Analyte flux through chronically implanted subcutaneous polyamide membranes differs in humans and rats
Abstract
The rat is commonly used to evaluate physiological responses of subcutaneous tissue to implanted devices. In vivo longevity of various devices and the biocompatibility of biomaterials depend on how adjacent tissue interacts. How closely the rat model predicts the human response has not been well characterized. The objective of this study was to compare rat and human subcutaneous foreign body responses by monitoring the biochemical environment at a polymer-tissue interface over 8 days using microdialysis. Polyamide microdialysis probes were implanted subcutaneously in humans and rats ( n = 12). Daily microdialysis samples were analyzed for glucose, lactate, pyruvate, glycerol, and urea. Blood glucose was also monitored. Analyte concentrations differed significantly between rats and humans at the implant-tissue interface. There were also qualitative differences in the 8-day trends. For example, over 8 days, microdialysate glucose increased two- to fourfold in humans but decreased in rats ( P < 0.001). This study reveals profound physiological differences at material-tissue interfaces in rats and humans and highlights the need for caution when extrapolating subcutaneous rat biocompatibility data to humans.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The ratio of dialysate glucose to blood glucose was significantly different between rats and humans, indicating differences in relative glucose availability in tissue surrounding an implanted device.
“the ratio of the glucose concentration in the dialysate to that in blood were significantly different between rats and humans indicating differences in the relative glucose availability in the tissue surrounding an implanted device.126”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [126]
Dialysate concentrations of glucose, pyruvate, lactate, glycerol, and urea at a microdialysis probe-tissue interface were significantly different between rats and humans throughout the first 6 days, except for glycerol on day 0.
“The dialysate concentrations were significantly different for all metabolites in rats and humans throughout the first 6 days of the experiment, with the exception of glycerol on day 0.126”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [126]
Human subcutaneous tissue had a high concentration of adipose cells, whereas rat tissue had larger amounts of collagen.
“Histology samplings from human subcutaneous tissue showed a high concentration of adipose cells while rat tissue was characterized with larger amounts of collagen.126”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [126]
These results require caution when extrapolating results from animal models to humans.
“Taken together, these results necessitate careful consideration and caution when extrapolating results from animal models to humans.”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [126]
Cites
THE THEORY AND APPLICATIONS OF THE EXCHANGE OF INERT GAS AT THE LUNGS AND TISSUES
Kety, S. S. (1951) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)07246-1 · Cited by 1,668 · see citing works
Microdialysis—principles and applications for studies in animals and man
Ungerstedt, U. (1991) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1991.tb00459.x · Cited by 813 · see citing works
Self-citationA microdialysis method allowing characterization of intercellular water space in humans
Lönnroth, P., Jansson, P., & Smith, U. (1987) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1987.253.2.e228 · Cited by 634 · see citing works
Methods for reducing biosensor membrane biofouling
Wisniewski, N., & Reichert, M. (2000) · Colloids and Surfaces B: Biointerfaces · doi:10.1016/s0927-7765(99)00148-4 · Cited by 543 · see citing works
Self-citationNeovascularization of synthetic membranes directed by membrane microarchitecture
