HemocompatibilityArtificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/ or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.

Promising cell therapies using mesenchymal stem cells (MSCs) is proposed for stroke patients. Therefore, we aimed to efficiently accumulate human MSC (hMSC) to damaged brain area to improve the therapeutic effect using poly(ethylene glycol) (PEG)‐conjugated phospholipid (PEG‐lipid) carrying an oligopeptide as a ligand, specific for E‐selectin which is upregulated on activated endothelial cells under hypoxia‐like stroke. Here we synthesized E‐selectin‐binding oligopeptide (ES‐bp) conjugated with PEG spacer having different molecular weights from 1 to 40 kDa. We found that ES‐bp can be immobilized onto the hMSC surface through PEG‐lipid without influence on cell growth and differentiation into adipocytes and osteocytes, respectively. It is also possible to control the immobilization of ES‐bp on hMSC surface (<108 ES‐bp per cell). Immobilized ES‐bp can be continuously immobilized at the outside of cell membrane when PEG‐lipids with PEG 5 and 40 kDa were used. In addition, the modified hMSC can specifically attach onto E‐selectin‐immobilized surface as a model surface of activated endothelium in human blood, indicating the sufficient number of immobilized ES‐bp onto hMSC. Thus, this technique is one of the candidates for hMSC accumulation to cerebral infarction area. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1779–1792, 2019.

No abstract

Microencapsulation of islets can protect against immune reactions from the host immune system after transplantation. However, sufficient numbers of islets cannot be transplanted due to the increase of the size and total volume. Therefore, thin and stable polymer membranes are required for the microencapsulation. Here, we undertook the cell microencapsulation using poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) and layer-by-layer membrane of multiple-arm PEG. In order to examine the membrane stability, we used different molecular weights of 4-arm PEG (10k, 20k and 40k)-Mal to examine the influence on the polymer membrane stability. We found that the polymer membrane made of 4-arm PEG(40k)-Mal showed the highest stability on the cell surface. Also, the polymer membrane did not disturb the insulin secretion from beta cells.

Organ transplantation leads to damage of the endothelial glycocalyx of the transplanted organ, and the activated endothelial surface induces thromboinflammation. The result is dysfunction of the transplanted organ, known as ischemia reperfusion injury (IRI). Long‐term graft survival strongly depends on the regulation of IRI. Here the aim is to reconstruct the glycocalyx to regulate blood activation during IRI. Heparin‐conjugated lipid (fHep‐lipid) is synthesized with 0.6, 1.8, 2.7, 4.5, or 8.0 fragmented heparins per lipid to compare their anticoagulation activity. First, liposome and cells are modified with each fHep‐lipid and the surface properties are evaluated. Then the hemocompatibility of the modified human mesenchymal stem cells (hMSCs) is examined in a loop model using human blood. The antithrombin‐binding capacity and anti‐factor Xa activity of the fHep‐lipids depend on the number of conjugated heparins, with efficacy increasing with increasing number of heparins. The modified liposomes are highly negatively charged and show strong anti‐factor Xa activity. In addition, the cell surfaces of human erythrocytes and hMSCs can be uniformly modified with fHep‐lipid. The whole blood studies reveal that fHep‐lipid on hMSCs can prevent generation of thrombin–antithrombin complexes, coagulation markers, and platelet aggregation, whereas unmodified hMSCs trigger activation of the platelet and coagulation systems.