A new method for the covalent binding of heparin to artificial surfaces has been developed. The heparinized surface releases insignificant amounts of heparin and can be regarded as stable. The blood contact properties as studied in vitro revealed that the surface was highly thromboresistant in terms of reduced platelet adhesion, surface catalyzed adsorption and inhibition of thrombin and capacity to prevent clotting of nonanticoagulated blood.
The effect of heparin ionically linked to chitosan on the stimulation of re-epithelialisation of full thickness wounds in human skin was investigated in an in vitro model. After seven days of incubation, heparin-chitosan gel stimulated 9/10 of the full thickness wounds to re-epithelialise compared with only 3/10 of the wounds that were covered with chitosan gel or membrane, and none of the wounds incubated without gel or membrane or with heparin solution alone. Both dermal and epidermal cells were viable after the incubation time. Furthermore, the stimulatory effect of the heparin-chitosan complexes depended on the concentration of heparin in the complex. We hypothesise that these effects are caused by stabilisation and activation of growth factors that bind to immobilised heparin.
Covalent end point surface heparinization appears to have a great impact on both in vitro and in vivo bacterial colonization of central venous catheters. Such heparinization can be a practical and economical approach to the prevention of catheter-associated bacteremia or fungemia.
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