Biomaterials interactions with blood

Tan, J.S. Butterfield, D.E. Voycheck, C.L. Caldwell, K.D. Li, J.T. Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats. Biomaterials 1993,14, 823-833. 

In the following, we will focus on in vitro tests for cell compatibility and blood compatibility. In this context, we will also discuss ISO 10993-5 (tests for in vitro cytotoxicity) and ISO 10993-4 (selection of tests for interactions with blood). Finally, the risk of pyrogens in the biomaterial context, especially of bacterial toxins (endotoxins), will be briefly highhghted and selected methods for determining pyrogens/endotoxins (cf. also ISO 10993-11) will be presented. 

This is an edited volume containing 23 chapters. Three chapters deal with biomaterials in general, 6 chapters address specific blood and tissue interactions with biomaterials, 10 chapters address the use of biomaterials in specific surgical disciplines, and 3 chapters address tissue engineering and genetic manipulation of cells. The reference list for each chapter is extensive. This is an excellent overview of how biomaterials interact with the host and the specific use of biomaterials in indicated applications. 

From a clinical point of view, a biomaterial can be considered as blood compatible when its interaction with blood does not provoke either any damage of blood cells or any change in the structure of plasma proteins. Only in this case can it be concluded that this material fulfills the main requests of biocompatibility [9]. As a consequence of the non-specific protein adsorption and adhesion of blood cells, the contact of any biomaterial with blood often leads to different degrees of clot formation [22-24]. 

Ito, Y, Miyashita, K., Kashiwagi, T., and Imanishi, Y. (1993) Synthesis and interactions with blood of polyether-urethaneurea/polypeptide block copolymers. Biomaterials Artificial Cells and Immobilization Biotechnology, 21,571-580. 

Ikada, Y., Suzuki, M., Tamada, Y. Polymer surfaces possessing minimal interaction with blood components. In Polymers as biomaterials, pp 135-147. Springer, Heidelberg (1984)... 

Another field of application of fluorinated biomaterials is connected to lesions or evolving disease pathology of blood vessels. In particular, arteries may become unable to insure an adequate transport of the blood to organs and tissues. Polytetrafluoroethylene (PTFE) and expanded e-PTFE are the preferred materials for vascular prostheses. The interactions of blood cells and blood plasma macromolecules with both natural and artificial vessel walls are discussed in terms of the mechanical properties of the vascular conduit, the morphology, and the physical and chemical characteristics of the blood contacting surface. 

Labarre, D., Vauthier, C., Chauvierre, C., Petri, B., Muller, R., and Chehimi, M. M. (2005), Interactions of blood proteins with poly(isobutylcyanoacrylate) nanoparticles decorated with a polysaccharidic brush, Biomaterials, 26(24), 5075-5084. 

A study has been carried out on the interactions of blood with plasticised poly(vinyl chloride) biomaterials in a tubular form. The influence of different factors such as the biomaterial, antithrombotic agent, blood condition and the nature of the application is represented when considering the blood response in the clinical utilisation of the plasticised PVC. The PVC was plasticised with di-(2-ethylhexyl)phthalate (DEHP) and tri-(2-ethylhexyl)trimellitate (TEHTM)and in-vitro and ex-vivo procedures used to study the biomaterial with respect to the selection of the plasticiser. The blood response was measured in terms of the measurement of fibrinogen adsorption capacity, thrombin-antithrombin III complex and the complement component C3a. X-ray photoelectron spectroscopy was used for surface characterisation of the polymers and the data obtained indicated that in comparison with DEHP-PVC, there is a higher reactivity... 

The blood-materials interactions section contains a review article dealing with surface characterization. Consideration of the surface structure of biomaterials is critical to every study in this volume. This section contains 16 chapters dealing with the choice of in vivo and in vitro methods of biomaterials evaluation, biomaterials selection and modification, and cellular interactions with candidate surfaces. Individual papers dealing with the use of dogs, baboons, and goats for in vivo blood-materials evaluation can be found together with in vitro methods. There are also several contributions on polyurethanes, which are prime candidates for use in blood contacting devices. 

Methodologies to evaluate the interaction of biomaterials with blood and blood components vary from in vitro systems, where anticoagulated blood or blood fractions are contacted with surfaces in a variety of configurations, to in vivo procedures, where tubes, sheets, etc. are inserted into the vascular system. A compendium of these techniques that seek to understand the complex interactions of blood with surfaces recently was assembled (1). 

The Canine Model. While ex vivo models often are considered to be an improvement over in vitro biocompatibility test systems, the problem of describing extremely complex blood—polymer interactions still remains. In this study, we used radioisotope-labeled proteins and platelets and scanning electron microscopy. In other studies, we applied immunolabeling techniques and transmission electron microscopy. The application of these tools to an in vivo or ex vivo system provides more pertinent data than that often obtained in an in vitro system. Through this approach we hope to gain some insights into the complicated interactions of blood with biomaterials. 

Selection of biomaterials for circulatory assist devices is a task made difficult by the complexity of the interfacial interactions between blood and the solid surfaces of candidate materials. Among the major factors contributing to the complexity are surface charge, surface energy, surface roughness, chemical reactivity, adsorptivity, hydrophobicity, etc. To further aggravate the complexity, the factors noted interact with each other in ways that are not as yet understood or well-defined. 

FTIR spectroscopy has proven to be particularly useful in gaining an understanding of the biocompatibility phenomenon. It is believed [746, 841, 856, 857] that protein adsorption is the initial step in the interaction of blood with implanted biomaterials, followed by adhesion of cells and subsequent tissue attachment. This implies that the substrate surface characteristics influence the process, which was confirmed by ATR studies of albumin adsorption on calcium phosphate bioceramics and titanium [763] and segmented polyurethane [764], albumin and fibrinogen on acetylated and unmodified cellulose [765, 766], poly(acrylic acid)-mucin bioadhesion [767], polyurethane-blood contact surfaces [768], and other proteins on poly(ester)urethane [769], polystyrene [767, 771] and poly(octadecyl methacrylate) [771] and by IRRAS study of adsorption of proteins on Cu [858]. Another branch of IR spectroscopic studies of protein adsorption relates to microbial adhesion (Section 7.8.3). 

The cardiovascular system consists of the heart and all the blood vessels. Cardiovascular biomaterials may contact blood (both arterial and venous), vascular endothelial cells, fibroblasts, and myocardium, as well as a number of other cells and acellular matrix material that make up all biological tissue. This chapter will consider a wide range of biomaterials that interact with the heart, blood, and blood vessels. 

Numerous controversial theories on blood-compatible polymers have been reported, because the interactions of blood with polymer surfaces leading to thrombus formation are governed by many chemical, physical, and biological parameters and difficult to analyse in detail. The important variables affecting thrombus formation on biomaterials include chemical composition of the surface, physical texture of the surface, disturbance of blood flow induced by the polymer, the kind of animals used, the physical conditions and local place of the tested body, etc. Furthermore, the evaluation methods employed for blood compatibility are important because different evaluation methods lead to different conclusions therefore, a standard sample is strongly desired At least, in the final test stage it is essoitial to evaluate the blood compatibility under conditions applied in practice. 

Polytetrafluoroethylene, polyurethanes, polyethylene, silicones and acrylates have been proposed for replacement of both hard and soft tissues. These biomaterials must satisfy two in5)ortant criteria to provide an useful function in a biological environment they should possess the proper physical characteristics as replacement materials and should exhibit compatible interfacial properties with surroimding tissues and fluids. The interaction of blood with foreign surfaces resulting in thrombogenesis has received considerable attention, but still represents a problem. 

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