A human joint-on-a-chip as alternative to animal models in osteoarthritis

Rothbauer, Mario; Schobesberger, Silvia; Byrne, Ruth A.; Kiener, Hans P.; Tögel, Stefan; Ertl, Peter

doi:10.1016/j.joca.2020.02.135

Cited by 4 publications

(2 citation statements)

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“…However, 3D cultures are either effortful to maintain or, in the case of joint-on-a-chip, not yet commercially available. Therefore, rapid, agile research and development of regenerative therapeutics for cartilage regeneration is limited to a certain extent [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

A Novel Method Facilitating the Simple and Low-Cost Preparation of Human Osteochondral Slice Explants for Large-Scale Native Tissue Analysis

Spinnen

Shopperly

Rendenbach

et al. 2021

IJMS

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For in vitro modeling of human joints, osteochondral explants represent an acceptable compromise between conventional cell culture and animal models. However, the scarcity of native human joint tissue poses a challenge for experiments requiring high numbers of samples and makes the method rather unsuitable for toxicity analyses and dosing studies. To scale their application, we developed a novel method that allows the preparation of up to 100 explant cultures from a single human sample with a simple setup. Explants were cultured for 21 days, stimulated with TNF-α or TGF-β3, and analyzed for cell viability, gene expression and histological changes. Tissue cell viability remained stable at >90% for three weeks. Proteoglycan levels and gene expression of COL2A1, ACAN and COMP were maintained for 14 days before decreasing. TNF-α and TGF-β3 caused dose-dependent changes in cartilage marker gene expression as early as 7 days. Histologically, cultures under TNF-α stimulation showed a 32% reduction in proteoglycans, detachment of collagen fibers and cell swelling after 7 days. In conclusion, thin osteochondral slice cultures behaved analogously to conventional punch explants despite cell stress exerted during fabrication. In pharmacological testing, both the shorter diffusion distance and the lack of need for serum in the culture suggest a positive effect on sensitivity. The ease of fabrication and the scalability of the sample number make this manufacturing method a promising platform for large-scale preclinical testing in joint research.

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Section: Introductionmentioning

confidence: 99%

A Novel Method Facilitating the Simple and Low-Cost Preparation of Human Osteochondral Slice Explants for Large-Scale Native Tissue Analysis

Spinnen

Shopperly

Rendenbach

et al. 2021

IJMS

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“…These features provide a high physiological relevance platform that, in combination with the high-throughput set-up and analysis potential, make for extremely promising platforms for preclinical testing. [85,91] These OoC have been developed to study a wide range of organs and tissues such as liver, [92] lung, [93,94] intestine, [95] kidney, [96,97] the blood brain barrier, [98,99] articular joint tissues, [100,101] as well as vascular structures. [102,103] Naturally, the study of single tissues or organs when it comes to evaluating the systemic effect of drugs in the drug discovery pipeline is a rather reductive approach, so progress in the MPS field seeks to incorporate this inter-organ communication through devices known as human multi-organ-on-a-chip (multi-OoC), which are currently a major focus of in vitro model research.…”

Section: Biofabricated Modelsmentioning

confidence: 99%

Crafting Tissue Complexity

Núñez Bernal

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The global rise in life expectancy is accompanied by an increasing prevalence of chronic diseases, posing economic burdens and impacting patients' well-being. This surge in disease incidence challenges the drug discovery pipeline, calling for the adaptation of its rules and regulations to reduce the ever-increasing failure rates of new drugs. The staggering growth of the pharmaceutical industry in the last decades, and the high expenditure required to bring new drugs to the market is set to become an unsustainable issue in the coming years. Recently, far more attention has been focused on the preclinical phase of the pipeline, where drug evaluation culminates in animal testing, the current gold standard to ensure drug safety and efficacy before human trials. A consensus on the need for more complex and predictive human disease models has emerged and become a priority for scientists and policy makers in the past decade. Biofabrication, an emerging technology-driven field, has gained prominence in biomedical research for developing advanced in vitro models. Biofabrication is “the automated generation of biologically functional products with structural organization from living cells, bioactive molecules, biomaterials, cell aggregates such as micro-tissues, or hybrid cell-material constructs, through Bioprinting or Bioassembly and subsequent tissue maturation processes”. The last decades have seen the rapid development new bioprinting modalities, opening the door to the development of architecturally complex in vitro platforms where multi-cellular and multi-material structures can be more easily created. Considering the need for more complex preclinical models to bridge the translational gap between 2D in vitro models, animal testing and clinical trials, the overarching aim of this thesis was “to develop new biofabrication approaches, encompassing 3D bioprinting technologies, powerful biological building blocks, and smart biomaterials, that facilitate the development of advanced human in vitro models with native tissue-like functionality”. This research has introduced significant advancements within the field of biofabrication for the generation of human in vitro models. Through a comprehensive exploration that tackled challenges related to fundamental bioprinting principles, the biological intricacies, and the biochemical and material property requirements of bioprinted structures to better recapitulate native tissues, the developments described here have expanded the toolkit of biofabrication approaches. By introducing novel technologies, like the pioneering, layerless volumetric bioprinting strategy, and synergizing new and existing printing approaches to harness their unique advantages, this thesis showcases a variety of functional bioprinted tissue models that enable the study of biological processes in vitro. The thorough exploration of volumetric bioprinting, distinguished by its scalability, unparalleled design freedom, compatibility with advanced biological tools, and a growing library of smart materials, charts new paths toward the creation of clinically-relevant testing platforms. The bioprinted, tissue-specific in vitro models presented here offer enhanced physiological accuracy and predictability and hold the potential to incorporate patient-specific elements for personalized medicine. The toolkit developed in here represents a significant stride in bridging the translational gap of tissue-engineered in vitro models, particularly in the context of preclinical testing. All in all, the evolving landscape of biofabricated in vitro models holds promise for innovative approaches in the future.

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

Singh

Moses

Bhardwaj

et al. 2021

Adv Healthcare Materials

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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.

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A human joint-on-a-chip as alternative to animal models in osteoarthritis

Cited by 4 publications

References 0 publications

A Novel Method Facilitating the Simple and Low-Cost Preparation of Human Osteochondral Slice Explants for Large-Scale Native Tissue Analysis

A Novel Method Facilitating the Simple and Low-Cost Preparation of Human Osteochondral Slice Explants for Large-Scale Native Tissue Analysis

Crafting Tissue Complexity

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

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