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Biomaterials Tutorial

Protein Adsorption  

Elizabeth Leber
University of Washington Engineered Biomaterials

When biomaterials are implanted into animals or humans, protein adsorption onto the foreign surface occurs within seconds of implantation [1-8].  This rapid protein adsorption means that cells arriving at the biomaterial surface probably interact with the adsorbed protein layer rather than directly with the material itself [1 2, 6-8].  Thus, the initial protein adsorption onto a biomaterial surface plays a key role in how the body responds to an implanted biomaterial. The body’s first response to any injury is inflammation, and much study has been done on the influence of protein adsorption on the inflammatory response.  The primary plasma proteins are albumin, immunoglobulins, and fibrinogen,  while Hageman factor, high molecular weight kinogen (HWMK), and factor VIII/vWF are present in lesser but possibly significant numbers and also compose the adsorbed protein layer [9].  Here we will briefly describe the role of the three primary plasma proteins in the body’s initial inflammatory response to injury. 


Albumin is the predominant plasma protein, making up 60-70% of plasma [4], yet it is not considered a mediator of acute inflammation.  Although there is evidence that monocytes can and do, at least in vitro, adhere to albumin-coated surfaces, albumin is generally considered to “passivate” the surface and greatly reduce the acute inflammatory response to the material [1, 4, 7, 10].  Other constituents of plasma, despite their smaller numbers, must influence the adherence of phagocytic cells involved with inflammation [4]. 


Immunoglobulins comprise about 20% of the plasma, making them the second most abundant class of plasma proteins [4]. Yet, they also do not appear necessary for initiation of the inflammatory response.  Although experiments have shown that large concentrations of immunoglobulin G (IgG) adsorb onto multiple biomaterial surfaces in vitro[11] and similar results have been observed following brief periods of implantation [4], IgG adsorption does not appear necessary for induction of the inflammatory response to biomaterial implants.  This finding is based on implantation of PET (polyethylene terephthalate) disks in severe combined immunodeficient (SCID) mice that have extremely low plasma IgG levels.  After a 16-hour implantation, the implants had no detectable surface IgG, but the number of adherent phagocytic cells was not substantially decreased from the number adhered to disks implanted in normal mice [1, 4, 7]. 


Fibrinogen is the third primary plasma component.  In contrast to albumin and IgG, however, fibrinogen appears to play a major role in the inflammatory response.  It immediately adsorbs to implanted biomaterials and experiments suggest that it undergoes denaturation following adsorption.  This transformation following adsorption onto a surface [8] leads to the fibrinogen adhering more strongly to the material.  The degree of fibrinogen denaturation on a material surface correlates strongly with the degree of acute inflammatory response [6, 12].  Additionally, implantation into mice which lack circulating fibrinogen shows a lack of an inflammatory response to the implanted material unless the material has been pre-coated with fibrinogen or plasma [1, 13, 14].  Thus, fibrinogen is a necessary component of inflammatory cell recruitment to implanted biomaterials. 


1.         Tang L, Eaton JW. Inflammatory responses to biomaterials. Am J Clin Pathol 1995; 103(4): 466-71.

2.         Bohnert JL, Horbett TA. Changes in adsorbed fibrinogen and albumin interactions with polymers indicated by decreases in detergent elutability. Journal of Colloid and Interface Science 1986; 111:363-377.

3.         Bohnert JL et al. Plasma gas discharge deposited fluorocarbon polymers exhibit reduced elutability of adsorbed albumin and fibrinogen. J Biomater Sci Polym Ed 1990; 1(4):  279-97.

4.         Tang L, Lucas AH, Eaton JW. Inflammatory responses to implanted polymeric biomaterials: Role of surface-adsorbed immunoglobulin G. J Lab Clin Med 1993; 122(3): 292-300.

5.         Gristina AG. Implant failure and the immuno-incompetent fibro-inflammatory zone. Clin Orthop 1994; 298: 106-18.

6.         Tang L et al. Anti-inflammatory properties of triblock siloxane copolymer-blended materials. Biomaterials 1999; 20(15): 1365-70.

7.         Tang L, Eaton JW. Natural responses to unnatural materials: A molecular mechanism for foreign body reactions. Mol Med 1999; 5(6): 351-8.

8.         Balasubramanian V. et al. Residence-time dependent changes in fibrinogen adsorbed to polymeric biomaterials. J Biomed Mater Res 1999; 44(3): 253-60.

9.         Anderson, JM, Bonfield TL, Ziats NP. Protein adsorption and cellular adhesion and activation on biomedical polymers. Int J Artif Organs 1990; 13(6): 375-82.

10.       Tang L et al. Molecular determinants of acute inflammatory responses to biomaterials. J Clin Invest 1996; 97(5): 1329-34.

11.       Pankowsky DA et al. Morphologic characteristics of adsorbed human plasma proteins on vascular grafts and biomaterials. J Vasc Surg 1990; 11(4): 599-606.

12.       Tang L, Wu Y, Timmons RB. Fibrinogen adsorption and host tissue responses to plasma functionalized surfaces. J Biomed Mater Res 1998; 42(1): 156-63.

13.       Tang L, Eaton JW. Fibrin(ogen) mediates acute inflammatory responses to biomaterials. J Exp Med 1993; 178(6): 2147-56.

14.       Szaba FM, Smiley ST. Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood 2002; 99(3): 1053-9.