinct disadvantage of this approach is that these tissues originate from young and healthy animals, and therefore OA has to be induced in vitro .…”

Stem Cells in Autologous Microfragmented Adipose Tissue: Current Perspectives in Osteoarthritis Disease

“…Some authors have biofabricated human cartilage using adipose tissue deriving from infrapatellar fat succeeding in production of hyaline cartilage on a bio scaffold in order to produce a patient tailored cartilage to replace the injured one [124]. To conclude, this technology can be used to develop in vitro model of osteoarthritis that can be used for further scientific research [125][126][127][128][129][130].…”

Microfluidic Invasion Chemotaxis Platform for 3D Neurovascular Co-Culture

“…Microfluidic setups containing patient-derived cells allow for studying extracellular matrix (ECM) at cellular scales [17,18]. In addition, many inherited diseases involve multiple genetic mutations, requiring various animal models for a single disease [19][20][21][22]. Microfluidics enables the production of systems populated with human cells that recapitulate some aspects of organ functions and can be used to study important molecular or cellular events in a physiologically-relevant construct for exploring the causes of acute or chronic diseases [23].…”