The study of inflammatory bowel disease, including Ulcerative Colitis and Crohn's Disease, has relied largely upon the use of animal or cell culture models; neither of which can represent all aspects of the human pathophysiology. Presented herein is a dual flow microfluidic device which holds full thickness human intestinal tissue in a known orientation. The luminal and serosal sides are independently perfused ex vivo with nutrients with simultaneous waste removal for up to 72 h. The microfluidic device maintains the viability and integrity of the tissue as demonstrated through Haematoxylin & Eosin staining, immunohistochemistry and release of lactate dehydrogenase. In addition, the inflammatory state remains in the tissue after perfusion on the device as determined by measuring calprotectin levels. It is anticipated that this human model will be extremely useful for studying the biology and testing novel interventions in diseased tissue.

1.
M. Z.
Cader
and
A.
Kaser
, “
Recent advances in inflammatory bowel disease: Mucosal immune cells in intestinal inflammation
,”
Gut
62
(
11
),
1653
1664
(
2013
).
2.
S.
Danese
, “
New therapies for inflammatory bowel disease: From the bench to the bedside
,”
Gut
61
(
6
),
918
932
(
2012
).
3.
S. G.
Nugent
,
D.
Kumar
,
D. S.
Rampton
, and
D. F.
Evans
, “
Intestinal luminal pH in inflammatory bowel disease: Possible determinants and implications for therapy with aminosalicylates and other drugs
,”
Gut
48
(
4
),
571
577
(
2001
).
4.
S. B.
Hanauer
, “
Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities
,”
Inflammatory Bowel Dis.
12
(
5
),
S3
S9
(
2006
).
5.
F.
Shanahan
, “
Probiotics and inflammatory bowel disease: Is there a scientific rationale?
,”
Inflammatory Bowel Dis.
6
(
2
),
107
115
(
2000
).
6.
K.
Tsilingiri
,
T.
Barbosa
,
G.
Penna
 et al, “
Probiotic and postbiotic activity in health and disease: Comparison on a novel polarised ex-vivo organ culture model
,”
Gut
61
(
7
),
1007
1015
(
2012
).
7.
A. N.
Ananthakrishnan
,
S. C.
Cheng
,
T.
Cai
 et al, “
Serum inflammatory markers and risk of colorectal cancer in patients with inflammatory bowel diseases
,”
Clin. Gastroenterol. Hepatol.
12
(
8
),
1342-8.e1
(
2014
).
8.
A.
Boleij
and
H.
Tjalsma
, “
Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer
,”
Biol. Rev.
87
(
3
),
701
730
(
2012
).
9.
S. H.
Itzkowitz
and
D. H.
Present
Consensus conference: Colorectal cancer screening and surveillance in inflammatory bowel disease
,”
Inflammatory Bowel Dis.
11
(
3
),
314
321
(
2005
).
10.
J. K.
Triantafillidis
,
G.
Nasioulas
, and
P. A.
Kosmidis
, “
Colorectal cancer and inflammatory bowel disease: Epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies
,”
Anticancer Res.
29
(
7
),
2727
2737
(
2009
).
11.
B.
Chassaing
,
J. D.
Aitken
,
M.
Malleshappa
, and
M.
Vijay-Kumar
, “
Dextran sulfate sodium (DSS)-induced colitis in mice
,”
Curr. Protoc. Immunol.
104
(15.25),
15.25.1
15.25.14
(
2014
).
12.
C. R.
Kleiveland
,
L. T. O.
Hult
,
S.
Spetalen
 et al, “
The noncommensal Bacterium Methylococcus capsulatus (Bath) ameliorates dextran sulfate (sodium salt)-induced ulcerative colitis by influencing mechanisms essential for maintenance of the colonic barrier function
,”
Appl. Environ. Microbiol.
79
(
1
),
48
56
(
2013
).
13.
P. S.
Dulai
,
C. A.
Siegel
,
J.-F.
Colombel
,
W. J.
Sandborn
, and
L.
Peyrin-Biroulet
, “
Systematic review: Monotherapy with antitumour necrosis factor α agents versus combination therapy with an immunosuppressive for IBD
,”
Gut
63
(
12
),
1843
1853
(
2014
).
14.
C. J.
Bettinger
and
J. T.
Borenstein
, “
Biomaterials-based microfluidics for engineered tissue constructs
,”
Soft Matter
6
(
20
),
4999
5015
(
2010
).
15.
H. J.
Kim
and
D. E.
Ingber
, “
Gut-on-a-chip microenvironment induces human intestinal cells to undergo villus differentiation
,”
Integr. Biol.
5
(
9
),
1130
1140
(
2013
).
16.
A.
Ponder
and
M. D.
Long
, “
A clinical review of recent findings in the epidemiology of inflammatory bowel disease
,”
Clin. Epidemiol.
5
,
237
247
(
2013
).
17.
H. J.
Kim
,
D.
Huh
,
G.
Hamilton
, and
D. E.
Ingber
, “
Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow
,”
Lab Chip
12
(
12
),
2165
2174
(
2012
).
18.
L. L.
Clarke
, “
A guide to Ussing chamber studies of mouse intestine
,”
Am. J. Physiol. Gastrointest. Liver Physiol.