Brauker, J. H., Carr‐Brendel, V. E., Martinson, L. A., Crudele, J., Johnston, W. D., & Johnson, R. C. (1995) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820291208 · Cited by 517 · see citing works
The physiology of wound healing
Hunt, T. K. (1988) · Annals of Emergency Medicine · doi:10.1016/s0196-0644(88)80351-2 · Cited by 457 · see citing works
Characterization of implantable biosensor membrane biofouling
Wisniewski, N. A., Moussy, F. G., & Reichert, W. M. (2000) · Fresenius Journal of Analytical Chemistry · doi:10.1007/s002160051556 · Cited by 351 · see citing works
Self-citationBlood Flow through Human Adipose Tissue Determined with Radioactive Xenon
Larsen, O. A., Lassen, N. A., & QUAADE, F. (1966) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1966.tb03208.x · Cited by 339 · see citing works
de Vos, P., de Haan, B. J., Wolters, G. H. J., STRUBBE, J. H., & Schilfgaarde, R. V. (1997) · Diabetologia · doi:10.1007/s001250050673 · Cited by 279 · see citing works
Long-term engraftment of hepatocytes transplanted on biodegradable polymer sponges
Mooney, D. J., Sano, K., Kaufmann, P. M., Majahod, K., Schloo, B. L., Vacanti, J. P., & Langer, R. (1997) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(19971205)37:3 · Cited by 233 · see citing works
Self-citationInfluence of the Burn Wound on Local and Systemic Responses to Injury
Wilmore, D. W., AULICK, L. H., Mason, A. D., & Pruitt, B. A. (1977) · Annals of Surgery · doi:10.1097/00000658-197710000-00006 · Cited by 228 · see citing works
Biomaterial–microvasculature interactions
Sieminski, A. L., & Gooch, K. J. (2000) · Biomaterials · doi:10.1016/s0142-9612(00)00149-6 · Cited by 155 · see citing works
Blood circulation in adipose tissue
Rosell, S., & Belfrage, E. (1979) · Physiological Reviews · doi:10.1152/physrev.1979.59.4.1078 · Cited by 151 · see citing works
Moussy, F. G., & Harrison, D. J. (1994) · Analytical Chemistry · doi:10.1021/ac00077a015 · Cited by 146 · see citing works
Bolincier, J., Ungerstedt, U., & Arner, P. (1992) · Diabetologia · doi:10.1007/bf00401374 · Cited by 141 · see citing works
Self-citationFischer, U., Ertle, R., Abel, P., Rebrin, K., Brunstein, E., von Dorsche, H. H., & Freyse, E. (1987) · Diabetologia · doi:10.1007/bf00295878 · Cited by 104 · see citing works
Anomalous diffusion of water in biological tissues
Köpf, M., Corinth, C., Haferkamp, O., & Nonnenmacher, T. F. (1996) · Biophysical Journal · doi:10.1016/s0006-3495(96)79865-x · Cited by 88 · see citing works
Biosensors in the body : continuous in vivo monitoring
Fraser, D. M. (1997) · Wiley eBooks · Cited by 84 · see citing works
Cleek, R. L., Rege, A. A., Denner, L. A., Eskin, S. G., & Mikos, A. G. (1997) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(19970615)35:4 · Cited by 76 · see citing works
Performance of Subcutaneously Implanted Glucose Sensors: A Review
Gerritsen, M., Jansen, J. A., Kros, A., Nolte, R. J. M., & Lutterman, J. A. (1998) · Journal of Investigative Surgery · doi:10.3109/08941939809098031 · Cited by 66 · see citing works
Microdialysis of Glucose in Subcutaneous Adipose Tissue up to 3 Weeks in Healthy Volunteers
Wientjes, K. J. C., Vonk, P., Klei, Y. V.-V., Schoonen, A. J. M., & Kossen, N. W. F. (1998) · Diabetes Care · doi:10.2337/diacare.21.9.1481 · Cited by 58 · see citing works
Evidence for aerobic glycolysis in λ-carrageenan-wounded skeletal muscle
Caldwell, M. D., Shearer, J. D., Morris, A. S., Mastrofrancesco, B., Henry, W., & Albina, J. E. (1984) · Journal of Surgical Research · doi:10.1016/0022-4804(84)90162-8 · Cited by 27 · see citing works
Glucose uptake and flux through phosphofructokinase in wounded rat skeletal muscle
Förster, J., Morris, A. S., Shearer, J. D., Mastrofrancesco, B., Inman, K. C., Lawler, R. G., Bowen, W. D., & Caldwell, M. D. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.256.6.e788 · Cited by 24 · see citing works
