McDonough, C. M. & Jette, A. M. The contribution of osteoarthritis to functional limitations and disability. Clin. Geriatr. Med. 26, 387–399 (2010).
Google Scholar
Guo, Q. et al. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 6, 15 (2018).
Google Scholar
Chen, D. et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res. 5, 16044 (2017).
Google Scholar
Onishi, K. et al. Osteoarthritis: a critical review. Crit. Rev. Phys. Rehabil. Med. 24, 251–264 (2012).
Google Scholar
Aletaha, D. & Smolen, J. S. Diagnosis and management of rheumatoid arthritis: a review. JAMA 320, 1360–1372 (2018).
Google Scholar
Ghouri, A. & Conaghan, P. G. Update on novel pharmacological therapies for osteoarthritis. Ther. Adv. Musculoskelet. Dis. 11, 1759720–19864492 (2019).
Low, L. A., Mummery, C., Berridge, B. R., Austin, C. P. & Tagle, D. A. Organs-on-chips: into the next decade. Nat. Rev. Drug Discov. 20, 345–361 (2021).
Google Scholar
Jensen, C. & Teng, Y. Is it time to start transitioning from 2D to 3D cell culture? Front. Mol. Biosci. 7, 33 (2020).
Google Scholar
Kapalczynska, M. et al. 2D and 3D cell cultures — a comparison of different types of cancer cell cultures. Arch. Med. Sci. 14, 910–919 (2018).
Google Scholar
Duval, K. et al. Modeling physiological events in 2D vs. 3D cell culture. Physiology 32, 266–277 (2017).
Google Scholar
Huh, D., Hamilton, G. A. & Ingber, D. E. From 3D cell culture to organs-on-chips. Trends Cell Biol. 21, 745–754 (2011).
Google Scholar
Charlier, E. et al. Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem. Pharmacol. 165, 49–65 (2019).
Google Scholar
Bessis, N., Decker, P., Assier, E., Semerano, L. & Boissier, M. C. Arthritis models: usefulness and interpretation. Semin. Immunopathol. 39, 469–486 (2017).
Google Scholar
Malfait, A. M. & Little, C. B. On the predictive utility of animal models of osteoarthritis. Arthritis Res. Ther. 17, 225 (2015).
Google Scholar
Kuyinu, E. L., Narayanan, G., Nair, L. S. & Laurencin, C. T. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J. Orthop. Surg. Res. 11, 19 (2016).
Google Scholar
Dolzani, P. et al. Ex vivo physiological compression of human osteoarthritis cartilage modulates cellular and matrix components. PLoS ONE 14, e0222947 (2019).
Google Scholar
Kleuskens, M. W. A., van Donkelaar, C. C., Kock, L. M., Janssen, R. P. A. & Ito, K. An ex vivo human osteochondral culture model. J. Orthop. Res. 39, 871–879 (2021).
Google Scholar
Cope, P. J., Ourradi, K., Li, Y. & Sharif, M. Models of osteoarthritis: the good, the bad and the promising. Osteoarthritis Cartilage 27, 230–239 (2019).
Google Scholar
Sophia Fox, A. J., Bedi, A. & Rodeo, S. A. The basic science of articular cartilage: structure, composition, and function. Sports Health 1, 461–468 (2009).
Google Scholar
Burr, D. B. Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis. Osteoarthritis Cartilage 12, S20–30 (2004).
Google Scholar
Oegema, T. R. Jr, Carpenter, R. J., Hofmeister, F. & Thompson, R. C. Jr. The interaction of the zone of calcified cartilage and subchondral bone in osteoarthritis. Microsc. Res. Tech. 37, 324–332 (1997).
Google Scholar
Bonewald, L. F. The amazing osteocyte. J. Bone Min. Res. 26, 229–238 (2011).
Google Scholar
Feng, X. & Teitelbaum, S. L. Osteoclasts: new insights. Bone Res. 1, 11–26 (2013).
Google Scholar
Firestein, G. S. Evolving concepts of rheumatoid arthritis. Nature 423, 356–361 (2003).
