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      Drug Design, Development and Therapy (submit here)

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      Advances in Engineered Three-Dimensional (3D) Body Articulation Unit Models


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          Indeed, the body articulation units, commonly referred to as body joints, play significant roles in the musculoskeletal system, enabling body flexibility. Nevertheless, these articulation units suffer from several pathological conditions, such as osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, gout, and psoriatic arthritis. There exist several treatment modalities based on the utilization of anti-inflammatory and analgesic drugs, which can reduce or control the pathophysiological symptoms. Despite the success, these treatment modalities suffer from major shortcomings of enormous cost and poor recovery, limiting their applicability and requiring promising strategies. To address these limitations, several engineering strategies have been emerged as promising solutions in fabricating the body articulation as unit models towards local articulation repair for tissue regeneration and high-throughput screening for drug development. In this article, we present challenges related to the selection of biomaterials (natural and synthetic sources), construction of 3D articulation models (scaffold-free, scaffold-based, and organ-on-a-chip), architectural designs (microfluidics, bioprinting, electrospinning, and biomineralization), and the type of culture conditions (growth factors and active peptides). Then, we emphasize the applicability of these articulation units for emerging biomedical applications of drug screening and tissue repair/regeneration. In conclusion, we put forward the challenges and difficulties for the further clinical application of the in vitro 3D articulation unit models in terms of the long-term high activity of the models.

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          Most cited references162

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          The bone marrow niche for haematopoietic stem cells.

          Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their niches, but the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Recent progress has been made in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum and functional heterogeneity among perivascular microenvironments.
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            Modeling Physiological Events in 2D vs. 3D Cell Culture

            Cell culture has become an indispensable tool to help uncover fundamental biophysical and biomolecular mechanisms by which cells assemble into tissues and organs, how these tissues function, and how that function becomes disrupted in disease. Cell culture is now widely used in biomedical research, tissue engineering, regenerative medicine, and industrial practices. Although flat, two-dimensional (2D) cell culture has predominated, recent research has shifted toward culture using three-dimensional (3D) structures, and more realistic biochemical and biomechanical microenvironments. Nevertheless, in 3D cell culture, many challenges remain, including the tissue-tissue interface, the mechanical microenvironment, and the spatiotemporal distributions of oxygen, nutrients, and metabolic wastes. Here, we review 2D and 3D cell culture methods, discuss advantages and limitations of these techniques in modeling physiologically and pathologically relevant processes, and suggest directions for future research.
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              Extracellular matrix degradation and remodeling in development and disease.

              The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                18 January 2022
                : 16
                : 213-235
                [1 ]Institute of Biomaterials and Tissue Engineering, Huaqiao University , Xiamen, 361021, Fujian, People’s Republic of China
                [2 ]Fujian Provincial Key Laboratory of Biochemical Technology (Huaqiao University) , Xiamen, 361021, Fujian, People’s Republic of China
                [3 ]Affiliated Dongguan Hospital, Southern Medical University , Dongguan, 523059, Guangdong, People’s Republic of China
                [4 ]Guangdong Provincial Key Laboratory of Shock and Microcirculation , Guangzhou, 510080, Guangdong, People’s Republic of China
                Author notes
                Correspondence: Ranjith Kumar Kankala; Ai-Zheng Chen Institute of Biomaterials and Tissue Engineering, Huaqiao University , Xiamen, 361021, People’s Republic of China Email azchen@hqu.edu.cn; ranjithkankala@hqu.edu.cn
                Author information
                © 2022 Chen et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 12 October 2021
                : 24 December 2021
                Page count
                Figures: 0, Tables: 2, References: 163, Pages: 23

                Pharmacology & Pharmaceutical medicine
                3d models,articulation disease,drug screening,bioprinting,tissue regeneration


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