Surface-attached PEO in the form of activated pluronic with immobilized factor H reduces both coagulation and complement activation in a whole-blood model

被引:33
作者
Andersson, J
Bexborn, F
Klinth, J
Nilsson, B
Ekdahl, KN [1 ]
机构
[1] Uppsala Univ, Div Clin Immunol, Uppsala, Sweden
[2] Kalmar, Dept Chem & Biomed Sci, Kalmar, Sweden
关键词
blood compatibility; coagulation; complement; factor H; regulator of complement activation (RCA);
D O I
10.1002/jbm.a.30377
中图分类号
R318 [生物医学工程];
学科分类号
0831 [生物医学工程];
摘要
In the present work we have bound Pluronic (TM), a class of triblock copolymers consisting of a block of polypropylene oxide (PPO) surrounded on each side by polyethylene oxide (PEO) blocks, to polystyrene surfaces and investigated the thrombogenicity and complement activation of this construct upon exposure to whole blood. The surface was highly inert towards coagulation, unfortunately at the expense of increased complement activation. We, therefore, as an alternative approach, used End-Group Activated Pluronic to conjugate factor H, a regulator of complement activation (RCA), to the surface. The bound factor H did not detach from the surface upon incubation with human serum. Furthermore, factor H bound in a physiological conformation could to a significant degree attenuate complement activation at the Pluronic (TM) surface. Thus, we have created a hybrid surface in which the coagulation-inert properties of the original Pluronic (TM) are supplemented with a specific complement-inhibitory effect. Medical device technology includes numerous potential applications for crosslinkers that are capable of specifically binding biomolecules to surfaces with retained activity. These applications include coupling of functional biomolecules to biomedical devices such as stents and grafts. The biomolecule may be an RCA, antibody, or other beneficial ligand. (c) 2005 Wiley Periodicals, Inc.
引用
收藏
页码:25 / 34
页数:10
相关论文
共 41 条
[1]
PREVENTION OF PROTEIN ADSORPTION AND PLATELET-ADHESION ON SURFACES BY PEO PPO PEO TRIBLOCK COPOLYMERS [J].
AMIJI, M ;
PARK, K .
BIOMATERIALS, 1992, 13 (10) :682-692
[2]
Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro [J].
Andersson, J ;
Sanchez, J ;
Ekdahl, KN ;
Elgue, G ;
Nilsson, B ;
Larsson, R .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2003, 67A (02) :458-466
[3]
Binding of a model regulator of complement activation (RCA) to a biomaterial surface: surface-bound factor H inhibits complement activation [J].
Andersson, J ;
Larsson, R ;
Richter, R ;
Ekdahl, KN ;
Nilsson, B .
BIOMATERIALS, 2001, 22 (17) :2435-2443
[4]
SECONDARY STRUCTURE OF A COMPLEMENT CONTROL PROTEIN MODULE BY 2-DIMENSIONAL H-1-NMR [J].
BARLOW, PN ;
BARON, M ;
NORMAN, DG ;
DAY, AJ ;
WILLIS, AC ;
SIM, RB ;
CAMPBELL, ID .
BIOCHEMISTRY, 1991, 30 (04) :997-1004
[5]
The effect of substrate molecular mobility on surface induced immune complement activation and blood plasma coagulation [J].
Berglin, M ;
Andersson, M ;
Sellborn, A ;
Elwing, H .
BIOMATERIALS, 2004, 25 (19) :4581-4590
[6]
PROTEIN THIOLATION AND REVERSIBLE PROTEIN-PROTEIN CONJUGATION - N-SUCCINIMIDYL 3-(2-PYRIDYLDITHIO)PROPIONATE, A NEW HETEROBIFUNCTIONAL REAGENT [J].
CARLSSON, J ;
DREVIN, H ;
AXEN, R .
BIOCHEMICAL JOURNAL, 1978, 173 (03) :723-737
[7]
SEQUENCE POLYMORPHISM OF HUMAN-COMPLEMENT FACTOR-H [J].
DAY, AJ ;
WILLIS, AC ;
RIPOCHE, J ;
SIM, RB .
IMMUNOGENETICS, 1988, 27 (03) :211-214
[8]
DISCIPIO RG, 1992, J IMMUNOL, V149, P2592
[9]
GENERATION OF IC3 AT THE INTERFACE BETWEEN BLOOD AND GAS [J].
EKDAHL, KN ;
NILSSON, B ;
PEKNA, M ;
NILSSON, UR .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1992, 35 (01) :85-91
[10]
FEARON DT, 1977, J IMMUNOL, V119, P1248