Acute cellular interaction with textured surfaces in blood contact
Fujisawa, N., Odell, R. A., Poole-Warren, L. A., Bertram, C., Woodard, J. C., & Schindhelm, K. (2000) · Journal of Biomedical Materials Research · doi:10.1002/1097-4636(20001205)52:3 · Cited by 17 · see citing works
Rosdahl, H. G. (1998) · Figshare · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Biocompatible Materials for Continuous Glucose Monitoring Devices
Nichols, S. P., Koh, A., Storm, W. L., Shin, J. H., & Schoenfisch, M. H. (2013) · Chemical Reviews · doi:10.1021/cr300387j · Cited by 347 · see citing works
Koschwanez, H. E., & Reichert, W. M. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.03.034 · Cited by 181 · see citing works
Self-citationMonitoring biomolecule concentrations in tissue using a wearable droplet microfluidic-based sensor
Nightingale, A. M., Leong, C. L., Burnish, R., Hassan, S.-U., Zhang, Y., Clough, G. F., Boutelle, M. G., Voegeli, D., & Niu, X. (2019) · Nature Communications · doi:10.1038/s41467-019-10401-y · Cited by 155 · see citing works
Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion
Heinemann, L., & Krinelke, L. (2012) · Journal of Diabetes Science and Technology · doi:10.1177/193229681200600429 · Cited by 148 · see citing works
Helton, K. L., Ratner, B. D., & Wisniewski, N. A. (2011) · Journal of Diabetes Science and Technology · doi:10.1177/193229681100500317 · Cited by 125 · see citing works
Self-citationContinuous Glucose Monitoring: 40 Years, What We′ve Learned and What’s Next
Gifford, R. (2013) · ChemPhysChem · doi:10.1002/cphc.201300172 · Cited by 98 · see citing works
White paper on the future of plasma science and technology in plastics and textiles
Cvelbar, U., Walsh, J. L., Černák, M., de Vries, H. W., Reuter, S., Belmonte, T., Corbella, C., Miron, C., Hojnik, N., Jurov, A., et al. (2018) · Plasma Processes and Polymers · doi:10.1002/ppap.201700228 · Cited by 95 · see citing works
Stenken, J. A., Church, M. K., Gill, C. A., & Clough, G. F. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9163-7 · Cited by 88 · see citing works
Streijger, F., So, K., Manouchehri, N., Tigchelaar, S., Lee, J. H. T., Okon, E. B., Shortt, K., Kim, S.-E., McInnes, K. A., Cripton, P. A., et al. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2017.5034 · Cited by 70 · see citing works
El‐Ghoul, Y., Blanchemain, N., Laurent, T., Campagne, C., Achari, A. E., Roudeslı, S., Morcellet, M., Martel, B., & Hildebrand, H.-F. (2008) · Acta Biomaterialia · doi:10.1016/j.actbio.2008.02.019 · Cited by 63 · see citing works
Adult adipose-derived stem cell attachment to biomaterials
Prichard, H. L., Reichert, W. M., & Klitzman, B. M. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.09.012 · Cited by 50 · see citing works
Self-citationWhyte, W., Goswami, D., Wang, S. X., Fan, Y., Ward, N. A., Levey, R. E., Beatty, R., Robinson, S. T., Sheppard, D., O’Connor, R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32147-w · Cited by 47 · see citing works
Soft robot–mediated autonomous adaptation to fibrotic capsule formation for improved drug delivery
Beatty, R., Mendez, K. L., Schreiber, L. H. J., Tarpey, R., Whyte, W., Fan, Y., Robinson, S. T., O’Dwyer, J., Simpkin, A. J., Tannian, J., et al. (2023) · Science Robotics · doi:10.1126/scirobotics.abq4821 · Cited by 47 · see citing works
IFATS Collection: Adipose-Derived Stromal Cells Improve the Foreign Body Response
Prichard, H. L., Reichert, W. M., & Klitzman, B. M. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0140 · Cited by 42 · see citing works
Self-citationBiocompatibility of Electrochemical Glucose Sensors Implanted in the Subcutis of Pigs
Kvist, P. H., Iburg, T. M., Bielecki, M., Gerstenberg, M., Buch‐Rasmussen, T., Hasselager, E., & Jensen, H. E. (2006) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2006.8.463 · Cited by 38 · see citing works