Google Scholar
Simkin, P. A. Physiology of normal and abnormal synovium. Semin. Arthritis Rheum. 21, 179–183 (1991).
Google Scholar
Kurowska-Stolarska, M. & Alivernini, S. Synovial tissue macrophages: friend or foe? RMD Open 3, e000527 (2017).
Google Scholar
Brindle, T., Nyland, J. & Johnson, D. L. The meniscus: review of basic principles with application to surgery and rehabilitation. J. Athl. Train. 36, 160–169 (2001).
Google Scholar
Lieben, L. Characterization of the infrapatellar fat pad. Nat. Rev. Rheumatol. 13, 571–571 (2017).
Google Scholar
Labusca, L. & Zugun-Eloae, F. The unexplored role of intra-articular adipose tissue in the homeostasis and pathology of articular joints. Front. Vet. Sci. 5, 35 (2018).
Google Scholar
Bhatia, S. N. & Ingber, D. E. Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760–772 (2014).
Google Scholar
Zheng, F. et al. Organ-on-a-chip systems: microengineering to biomimic living systems. Small 12, 2253–2282 (2016).
Google Scholar
Bhise, N. S. et al. Organ-on-a-chip platforms for studying drug delivery systems. J. Control. Rel. 190, 82–93 (2014).
Google Scholar
Kimura, H., Sakai, Y. & Fujii, T. Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab. Pharmacokinet. 33, 43–48 (2018).
Google Scholar
Wilmer, M. J. et al. Kidney-on-a-chip technology for drug-induced nephrotoxicity screening. Trends Biotechnol. 34, 156–170 (2016).
Google Scholar
Kaarj, K. & Yoon, J. Y. Methods of delivering mechanical stimuli to organ-on-a-chip. Micromachines 10, 700 (2019).
Google Scholar
Thompson, C. L., Fu, S., Knight, M. M. & Thorpe, S. D. Mechanical stimulation: a crucial element of organ-on-chip models. Front. Bioeng. Biotechnol. 8, 602646 (2020).
Google Scholar
Wu, Q. et al. Organ-on-a-chip: recent breakthroughs and future prospects. Biomed. Eng. Online 19, 9 (2020).
Google Scholar
Doryab, A., Amoabediny, G. & Salehi-Najafabadi, A. Advances in pulmonary therapy and drug development: lung tissue engineering to lung-on-a-chip. Biotechnol. Adv. 34, 588–596 (2016).
Google Scholar
Shrestha, J. et al. Lung-on-a-chip: the future of respiratory disease models and pharmacological studies. Crit. Rev. Biotechnol. 40, 213–230 (2020).
Google Scholar
Moradi, E., Jalili-Firoozinezhad, S. & Solati-Hashjin, M. Microfluidic organ-on-a-chip models of human liver tissue. Acta Biomater. 116, 67–83 (2020).
Google Scholar
Kim, J. et al. Three-dimensional human liver-chip emulating premetastatic niche formation by breast cancer-derived extracellular vesicles. ACS Nano 14, 14971–14988 (2020).
Google Scholar
Jellali, R. et al. Long-term human primary hepatocyte cultures in a microfluidic liver biochip show maintenance of mRNA levels and higher drug metabolism compared with Petri cultures. Biopharm. Drug Dispos. 37, 264–275 (2016).
Google Scholar
Lee, J. & Kim, S. Kidney-on-a-chip: a new technology for predicting drug efficacy, interactions, and drug-induced nephrotoxicity. Curr. Drug Metab. 19, 577–583 (2018).
Google Scholar
Ashammakhi, N., Wesseling-Perry, K., Hasan, A., Elkhammas, E. & Zhang, Y. S. Kidney-on-a-chip: untapped opportunities. Kidney Int. 94, 1073–1086 (2018).
Google Scholar
Bein, A. et al. Microfluidic organ-on-a-chip models of human intestine. Cell Mol. Gastroenterol. Hepatol. 5, 659–668 (2018).
Google Scholar
Verhulsel, M. et al. Developing an advanced gut on chip model enabling the study of epithelial cell/fibroblast interactions. Lab. Chip 21, 365–377 (2021).
