Research: Blood-Biomaterial Interactions and Biocompatibility.


Blood Biocompatibility Catastrophe [1]:

Despite some fifty years of research, all materials used in medical applications today cause thrombotic and/or inflammatory reactions, necessitating short-term or long-term antiplatelet therapy that is costly and dangerous to the patient.


Blood-Biomaterial Interactions in a Nutshell: molecular mechanism of incompatibility.

Foreign materials interact with the body, activating the three coupled defense systems: coagulation, inflammation, complement: 

Thrombosis: Vessel (or stent, or heart valve, etc.)  occlusion and emboli.

Inflammation, Complement activation: Activated platelets, macrophages, leukocytes, cytokine production, systemic damage.

A key role in this process is thought to be played by plasma proteins that adsorb on the implant surfaces and by platelets that in one way or another participate in all three systems [2].

The figure is adapted from [2].


Blood proteins normally do not interact with blood cells, but when they adsorb to foreign surfaces, they undergo conformational changes[3] that expose cryptic sequences. Below, this is shown using platelet activation at foreign surfaces as an example:

Left: Platelets (shown in the left drawing as grey circles) circulate in blood in a resting state and do not interact with blood proteins. 

Middle: Adsorption of blood proteins to the biomaterial surface is thought to alter their conformation.

Right: Adsorbed proteins are then thought to activate platelets.

Platelet activation leads to changes in their shape and size, secretion of granules and consequent expression of granule markers (CD62P and CD63), activation of the GPIIb/IIIa integrin complex, exposure of phosphatidyl serine (PS) , which catalyzes thrombin production. Thrombin activates fibrin which polymerizes to form the clot. 

When activated, platelets also secrete over 200 active substances – growth factors and cytokines – with various, sometimes contradictory functions.[4] Understanding how the secretion of these factors is regulated would allow the regenerative potential of the platelets to be harnessed.


What we are doing about it:

In a collaborative project between three institutions – IFG/KIT, Department of Chest, Heart, and Vascular Surgery, Universitätsklinikum Tübingen, and Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht, Teltow, we are -

Analyzing coagulatory and immune responses in blood exposed to materials under static and dynamic conditions. Unlike previous works on this topic, our approach covers all three systems.

Analyzing of protein conformation and protein film composition on surfaces of clinically relevant materials.

Studying molecular mechanisms of platelet activation at surfaces thus linking 1 and 2 above (changes in protein conformation to platelet activation and other responses). In the long-term, our goal is to harness the regenerative potential of the platelets by controlling their activation at implant surfaces.
In pursuing these studies, we are developing standardized conditions for material biocompatibility testing by relying on experience from three laboratories.[5,6]


[1] Ratner BD (2007) The catastrophe revisited: Blood compatibility in the 21st century. Biomaterials 28: 5144-5147
[2] Gorbet MB, Sefton MV (2004) Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. Biomaterials 25: 5681-5703.
[3] Sivaraman B, Latour RA (2012) The relationship between platelet adhesion on surfaces and the structure versus the amount of adsorbed fibrinogen. Biomaterials 31: 832-839.
[4] Nurden AT (2011) Platelets, inflammation and tissue regeneration. Thromb Haemost 105 Suppl 1: S13-33.
[5] van Oeveren W (2013) Obstacles in Haemocompatibility Testing. Scientifica 2013: 392584
[6] Braune S., Grunze M, Straub A, Jung F Biointerphases 2013, 8:33