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Microengineering in cardiovascular research: new developments and translational applications.

Chan JM, Wong KH, Richards AM, Drum CL - Cardiovasc. Res. (2015)

Bottom Line: Microfluidic, cellular co-cultures that approximate macro-scale biology are important tools for refining the in vitro study of organ-level function and disease.Here we review applications of these technologies specific to the cardiovascular field, emphasizing three general categories of use: reductionist vascular models, tissue-engineered vascular models, and point-of-care diagnostics.With continued progress in the ability to purposefully control microscale environments, the detailed study of both primary and cultured cells may find new relevance in the general cardiovascular research community.

View Article: PubMed Central - PubMed

Affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

No MeSH data available.


Related in: MedlinePlus

Microfluidic devices to study thrombosis. (A) Schematic representation of a collagen hydrogel scaffold embedded with perivascular cells such as human brain vascular pericytes (HBVPs) and microchannels lined with ECs. (B) Whole blood was perfused at 10 µL/min through quiescent (control) and stimulated vessels at time points of 5, 50, 100, 150, and 250 s after initiation of stimulation. The platelets are labelled green with antibodies against platelet-specific glycoprotein IIb (integrin αIIb); an arrow indicates flow direction. Scale, 100 µm. Reproduced with permission from Zheng et al.35.
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CVV049F3: Microfluidic devices to study thrombosis. (A) Schematic representation of a collagen hydrogel scaffold embedded with perivascular cells such as human brain vascular pericytes (HBVPs) and microchannels lined with ECs. (B) Whole blood was perfused at 10 µL/min through quiescent (control) and stimulated vessels at time points of 5, 50, 100, 150, and 250 s after initiation of stimulation. The platelets are labelled green with antibodies against platelet-specific glycoprotein IIb (integrin αIIb); an arrow indicates flow direction. Scale, 100 µm. Reproduced with permission from Zheng et al.35.

Mentions: While single tubes can be easily produced by needle molding, interconnected networks of channels in hydrogels are best generated using lithographic techniques.32 It is worth pointing out the intrinsic merits of using ECM hydrogels here: because they are natural substrates for cell adhesion and can be remodelled by cells (as opposed to PDMS), the endothelium is capable of remodelling the channels and rounding up the sharp corners, producing channels that are still rectangular, but with curved corners.33 These properties enabled the generation of patterned, confluent microvascular networks that are entirely encased by ECM scaffolds.33,34 Zheng et al.35 designed such a perfused microvascular network in collagen scaffolds (Figure 3A) to study angiogenesis, pericyte-endothelial cell interactions, and thrombotic events during an inflammatory response. Vascular networks composed of HUVECs were allowed to mature for 7 days in growth medium before angiogenic factors (VEGF, bFGF, and PMA) were introduced for an additional 7 days, causing angiogenic sprouts to form. Co-culture with embedded human brain vascular pericytes led to two distinct phenotypes. In one case, endothelial cells sprouted into the matrix but the barrier remained intact. In the other, the endothelium retracted from the walls of microchannels, showed increased leakiness of fluorescent dextran (70 kDa), and endothelial sprouts were absent. In both cases, pericytes were found to associate with endothelial cells, although the frequency was found to be higher in the retracted case. The complex interplay between pericytes, endothelial cells, and angiogenic factors remain to be elucidated, but the system provides the basis for further studies.Figure 3


Microengineering in cardiovascular research: new developments and translational applications.

Chan JM, Wong KH, Richards AM, Drum CL - Cardiovasc. Res. (2015)

Microfluidic devices to study thrombosis. (A) Schematic representation of a collagen hydrogel scaffold embedded with perivascular cells such as human brain vascular pericytes (HBVPs) and microchannels lined with ECs. (B) Whole blood was perfused at 10 µL/min through quiescent (control) and stimulated vessels at time points of 5, 50, 100, 150, and 250 s after initiation of stimulation. The platelets are labelled green with antibodies against platelet-specific glycoprotein IIb (integrin αIIb); an arrow indicates flow direction. Scale, 100 µm. Reproduced with permission from Zheng et al.35.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362405&req=5

CVV049F3: Microfluidic devices to study thrombosis. (A) Schematic representation of a collagen hydrogel scaffold embedded with perivascular cells such as human brain vascular pericytes (HBVPs) and microchannels lined with ECs. (B) Whole blood was perfused at 10 µL/min through quiescent (control) and stimulated vessels at time points of 5, 50, 100, 150, and 250 s after initiation of stimulation. The platelets are labelled green with antibodies against platelet-specific glycoprotein IIb (integrin αIIb); an arrow indicates flow direction. Scale, 100 µm. Reproduced with permission from Zheng et al.35.
Mentions: While single tubes can be easily produced by needle molding, interconnected networks of channels in hydrogels are best generated using lithographic techniques.32 It is worth pointing out the intrinsic merits of using ECM hydrogels here: because they are natural substrates for cell adhesion and can be remodelled by cells (as opposed to PDMS), the endothelium is capable of remodelling the channels and rounding up the sharp corners, producing channels that are still rectangular, but with curved corners.33 These properties enabled the generation of patterned, confluent microvascular networks that are entirely encased by ECM scaffolds.33,34 Zheng et al.35 designed such a perfused microvascular network in collagen scaffolds (Figure 3A) to study angiogenesis, pericyte-endothelial cell interactions, and thrombotic events during an inflammatory response. Vascular networks composed of HUVECs were allowed to mature for 7 days in growth medium before angiogenic factors (VEGF, bFGF, and PMA) were introduced for an additional 7 days, causing angiogenic sprouts to form. Co-culture with embedded human brain vascular pericytes led to two distinct phenotypes. In one case, endothelial cells sprouted into the matrix but the barrier remained intact. In the other, the endothelium retracted from the walls of microchannels, showed increased leakiness of fluorescent dextran (70 kDa), and endothelial sprouts were absent. In both cases, pericytes were found to associate with endothelial cells, although the frequency was found to be higher in the retracted case. The complex interplay between pericytes, endothelial cells, and angiogenic factors remain to be elucidated, but the system provides the basis for further studies.Figure 3

Bottom Line: Microfluidic, cellular co-cultures that approximate macro-scale biology are important tools for refining the in vitro study of organ-level function and disease.Here we review applications of these technologies specific to the cardiovascular field, emphasizing three general categories of use: reductionist vascular models, tissue-engineered vascular models, and point-of-care diagnostics.With continued progress in the ability to purposefully control microscale environments, the detailed study of both primary and cultured cells may find new relevance in the general cardiovascular research community.

View Article: PubMed Central - PubMed

Affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

No MeSH data available.


Related in: MedlinePlus