Google Scholar
Zhang, Y. S. et al. From cardiac tissue engineering to heart-on-a-chip: beating challenges. Biomed. Mater. 10, 034006 (2015).
Google Scholar
Ribas, J. et al. Cardiovascular organ-on-a-chip platforms for drug discovery and development. Appl. Vitr. Toxicol. 2, 82–96 (2016).
Ferraz, M. A. M. M. et al. An oviduct-on-a-chip provides an enhanced in vitro environment for zygote genome reprogramming. Nat. Commun. 9, 4934 (2018).
Google Scholar
Kim, S., Kim, W., Lim, S. & Jeon, J. S. Vasculature-on-a-chip for in vitro disease models. Bioengineering 4, 8 (2017).
Google Scholar
Moses, S. R., Adorno, J. J., Palmer, A. F. & Song, J. W. Vessel-on-a-chip models for studying microvascular physiology, transport, and function in vitro. Am. J. Physiol. Cell Physiol. 320, C92–C105 (2021).
Google Scholar
Doherty, E. L., Aw, W. Y., Hickey, A. J. & Polacheck, W. J. Microfluidic and organ-on-a-chip approaches to investigate cellular and microenvironmental contributions to cardiovascular function and pathology. Front. Bioeng. Biotechnol. 9, 624435 (2021).
Google Scholar
Oddo, A. et al. Advances in microfluidic blood-brain barrier (BBB) models. Trends Biotechnol. 37, 1295–1314 (2019).
Google Scholar
Virumbrales-Munoz, M. et al. Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models. Sci. Rep. 7, 11998 (2017).
Google Scholar
Liu, X. et al. Tumor-on-a-chip: from bioinspired design to biomedical application. Microsyst. Nanoeng. 7, 50 (2021).
Google Scholar
Sontheimer-Phelps, A., Hassell, B. A. & Ingber, D. E. Modelling cancer in microfluidic human organs-on-chips. Nat. Rev. Cancer 19, 65–81 (2019).
Google Scholar
Picollet-D’hahan, N., Zuchowska, A., Lemeunier, I. & Le Gac, S. Multiorgan-on-a-chip: a systemic approach to model and decipher inter-organ communication. Trends Biotechnol. 39, 788–810 (2021).
Google Scholar
Sung, J. H. et al. Recent advances in body-on-a-chip systems. Anal. Chem. 91, 330–351 (2019).
Google Scholar
Piluso, S. et al. Mimicking the articular joint with in vitro models. Trends Biotechnol. 37, 1063–1077 (2019).
Google Scholar
Longobardi, L. et al. Synovial joints: from development to homeostasis. Curr. Osteoporos. Rep. 13, 41–51 (2015).
Google Scholar
Ikada, Y. Challenges in tissue engineering. J. R. Soc. Interface 3, 589–601 (2006).
Google Scholar
Fu, Y. et al. Engineering cartilage tissue by co-culturing of chondrocytes and mesenchymal stromal cells. Methods Mol. Biol. 2221, 53–70 (2021).
Google Scholar
Gartland, A., Rumney, R. M., Dillon, J. P. & Gallagher, J. A. Isolation and culture of human osteoblasts. Methods Mol. Biol. 806, 337–355 (2012).
Google Scholar
Park, D., Lim, J., Park, J. Y. & Lee, S. H. Concise review: stem cell microenvironment on a chip: current technologies for tissue engineering and stem cell biology. Stem Cell Transl. Med. 4, 1352–1368 (2015).
Google Scholar
Pittenger, M. F. et al. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen. Med. 4, 22 (2019).
Google Scholar
Augello, A. & De Bari, C. The regulation of differentiation in mesenchymal stem cells. Hum. Gene Ther. 21, 1226–1238 (2010).
Google Scholar
George, J., Kuboki, Y. & Miyata, T. Differentiation of mesenchymal stem cells into osteoblasts on honeycomb collagen scaffolds. Biotechnol. Bioeng. 95, 404–411 (2006).
