Biomaterials Translational ›› 2024, Vol. 5 ›› Issue (4): 411-424.doi: 10.12336/biomatertransl.2024.04.006
• REVIEW • Previous Articles Next Articles
Jun Li1, Honghao Hou2, Qian Li1, Junjie Liu2, Yunlong Zhao3,4, Chaoran Zhao2, Zhentao Li(), Leyu Wang1,*(
), Xiaozhong Qiu2,*(
)
Received:
2024-09-29
Revised:
2024-10-17
Accepted:
2024-10-22
Online:
2024-11-14
Published:
2024-12-28
Contact:
Xiaozhong Qiu, qqiuxzh@163.com;Leyu Wang, wangleyu889@163.com;Zhentao Li, drlzt312@163.com.
Li, J.; Hou, H.; Li, Q.; Liu, J.;Zhao, Y.; Zhao, C.; Li, Z.; Wang, L.; Qiu, X. Cardiac organ chip: advances in construction and application. Biomater Transl. 2024, 5(4), 411-424.
Figure 2. Microfluidic platform. (A) Custom–designed electronic circuitry. (B) Schematic of the bioreactor platform with an array of bioreactors for large–scale production of cardiac tissues along with the cross–sectional view. (C) Schematic and images of the cardiac tissue formation. Reprinted from Parsa et al.18 Copyright 2017 The Royal Society of Chemistry.
Figure 3. Fabrication of heart–on–chips and cardiac tissue scaffolds. (A) Assembly of a conical cardiac ventricle through (I, II) soft lithography of PDMS master molds, (III–V) replica molding of PICO, (VI, VII) and CMs cultured on the scaffold and (VIII–X) scaffold wrapping using a mandrel which is later removed. Reprinted from Mohammadi et al.30 Copyright 2022 Wiley‐VCH GmbH. (B) Application of a reinforced PDMS mould for hot embossing of COP to produce microfluidic chips. Reprinted from Qin et al.25 Copyright 2022 Royal Society of Chemistry. (C) 3D printing of bioelastomer prepolymers using a co–axial needle to create vascular tubes. The carbomer was used as a supporting bath. Reprinted from Savoji et al.29 Copyright 2020 American Chemical Society. (D) Fabrication of AngioTubes through the casting of 1,2,4 prepolymer into PDMS moulds to create the top and bottom layers of the tubes, which are then aligned and 3D–stamped. Reprinted from Lai et al.24 3D: three–dimensional; CM: cardiomyocyte; PBS: phosphate buffered saline; PDMS: polydimethylsiloxane; PEG: polyethylene glycol; PICO: polycarbonate; UV: ultraviolet rays.
Figure 4. Cardiac organ chip hydrogel construction material. Created with Adobe Photoshop 2023. GelMA: methacrylated gelatine; PCL: polycaprolactone; PEGDA: poly(ethylene glycol) diacrylate.
Figure 5. (A) Diagram of the electrical stimulator assembled parts. Reprinted from Aragón et al.40 (B) The cardiac microphysiological system. Reprinted from Mathur et al.42 PDMS: polydimethylsiloxane.
Figure 6. (A) The use of organ–on–a–chip can disrupt drug development at multiple points: mechanistic studies of drug action, preclinical trials of drug toxicity and efficacy, clinical studies using patient–specific organ–on–a–chip for models of patient diversity, and the development of a ‘‘clinical–trial–on–a–chip’’ to discover therapeutic options for rare diseases. Reprinted from Ronaldson–Bouchard et al.50 (B) Schematic for drug screening enabled by the heart–on–a–chip platform. Reprinted from Ren et al.51 Copyright 2020 Wiley‐VCH GmbH. CAR: carbachol; CP: cyclophosphamide; CX43: connexin 43; DOX: doxorubicin; IVA: ivabradine; M: muscarinic; OOC: organic–on–a–chip; PDMS: polydimethylsiloxane; PMMA: polymethyl methacrylate; ROS: reactive oxygen species; TOP 2β: topoisomerase II–β.
Figure 7. (A) Disease modelling using the heart–on–a–chip. Reprinted from Mourad et al.57 Copyright 2023 American Heart Association, Inc. (B) Heart–on–a–chip devices can recapitulate cardiac functions in vitro and integrate sensing units to monitor the cells in culture. Reprinted from Paloschi et al.48 (C) Preparation of 3D cardiac microtissues. Scale bars: 100 μm. Reprinted from Abulaiti et al.58 3D: three–dimensional; CM: cardiomyocyte; cTnT: cardiac isoform of troponin–T; DAPI: 4′,6–diamidino–2–phenylindole; EC: endothelial cells; ECM: extracellular matrix; H–E: haematoxylin–eosin; HOC: heart–on–chip; hPSC–CM: human induced pluripotent stem cell‐derived cardiomyocytes; MC: mural cells; SR: sirius red.
Figure 8. (A) Overview of the bioreactor, immunofluorescence images demonstrating the presence of aligned and cross–striated iPS–CMs along the edge of the construct. Reprinted from Chen and Vunjak–Novakovic61 Copyright 2019, Mary Ann Liebert, Inc. (B) Dose–dependent hypertrophic response. Reprinted from Parsa et al.18 Copyright 2017 The Royal Society of Chemistry. 3D: three–dimensional; ANP: atrial natriuretic peptide; iPS–CMs: induced pluripotent stem cell–derived cardiomyocytes.
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