296
(
6
),
G1151
G1166
(
2009
).
19.
K. W.
Lomasney
and
N. P.
Hyland
, “
The application of Ussing chambers for determining the impact of microbes and probiotics on intestinal ion transport
,”
Can. J. Physiol. Pharmacol.
91
(
9
),
663
670
(
2013
).
20.
E.
Rodrigues
,
L.
Slobbe
,
M.
Schultz
, and
G.
Butt
, “
Chronic exposure to microbial stimuli affects the development of the intestinal epithelium in human colonic enteroids
,”
FASEB J.
29
,
26
28
(
2015
).
21.
I.
Maschmeyer
,
A. K.
Lorenz
,
K.
Schimek
 et al, “
A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents
,”
Lab Chip
15
(
12
),
2688
2699
(
2015
).
22.
M.
Baker
, “
Tissue models: A living system on a chip
,”
Nature
471
(
7340
),
661
665
(
2011
).
23.
S.
Hattersley
,
D.
Sylvester
,
C.
Dyer
,
N.
Stafford
,
S.
Haswell
, and
J.
Greenman
, “
A microfluidic system for testing the responses of head and neck squamous cell carcinoma tissue biopsies to treatment with chemotherapy drugs
,”
Ann. Biomed. Eng.
40
(
6
),
1277
1288
(
2012
).
24.
S. M.
Hattersley
,
C. E.
Dyer
,
J.
Greenman
, and
S. J.
Haswell
, “
Development of a microfluidic device for the maintenance and interrogation of viable tissue biopsies
,”
Lab Chip
8
(
11
),
1842
1846
(
2008
).
25.
S. M.
Hattersley
,
J.
Greenman
, and
S. J.
Haswell
, “
Study of ethanol induced toxicity in liver explants using microfluidic devices
,”
Biomed. Microdevices
13
(
6
),
1005
1014
(
2011
).
26.
S. M.
Hattersley
,
J.
Greenman
, and
S. J.
Haswell
, “
The application of microfluidic devices for viral diagnosis in developing countries
,”
Methods Mol. Biol.
949
,
285
303
(
2013
).
27.
E.
Cuevas
,
D. B.
Jones
, and
D. H.
Wright
, “
Immunohistochemical detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues
,”
J. Pathol.
169
(
4
),
477
478
(
1993
).
28.
R.
Najafi
and
S. M.
Bernard
,
“Use of physiologically balanced, ionized, acidic solution in wound healing
,” U.S. patent US6426066 B1 (30 July
2002
).
29.
J.
Westerhout
,
E.
van de Steeg
,
D.
Grossouw
 et al, “
A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices
,”
Eur. J. Pharm. Sci.
63
,
167
177
(
2014
).
30.
A.
Webster
,
C. E.
Dyer
,
S. J.
Haswell
, and
J.
Greenman
, “
A microfluidic device for tissue biopsy culture and interrogation
,”
Anal. Methods
2
(
8
),
1005
1007
(
2010
).
31.
J.
Woods
,
P. T.
Docker
,
C. E.
Dyer
,
S. J.
Haswell
, and
J.
Greenman
, “
On-chip integrated labelling, transport and detection of tumour cells
,”
Electrophoresis
32
(
22
),
3188
3195
(
2011
).
32.
M.
Schaubeck
,
T.
Clavel
,
J.
Calasan
 et al, “
Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence
,”
Gut
65
(
2
),
225
237
(
2016
).
33.
D.
Sylvester
,
S. M.
Hattersley
,
N. D.
Stafford
,
S. J.
Haswell
, and
J.
Greenman
, “
Development of microfluidic-based analytical methodology for studying the effects of chemotherapy agents on cancer tissue
,”
Current Analyt. Chem.
9
(
1
),
2
8
(
2013
).
34.
D. T.
Rubin
, “
The rationale and growth of advanced training in inflammatory bowel disease
,”
Gastroenterology
148
(
4
),
696
700
(
2015
).
35.
S. C.
Ng
,
C. N.
Bernstein
,
M. H.
Vatn
 et al, “
Geographical variability and environmental risk factors in inflammatory bowel disease
,”
Gut
62
(
4
),
630
649
(
2013
).
36.
E.-M.
Materne
,
I.
Maschmeyer
,
A. K.
Lorenz
 et al, “
The multi-organ chip - A microfluidic platform for long-term multi-tissue coculture
,”
J. Vis. Exp.
98
,
e52526
(
2015
).
37.
A. D.
van der Meer
and
A.
van den Berg
, “
Organs-on-chips: breaking the in vitro impasse
,”
Integr. Biol.
4
(
5
),
461
470
(
2012
).
38.
A.
Williamson
,
S.
Singh
,
U.
Fernekorn
, and
A.
Schober
, “
The future of the patient-specific body-on-a-chip
,”
Lab Chip
13
(
18
),
3471
3480
(
2013
).
39.
P.
Loskill
,
S. G.
Marcus
,
A.
Mathur
,
W. M.
Reese
, and
K. E.
Healy
, “
μOrgano: A Lego™ like plug & play system for modular multi-organ-chips
,”
PLoS One
10
(
10
),
e0139587
(
2015
).
You do not currently have access to this content.