Google Scholar
Chen, Q. et al. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differ. 23, 1128–1139 (2016).
Google Scholar
Somoza, R. A., Welter, J. F., Correa, D. & Caplan, A. I. Chondrogenic differentiation of mesenchymal stem cells: challenges and unfulfilled expectations. Tissue Eng. Part B Rev. 20, 596–608 (2014).
Google Scholar
Karagiannis, P. et al. Induced pluripotent stem cells and their use in human models of disease and development. Physiol. Rev. 99, 79–114 (2019).
Google Scholar
Guzzo, R. M. & Drissi, H. Differentiation of human induced pluripotent stem cells to chondrocytes. Methods Mol. Biol. 1340, 79–95 (2015).
Google Scholar
Jeon, O. H. et al. Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials. Sci. Rep. 6, 26761 (2016).
Google Scholar
Williams, I. M. & Wu, J. C. Generation of endothelial cells from human pluripotent stem cells. Arterioscler. Thromb. Vasc. Biol. 39, 1317–1329 (2019).
Google Scholar
Gunhanlar, N. et al. A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells. Mol. Psychiatry 23, 1336–1344 (2018).
Google Scholar
Nakajima, T. et al. Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture. Nat. Commun. 12, 5012 (2021).
Google Scholar
Mukherjee, C., Hale, C. & Mukhopadhyay, S. A simple multistep protocol for differentiating human induced pluripotent stem cells into functional macrophages. Methods Mol. Biol. 1784, 13–28 (2018).
Google Scholar
Doss, M. X. & Sachinidis, A. Current challenges of iPSC-based disease modeling and therapeutic implications. Cells 8, 403 (2019).
Google Scholar
Ben Jehuda, R., Shemer, Y. & Binah, O. Genome editing in induced pluripotent stem cells using CRISPR/Cas9. Stem Cell Rev. Rep. 14, 323–336 (2018).
Google Scholar
Adkar, S. S. et al. Step-wise chondrogenesis of human induced pluripotent stem cells and purification via a reporter allele generated by CRISPR-Cas9 genome editing. Stem Cell 37, 65–76 (2019)
Google Scholar
Roeder, E., Matthews, B. G. & Kalajzic, I. Visual reporters for study of the osteoblast lineage. Bone 92, 189–195 (2016).
Google Scholar
Bader, D. L., Salter, D. M. & Chowdhury, T. T. Biomechanical influence of cartilage homeostasis in health and disease. Arthritis 2011, 979032 (2011).
Google Scholar
Almqvist, K. F. et al. Treatment of cartilage defects in the knee using alginate beads containing human mature allogenic chondrocytes. Am. J. Sport. Med. 37, 1920–1929 (2009).
Salati, M. A. et al. Agarose-based biomaterials: opportunities and challenges in cartilage tissue engineering. Polymers 12, 1150. (2020).
Google Scholar
Jin, R. et al. Enzymatically crosslinked dextran-tyramine hydrogels as injectable scaffolds for cartilage tissue engineering. Tissue Eng. Part A 16, 2429–2440 (2010).
Google Scholar
Deshpande, M. C. et al. The effect of poly(ethylene glycol) molecular architecture on cellular interaction and uptake of DNA complexes. J. Control. Rel. 97, 143–156 (2004).
Google Scholar
Bougault, C., Paumier, A., Aubert-Foucher, E. & Mallein-Gerin, F. Molecular analysis of chondrocytes cultured in agarose in response to dynamic compression. BMC Biotechnol. 8, 71 (2008).
Google Scholar
Benya, P. D. & Shaffer, J. D. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30, 215–224 (1982).
Google Scholar
Buschmann, M. D., Gluzband, Y. A., Grodzinsky, A. J., Kimura, J. H. & Hunziker, E. B. Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix. J. Orthop. Res. 10, 745–758 (1992).
Google Scholar
Bougault, C. et al. Dynamic compression of chondrocyte-agarose constructs reveals new candidate mechanosensitive genes. PLoS ONE 7, e36964 (2012).
Google Scholar
Ashraf, S. & Walsh, D. A. Angiogenesis in osteoarthritis. Curr. Opin. Rheumatol. 20, 573–580 (2008).
