Activation of polymorphonuclear leukocytes by candidate biomaterials for an implantable glucose sensor.
BACKGROUND
Continuous monitoring of glucose by implantable microfabricated devices offers key advantages over current transcutaneous glucose sensors that limit usability due to their obtrusive nature and risk of infection. A successful sensory implant should be biocompatible and retain long-lasting function. Polymorphonuclear leukocytes (PMN) play a key role in the inflammatory system by releasing enzymes, cytokines, and reactive oxygen species, typically as a response to complement activation. The aim of this study was to perform an in vitro analysis of PMN activation as a marker for biocompatibility of materials and to evaluate the role of complement in the activation of PMN.


METHODS
Fifteen candidate materials of an implantable glucose sensor were incubated in lepirudin-anticoagulated whole blood. The cluster of differentiation molecule 11b (CD11b) expression on PMN was analyzed with flow cytometry and the myeloperoxidase (MPO) concentration in plasma was analyzed with enzyme-linked immunosorbent assay. Complement activation was prevented by the C3 inhibitor compstatin or the C5 inhibitor eculizumab.


RESULTS
Three of the biomaterials (cellulose ester, polyamide reverse osmosis membrane, and polyamide thin film membrane), all belonging to the membrane group, induced a substantial and significant increase in CD11b expression and MPO release. The changes were virtually identical for these two markers. Inhibition of complement with compstatin or eculizumab reduced the CD11b expression and MPO release dose dependently and in most cases back to baseline. The other 12 materials did not induce significant PMN activation.


CONCLUSIONS
Three of the 15 candidate materials triggered PMN activation in a complement-dependent manner and should therefore be avoided for implementation in implantable microsensors.
Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway. andrey.sokolov@medisin.uio.no
Andrey
A
Sokolov
Bernt Christian
BC
Hellerud
John D
JD
Lambris
Erik A
EA
Johannessen
Tom Eirik
TE
Mollnes
D001672:Biocompatible Materials / Q000009:adverse effects*; D001786:Blood Glucose / Q000032:analysis; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008422:Materials Testing; D009504:Neutrophils / Q000276:immunology*; D019736:Prostheses and Implants / Q000009:adverse effects*
D001672:Biocompatible Materials; D001786:Blood Glucose