Okon, E. B., Streijger, F., Lee, J. H. T., Anderson, L. M., Russell, A. K., & Kwon, B. K. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2013.2956 · Cited by 38 · see citing works
Ultraslow microdialysis and microfiltration for in-line, on-line and off-line monitoring
Korf, J., Huinink, K. D., & Posthuma‐Trumpie, G. A. (2010) · Trends in biotechnology · doi:10.1016/j.tibtech.2009.12.005 · Cited by 37 · see citing works
Clausen, T. S., Kaastrup, P., & Stallknecht, B. (2009) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2009.0058 · Cited by 36 · see citing works
BARTÁK, V., Vybíral, S., Papežová, H., Dostálová, I., Pacák, K., & Nedvidkova, J. (2004) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2004.01344.x · Cited by 33 · see citing works
The use of wound healing assessment methods in psychological studies: A review and recommendations
Koschwanez, H. E., & Broadbent, E. (2010) · British Journal of Health Psychology · doi:10.1348/135910710x524633 · Cited by 33 · see citing works
Heise, H. M., Damm, U., Bodenlenz, M., Kondepati, V. R., Köhler, G., & Ellmerer, M. (2007) · Journal of Biomedical Optics · doi:10.1117/1.2714907 · Cited by 32 · see citing works
Ekberg, N. R., Wisniewski, N., Brismar, K., & Ungerstedt, U. (2005) · Clinica Chimica Acta · doi:10.1016/j.cccn.2005.03.033 · Cited by 31 · see citing works
Self-citationThe use of CD47-modified biomaterials to mitigate the immune response
Tengood, J. E., Levy, R. J., & Stachelek, S. J. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216647130 · Cited by 30 · see citing works
Krysiak, Z. J., Gawlik, M. Z., Knapczyk‐Korczak, J., Kaniuk, Ł., & Stachewicz, U. (2020) · Materials · doi:10.3390/ma13081974 · Cited by 29 · see citing works
Microdialysis-Coupled Enzymatic Microreactor for in Vivo Glucose Monitoring in Rats
Moon, B., de Vries, M. G., CORDEIRO, C. A., Westerink, B. H. C., & Verpoorte, E. M. J. (2013) · Analytical Chemistry · doi:10.1021/ac402414m · Cited by 26 · see citing works
Clausen, T. S., Kaastrup, P., & Stallknecht, B. M. (2009) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2009.03.001 · Cited by 25 · see citing works
Rigla, M., Pons, B., Rebasa, P., Luna, A., del Pozo, F. J. D., Caixàs, A., Villaplana, M., Subías, D., Bella-Cueto, M. R., & Combalía, N. (2018) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2017.0321 · Cited by 20 · see citing works
Bonato, L., Taleb, N., Gingras, V., Messier, V., Gobeil, F., Ménard, J., Ardilouze, J., & RABASA-LHORET, R. P. R. (2018) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2018.0110 · Cited by 17 · see citing works
Ekberg, N. R., Ungerstedt, U., & Brismar, K. (2004) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2004.00424.x · Cited by 17 · see citing works
Self-citationMou, X., Lennartz, M. R., Loegering, D. J., & Stenken, J. A. (2011) · Journal of Diabetes Science and Technology · doi:10.1177/193229681100500316 · Cited by 17 · see citing works
Damm, U., Kondepati, V. R., & Heise, H. M. (2006) · Vibrational Spectroscopy · doi:10.1016/j.vibspec.2006.07.011 · Cited by 16 · see citing works
Mechanotherapy: Modulating immune cell function in tissue regeneration and fibrosis
Ward, N. A., Prendeville, H., Wallace, E. J., Shokrani, P., Trask, L., Dillon, R., Beatty, R., Roche, E. T., Duffy, G. P., & Dolan, E. B. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.08.048 · Cited by 10 · see citing works
Preclinical Performance Evaluation of Percutaneous Glucose Biosensors
Soto, R. J., & Schoenfisch, M. H. (2015) · Journal of Diabetes Science and Technology · doi:10.1177/1932296815590628 · Cited by 8 · see citing works
Ekberg, N. R., Brismar, K., Malmstedt, J., Hedblad, M., Adamson, U., Ungerstedt, U., & Wisniewski, N. A. (2010) · Journal of Diabetes Science and Technology · doi:10.1177/193229681000400505 · Cited by 8 · see citing works
Self-citationBioluminescence Imaging of Glucose in Tissue Surrounding Polyurethane and Glucose Sensor Implants