Google Scholar
Ahearne, M. Introduction to cell-hydrogel mechanosensing. Interface Focus. 4, 20130038 (2014).
Google Scholar
Wennink, J. W. H. et al. Injectable hydrogels by enzymatic co-crosslinking of dextran and hyaluronic acid tyramine conjugates. Macromol. Symp. 309–310, 213–221 (2011).
Jin, R. et al. Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran-hyaluronic acid conjugates for cartilage tissue engineering. Biomaterials 31, 3103–3113 (2010).
Google Scholar
Occhetta, P. et al. Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip model. Nat. Biomed. Eng. 3, 545–557 (2019).
Google Scholar
Lee, D., Erickson, A., You, T., Dudley, A. T. & Ryu, S. Pneumatic microfluidic cell compression device for high-throughput study of chondrocyte mechanobiology. Lab. Chip 18, 2077–2086 (2018).
Google Scholar
Rosser, J. et al. Microfluidic nutrient gradient-based three-dimensional chondrocyte culture-on-a-chip as an in vitro equine arthritis model. Mater. Today Bio 4, 100023 (2019).
Google Scholar
Paggi, C. A., Venzac, B., Karperien, M., Leijten, J. C. H. & Le Gac, S. Monolithic microfluidic platform for exerting gradients of compression on cell-laden hydrogels, and application to a model of the articular cartilage. Sens. Actuat. B Chem. 315, 127917 (2020).
Google Scholar
Jusoh, N., Oh, S., Kim, S., Kim, J. & Jeon, N. L. Microfluidic vascularized bone tissue model with hydroxyapatite-incorporated extracellular matrix. Lab. Chip 15, 3984–3988 (2015).
Google Scholar
Yuan, H. et al. Osteoinductive ceramics as a synthetic alternative to autologous bone grafting. Proc. Natl Acad. Sci. USA 107, 13614–13619 (2010).
Google Scholar
Goncalves, A. M., Moreira, A., Weber, A., Williams, G. R. & Costa, P. F. Osteochondral tissue engineering: the potential of electrospinning and additive manufacturing. Pharmaceutics 13, 983 (2021).
Google Scholar
Mansoorifar, A., Gordon, R., Bergan, R. C. & Bertassoni, L. E. Bone-on-a-chip: microfluidic technologies and microphysiologic models of bone tissue. Adv. Funct. Mater. 14, e1702787 (2021).
Torisawa, Y. S. et al. Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat. Methods 11, 663–669 (2014).
Google Scholar
Bersini, S. et al. A microfluidic 3D in vitro model for specificity of breast cancer metastasis to bone. Biomaterials 35, 2454–2461 (2014).
Google Scholar
Chou, D. B. et al. On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat. Biomed. Eng. 4, 394–406 (2020).
Google Scholar
Yamada, A. et al. Transient microfluidic compartmentalization using actionable microfilaments for biochemical assays, cell culture and organs-on-chip. Lab. Chip 16, 4691–4701 (2016).
Google Scholar
Hoemann, C. D., Lafantaisie-Favreau, C. H., Lascau-Coman, V., Chen, G. & Guzman-Morales, J. The cartilage-bone interface. J. Knee Surg. 25, 85–97 (2012).
Google Scholar
Simkin, P. A. Consider the tidemark. J. Rheumatol. 39, 890–892 (2012).
Google Scholar
Lin, H., Lozito, T. P., Alexander, P. G., Gottardi, R. & Tuan, R. S. Stem cell-based microphysiological osteochondral system to model tissue response to interleukin-1beta. Mol. Pharm. 11, 2203–2212 (2014).
Google Scholar
Pirosa, A. et al. An in vitro chondro-osteo-vascular triphasic model of the osteochondral complex. Biomaterials 272, 120773 (2021).
Google Scholar
Lin, Z. et al. Osteochondral tissue chip derived from iPSCs: modeling OA pathologies and testing drugs. Front. Bioeng. Biotechnol. 7, 411 (2019).
