1.
Engberg, Anna, 1982-, et al.
(author)
BLOOD PROTEIN-POLYMER ADSORPTION FINGERPRINTING:IMPLICATIONS FOR UNDERSTANDING HEMOCOMPATIBILITYAND FOR BIOMATERIAL DESIGN
Other publication (other academic/artistic) abstract
Within seconds after an artificial material has been implanted into the blood thesurface will be covered by adsorbed plasma proteins. The composition of theprotein layer is determined by the physical-chemical properties of the surface. Asthe layer itself will become the new interface between the material and blood, itis of major importance for the hemocompatibility. In this project we have studiedthe adsorption of proteins to a model material (polystyrene, PS) with the peptidemass fingerprint technique (PMF) analyzed on a Matrix Assisted LaserDesorption/Ionization Time-of-Flight (MALDI-TOF). To further be able to studythe adsorption of plasma proteins to polymer surfaces, we have synthesized 33new polymer compositions with variable surface properties. Six of thosepolymers were selected and their protein binding ability was determined as wellas quantification of adsorption of 20 plasma proteins to the surface of thepolymers. Our results showed that fourteen high abundant plasma proteins werepositively identified on the PS-surface by MALDI-TOF. Further, the resultsshowed that the synthesized polymers had very distinctive adsorption patterns,with enrichment of different proteins after incubation in plasma and serum. Oneof the polymers was shown to adsorb large amounts of the complementactivating recognition protein C1q, which makes this polymer to a potentialactivating surface. Two of the polymers showed a clear enrichment of thecomplement regulating protein vitronectin as well as two apolipoproteins (AI andAIV) to the surface of the polymers, while some of the polymers bound proteinsapproximately in correlation to the concentration found in plasma.
2.
Engberg, Anna E., 1982-, et al.
(author)
EVALUATION OF THE HEMOCOMPATIBILITY OF NOVEL POLYMERIC MATERIALS
Other publication (other academic/artistic) abstract
When a biomaterial surface comes in contact with blood an immediate adsorption of plasma proteins to the surface will occur, and the cascade systems in the blood, such as the complement, coagulation and contact system, will be activated to various degrees. The intensity of this reaction will determine the hemocompatibility of the materials. Here we present an evaluation of the link between the composition, the physico-chemical properties and the protein adsorption properties of six newly synthesized polymers (P1-P6) and the hemocompatibility.The hemocompatibility of the polymeric surfaces was evaluated in human blood plasma and whole blood. Commercially available polyvinylchloride (PVC) was used as reference material. The hemocompatibility of the polymeric surfaces was evaluated with regard to complement activation (C3a and sC5-9 generation) and coagulation activation (platelet loss and TAT-formation) and cytokine productions (27 analytes in multiplex assay) after contact with whole blood. Contact activation was quantified by analyses of FXIIa-C1INH, FXIa-C1INH, and kallikrein-C1INH complexes.Polymers P2 (p<0.05 for C3a), P3, P5 and P6 showed less complement activation, and polymers P1 and P4 (p<0.05 for platelet loss), as well as P5 and P6 showed less coagulation activation compared with reference PVC. Polymers P1-P3 induced activation of the contact system, P3 being the most potent. Secretion of 17 cytokines including chemokines and growth factors were differentially influenced by the polymers, P1 and P3 being significantly (p<0.05) more compatible for five of the analytes.Collectively these data demonstrate that the composition of the polymers clearly leads to different biological properties as a consequence of distinctive physico-chemical properties and protein adsorption patterns.1
3.
Nilsson, Per, et al.
(author)
IMMOBILIZATION OF APYRASE CREATES AN ANTITHROMBOTIC BIOMATERIAL SURFACE
Other publication (other academic/artistic) abstract
Blood incompatibility reactions caused by surfaces often involve platelet activation and subsequent platelet-initiated activation of the coagulation and complement cascades. The goal of this proof-of-principle study was to immobilize apyrase on a biomaterial surface in order to develop an enzymatically active surface that would have the capacity to inhibit platelet activation by degradating ADP. We were able to immobilize apyrase on a polystyrene surface with preservation of the enzymatic activity. We then analyzed the hemocompatibility of the apyrase surface and of control surfaces (serum albumin, avidin, polystyrene, and glass) by incubation with platelet-rich plasma (PRP) or whole blood. Monitoring of markers of platelet, coagulation, and complement activation and staining of the surfaces revealed decreased levels of platelet and coagulation activation parameters on the apyrase surface. The level of complex formation between antithrombin and thrombin or factor XIa and the extent of the platelet loss were significantly lower on the apyrase surface than on any of the control surfaces. No significant differences were seen in complement activation (C3a levels). Staining of the apyrase surface revealed low platelet adherence and no formation of granulocyte-platelet complexes. These results demonstrate that it is possible to create an anti-thrombotic surface targeting the ADP amplification of platelet activation by immobilizing apyrase.