Prichard, H. L., Schroeder, T., Reichert, W. M., & Klitzman, B. M. (2010) · Journal of Diabetes Science and Technology · doi:10.1177/193229681000400504 · Cited by 8 · see citing works
Self-citationHamrangsekachaee, M., Baumann, H. J., Pukale, D. D., Shriver, L. P., & Leipzig, N. D. (2022) · ACS Applied Bio Materials · doi:10.1021/acsabm.2c00017 · Cited by 7 · see citing works
Stenken, J. A. (2006) · Encyclopedia of Medical Devices and Instrumentation · doi:10.1002/0471732877.emd330 · Cited by 6 · see citing works
Chapter 2.1 New methodological aspects of microdialysis
Kehr, J. (2006) · Handbook of behavioral neuroscience · doi:10.1016/s1569-7339(06)16007-5 · Cited by 5 · see citing works
Cardoso, G. B. C., Chacon, E. L., Maia, L. R. B., Zavaglia, C. A. D. C., & da Cunha, M. R. (2018) · Materials Research · doi:10.1590/1980-5373-mr-2018-0491 · Cited by 4 · see citing works
Stable use of biosensors at the sample interface
Gargiuli, J. F., Gill, A., Lillie, G. C., Schoenleber, M., Pearson, J. E., Kyriakou, G., & Vadgama, P. M. (2005) · Elsevier eBooks · doi:10.1533/9781845690809.1.103 · Cited by 3 · see citing works
Analysis: Mouse Models of Glucose Sensor Biocompatibility
Friedl, K. E. (2005) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2005.7.738 · Cited by 3 · see citing works
Huinink, K. D., & Korf, J. (2006) · Handbook of behavioral neuroscience · doi:10.1016/s1569-7339(06)16012-9 · Cited by 2 · see citing works
Stenken, J. A. (2009) · doi:10.1002/9780470567319.ch6 · Cited by 2 · see citing works
Sokolov, A. (2012) · NORA - Norwegian Open Research Archives · Cited by 2 · see citing works
Subcutaneous glucose biosensor failure – a fuzzy fault tree analysis approach
Siontorou, C. G., & Batzias, F. A. (2014) · International Journal of Design & Nature and Ecodynamics · doi:10.2495/dne-v9-n2-149-164 · Cited by 1 · see citing works
Koschwanez, H. E. (2009) · DukeSpace (Duke University) · Cited by 1 · see citing works
Treatment of textile surfaces by plasma technology for biomedical applications
Labay, C. (2014) · doi:10.5821/dissertation-2117-95422 · Cited by 1 · see citing works
Chapter 7.2 Transport of glucose to a probe in adipose tissue
Wientjes, K., Hoogenberg, K., & Schoonen, A. J. M. (2006) · Handbook of behavioral neuroscience · doi:10.1016/s1569-7339(06)16034-8
Development of a continuous glucose monitor based on microfluidics
Moon, B. (2012) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Slow microfiltration or slow microdialysis to versatile biomonitoring
Huinink, K. D. (2009) · University of Groningen research database (University of Groningen / Centre for Information Technology)
- Authors
- Wisniewski, N., Rajamand, N., Adamsson, U., Lins, P. E., Reichert, W. M., Klitzman, B., & Ungerstedt, U.
- Affiliations
- Departments of Biomedical Engineering and
- Department of Physiology and Pharmacology, Karolinska Institute, Stockholm S-17177; and
- Danderyds sjukhus (SE)
- Duke University (US)
- Karolinska Institutet (SE)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2002-06-01
- Volume
- 282
- Issue
- 6
- Pages
- E1316-E1323
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2161380946
- Cited by
- 50
- References
- 25
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 3
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK54932)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Health Sciences › Medicine › Surgery › Surgical Sutures and Adhesives
- Keywords
- polyamide membranes, biocompatibility, human-rat comparison, microdialysis, implant-tissue interface, glucose, lactate, pyruvate, glycerol, urea, blood glucose, biomaterials
- MeSH terms
- Adult, Animals, Biocompatible Materials, Blood Glucose, Glucose, Glycerol, Humans, Male, Membranes, Artificial, Microscopy, Electron, Nylons, Species Specificity, Time Factors, Urea, Rats, Sprague-Dawley, Microdialysis, Pyruvic Acid, Lactic Acid, Prostheses and Implants, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review