Google Scholar
Moraes, C., Mehta, G., Lesher-Perez, S. C. & Takayama, S. Organs-on-a-chip: a focus on compartmentalized microdevices. Ann. Biomed. Eng. 40, 1211–1227 (2012).
Google Scholar
Rothbauer, M. et al. Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing. Lab. Chip 20, 1461–1471 (2020).
Google Scholar
Ma, H. P. et al. A microfluidic chip-based co-culture of fibroblast-like synoviocytes with osteoblasts and osteoclasts to test bone erosion and drug evaluation. R. Soc. Open Sci. 5, 180528 (2018).
Google Scholar
Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010).
Google Scholar
Kim, H. J., Huh, D., Hamilton, G. & Ingber, D. E. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab. Chip 12, 2165–2174 (2012).
Google Scholar
Sinha, R. et al. Endothelial cell alignment as a result of anisotropic strain and flow induced shear stress combinations. Sci. Rep. 6, 29510 (2016).
Google Scholar
Petersen, W. & Tillmann, B. Structure and vascularization of the cruciate ligaments of the human knee joint. Anat. Embryol. 200, 325–334 (1999).
Google Scholar
Lee, P., Lin, R., Moon, J. & Lee, L. P. Microfluidic alignment of collagen fibers for in vitro cell culture. Biomed. Microdevices 8, 35–41 (2006).
Google Scholar
Phan, D. T. T. et al. A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. Lab. Chip 17, 511–520 (2017).
Google Scholar
Hsu, Y. H., Moya, M. L., Hughes, C. C. W., George, S. C. & Lee, A. P. A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays. Lab. Chip 13, 2990–2998 (2013).
Google Scholar
Yang, F. et al. A 3D human adipose tissue model within a microfluidic device. Lab. Chip 21, 435–446 (2021).
Google Scholar
Clockaerts, S. et al. The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review. Osteoarthritis Cartilage 18, 876–882 (2010).
Google Scholar
Fontanella, C. G. et al. Biomechanical behavior of Hoffa’s fat pad in healthy and osteoarthritic conditions: histological and mechanical investigations. Australas. Phys. Eng. Sci. Med. 41, 657–667 (2018).
Google Scholar
Kongsuphol, P. et al. In vitro micro-physiological model of the inflamed human adipose tissue for immune-metabolic analysis in type II diabetes. Sci. Rep. 9, 4887 (2019).
Google Scholar
Liu, Y. et al. Adipose-on-a-chip: a dynamic microphysiological in vitro model of the human adipose for immune-metabolic analysis in type II diabetes. Lab. Chip 19, 241–253 (2019).
Google Scholar
Loskill, P., Marcus, S. G., Mathur, A., Reese, W. M. & Healy, K. μOrgano: a Lego®-like plug & play system for modular multi-organ-chips. PLoS ONE 10, e0139587 (2015).
Google Scholar
Zhang, Y. S. et al. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc. Natl Acad. Sci. USA 114, E2293–E2302 (2017).
Google Scholar
Ong, L. J. Y. et al. Self-aligning Tetris-Like (TILE) modular microfluidic platform for mimicking multi-organ interactions. Lab. Chip 19, 2178–2191 (2019).
Google Scholar
Esch, M. B., Ueno, H., Applegate, D. R. & Shuler, M. L. Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue. Lab. Chip 16, 2719–2729 (2016).
Google Scholar
Materne, E. M. et al. A multi-organ chip co-culture of neurospheres and liver equivalents for long-term substance testing. J. Biotechnol. 205, 36–46 (2015).
Google Scholar
Maschmeyer, I. et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab. Chip 15, 2688–2699 (2015).
Google Scholar
Bortel, E. L., Charbonnier, B. & Heuberger, R. Development of a synthetic synovial fluid for tribological testing. Lubricants 3, 664–686 (2015).
Park, D., Lee, J., Chung, J. J., Jung, Y. & Kim, S. H. Integrating organs-on-chips: multiplexing, scaling, vascularization, and innervation. Trends Biotechnol. 38, 99–112 (2020).
