Journal
BIOMATERIALS
Volume 34, Issue 3, Pages 621-630Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.10.012
Keywords
Biomaterial; Inflammation; Complement; Biocompatibility; Microspheres; Alginate
Funding
- Central Norway Regional Health Authority
- European Commission
- Slovak Research and Development Agency [APVV-0486-10]
- EFDS New Horizons grant
- National Institutes of Health [A1068730]
- Chicago Diabetes Project
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The cytokine-inducing potential of various microspheres were evaluated in a short-time screening assay of lepirudin-anticoagulated human whole blood utilizing the Bio-Plex Human cytokine 27-plex system. The inflammatory cytokines IL-1 beta, TNF and IL-6; the anti-inflammatory mediators IL-1ra and IL-10; the chemokines IL-8, MIP-1 alpha and MCP-1; and the growth factor VEGF were induced by polycation (poly-L-lysine or poly(methylene-co-guanidine)) containing microspheres. Alginate microspheres without polycations did not induce the corresponding cytokine panel, nor did soluble alginate. By inhibiting complement C3 using compstatin analog CP20, a total inhibition of complement activation as well as the inflammatory mediators was achieved, indicating that complement activation alone was responsible for the induced cytokines. A strong deposition of C3c on the poly-L-lysine containing surface, while not on the microspheres lacking polycations, also points to the formation of C3 convertase as involved in the biomaterial-induced cytokine induction. These results show that complement is responsible for the induction of cytokines by polycation containing microspheres. We point to complement as an important initiator of inflammatory responses to biomaterials and the lepirudin anticoagulated whole blood assay as an important tool to identify the most tolerable and safe materials for implantation to humans. (C) 2012 Elsevier Ltd. All rights reserved.
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