Google Scholar
Moraes, C. et al. On being the right size: scaling effects in designing a human-on-a-chip. Integr. Biol. 5, 1149–1161 (2013).
Google Scholar
Harink, B., Le Gac, S., Barata, D., van Blitterswijk, C. & Habibovic, P. Microtiter plate-sized standalone chip holder for microenvironmental physiological control in gas-impermeable microfluidic devices. Lab. Chip 14, 1816–1820 (2014).
Google Scholar
Palacio-Castaneda, V., Kooijman, L., Venzac, B., Verdurmen, W. P. R. & Le Gac, S. Metabolic switching of tumor cells under hypoxic conditions in a tumor-on-a-chip model. Micromachines 11, 382 (2020).
Google Scholar
Sleeboom, J. J. F., Den Toonder, J. M. J. & Sahlgren, C. M. MDA-MB-231 breast cancer cells and their CSC population migrate towards low oxygen in a microfluidic gradient device. Int. J. Mol. Sci. 19, 3047 (2018).
Google Scholar
Wilkins, R. J., Browning, J. A. & Ellory, J. C. Surviving in a matrix: membrane transport in articular chondrocytes. J. Membr. Biol. 177, 95–108 (2000).
Google Scholar
Hall, A. C., Horwitz, E. R. & Wilkins, R. J. The cellular physiology of articular cartilage. Exp. Physiol. 81, 535–545 (1996).
Google Scholar
Arnett, T. R. Extracellular pH regulates bone cell function. J. Nutr. 138, 415S–418S (2008).
Google Scholar
Goldie, I. & Nachemson, A. Synovial pH in rheumatoid knee-joints. I. The effect of synovectomy. Acta Orthop. Scand. 40, 634–641 (1969).
Google Scholar
Konttinen, Y. T. et al. Acidic cysteine endoproteinase cathepsin K in the degeneration of the superficial articular hyaline cartilage in osteoarthritis. Arthritis Rheum. 46, 953–960 (2002).
Google Scholar
Scherer, H. U. & Burmester, G. R. Adaptive immunity in rheumatic diseases: bystander or pathogenic player? Best Pract. Res. Clin. Rheumatol. 25, 785–800 (2011).
Google Scholar
Mobasheri, A. et al. Recent advances in understanding the phenotypes of osteoarthritis. F1000Res. 8, 2091 (2019).
Google Scholar
Morsink, M. A. J., Willemen, N. G. A., Leijten, J., Bansal, R. & Shin, S. R. Immune organs and immune cells on a chip: an overview of biomedical applications. Micromachines 11, 849 (2020).
Google Scholar
Torisawa, Y. S. et al. Modeling hematopoiesis and responses to radiation countermeasures in a bone marrow-on-a-chip. Tissue Eng. Part C. Methods 22, 509–515 (2016).
Google Scholar
Bruce, A. et al. Three-dimensional microfluidic tri-culture model of the bone marrow microenvironment for study of acute lymphoblastic leukemia. PLoS ONE 10, e0140506 (2015).
Google Scholar
Ramadan, Q. & Ting, F. C. In vitro micro-physiological immune-competent model of the human skin. Lab. Chip 16, 1899–1908 (2016).
Google Scholar
Ramadan, Q. et al. NutriChip: nutrition analysis meets microfluidics. Lab. Chip 13, 196–203 (2013).
Google Scholar
Mondadori, C. et al. Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint. Biofabrication 13, 045001 (2021).
Google Scholar
Hamza, B. & Irimia, D. Whole blood human neutrophil trafficking in a microfluidic model of infection and inflammation. Lab. Chip 15, 2625–2633 (2015).
Google Scholar
Han, S. et al. A versatile assay for monitoring in vivo-like transendothelial migration of neutrophils. Lab. Chip 12, 3861–3865 (2012).
Google Scholar
Grässel, S. The role of peripheral nerve fibers and their neurotransmitters in cartilage and bone physiology and pathophysiology. Arthritis Res. Ther. 16, 485 (2014).
Google Scholar
Eitner, A., Pester, J., Nietzsche, S., Hofmann, G. O. & Schaible, H. G. The innervation of synovium of human osteoarthritic joints in comparison with normal rat and sheep synovium. Osteoarthritis Cartilage 21, 1383–1391 (2013).
Google Scholar
Gribi, S., du Bois de Dunilac, S., Ghezzi, D. & Lacour, S. P. A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers. Nat. Commun. 9, 4403 (2018).
Google Scholar
Sharma, A. D. et al. Engineering a 3D functional human peripheral nerve in vitro using the Nerve-on-a-Chip platform. Sci. Rep. 9, 8921 (2019).
Google Scholar
Park, S. E. et al. A three-dimensional in vitro model of the peripheral nervous system. NPG Asia Mater. 13, 2 (2021).
Kundu, A. et al. Fabrication and characterization of 3D Printed, 3D microelectrode arrays for interfacing with a peripheral nerve-on-a-chip. ACS Biomater. Sci. Eng. 7, 3018–3029 (2021).
Google Scholar
Marzioch, J. et al. On-chip photodynamic therapy — monitoring cell metabolism using electrochemical microsensors. Lab. Chip 18, 3353–3360 (2018).
Google Scholar
Rivera, K. R., Yokus, M. A., Erb, P. D., Pozdin, V. A. & Daniele, M. Measuring and regulating oxygen levels in microphysiological systems: design, material, and sensor considerations. Analyst 144, 3190–3215 (2019).
Google Scholar
Bonk, S. M. et al. Design and characterization of a sensorized microfluidic cell-culture system with electro-thermal micro-pumps and sensors for cell adhesion, oxygen, and pH on a glass chip. Biosensors 5, 513–536 (2015).
Google Scholar
Kieninger, J., Weltin, A., Flamm, H. & Urban, G. A. Microsensor systems for cell metabolism — from 2D culture to organ-on-chip. Lab. Chip 18, 1274–1291 (2018).
Google Scholar
Grist, S. M., Chrostowski, L. & Cheung, K. C. Optical oxygen sensors for applications in microfluidic cell culture. Sensors 10, 9286–9316 (2010).
Google Scholar
Zhu, J. et al. An integrated adipose-tissue-on-chip nanoplasmonic biosensing platform for investigating obesity-associated inflammation. Lab. Chip 18, 3550–3560 (2018).
Google Scholar
Ragab, G., Elshahaly, M. & Bardin, T. Gout: an old disease in new perspective — a review. J. Adv. Res. 8, 495–511 (2017).
Google Scholar
Quiros-Solano, W. F. et al. Microfabricated tuneable and transferable porous PDMS membranes for organs-on-chips. Sci. Rep. 8, 13524 (2018).
Google Scholar
Becker, H. Mind the gap! Lab. Chip 10, 271–273 (2010).
Google Scholar
Berthier, E., Young, E. W. & Beebe, D. Engineers are from PDMS-land, biologists are from polystyrenia. Lab. Chip 12, 1224–1237 (2012).
Google Scholar
van Meer, B. J. et al. Small molecule absorption by PDMS in the context of drug response bioassays. Biochem. Biophys. Res. Commun. 482, 323–328 (2017).
Google Scholar
Ramadan, Q. & Zourob, M. Organ-on-a-chip engineering: toward bridging the gap between lab and industry. Biomicrofluidics 14, 041501 (2020).
Google Scholar
Allwardt, V. et al. Translational roadmap for the organs-on-a-chip industry toward broad adoption. Bioengineering 7, 112 (2020).
Google Scholar
Ma, C., Peng, Y., Li, H. & Chen, W. Organ-on-a-chip: a new paradigm for drug development. Trends Pharmacol. Sci. 42, 119–133 (2021).
Google Scholar
Zhou, T. et al. Generation of induced pluripotent stem cells from urine. J. Am. Soc. Nephrol. 22, 1221–1228 (2011).
Google Scholar
Lozito, T. P. et al. Three-dimensional osteochondral microtissue to model pathogenesis of osteoarthritis. Stem Cell Res. Ther. 4, S6 (2013).
Google Scholar
