Host Reactions To Biomaterials And Their Evaluation

Type I

Type I

Contents released [histamine, etc.]

Type II:

Contents released [htstam ine, etc.]

Type ill:

Time (Days or Weeks)

FIG. 3. Types of hypersensitivity reactions.

Time (Days or Weeks)

FIG. 3. Types of hypersensitivity reactions.

body are present in the circulation at the same time, forming immune complexes that can lodge in the walls of blood vessels. These reactions are unlikely for biomaterials applications except for slowly releasing drug delivery and biodégradation systems.

Type IV hypersensitivity reactions do not involve the production of antibody, but rather involve the production of T cells that react with an antigen. This involves a complex interaction of T cells, macrophages, and soluble mediators. The common manifestation of type IV hypersensitivity is contact dermatitis, which is readily apparent as a skin rash that occurs 24—48 hr after local antigen contact, but systemic reactions are also possible. Type IV hypersensitivity occurs with plants such as poison ivy, industrial chemicals such as metal salts and photo-chemicals, and metal objects such as jewelry and buttons. Contact dermatitis or oral lesions have been seen with the use of metallic biomaterials and acrylics. Deep tissue reactions of type IV hypersensitivity have been reported with the use of various biomaterials, including metals, silicones, and acrylics.


Systemic reactions to biomaterials that degrade or wear are possible. Toxic substances released from a biomaterial may damage a target organ. This can usually be tested for in pretrial screening of the biomaterial by analysis of the chemicals released and by tissue culture analysis of the material, leachables, and degradation and wear products. The biological response to wear products is important and controversial. Many biomaterials are composed of several components and the contribu-

Type IV:

Lymphognes some cause damage

Clonal Expansions FIG. 3—continued tion of the wear products often cannot be attributed to only one component, such as in total joint replacements where the particles from wear can be metallic, polymeric (polyethylene and/or polymethylmethacrylate), and ceramic. Moreover, the relative contributions of particle shape, size, and chemistry are uncertain.

Systemic reactions that are a result of the immune response to the components of the biomaterial are harder to predict, difficult to test for, and need to be evaluated carefully in clinical trials. Since testing prior to release of a biomaterial for general use is extensive, there are relatively few reported clinical reactions of systemic toxicity, immune or nonimmune mediated, to biomaterials applications.

Reactions believed to be caused by hypersensitivity to biomaterials have been most thoroughly studied with metallic devices. Type IV reactions are the most common, but type I or II reactions have also been reported. Immune responses to collagen are of concern since these materials, especially when they are of non human origin, can be potent antigens. Reactions to silicone, as stated before, are controversial; type I, II, and IV responses are possible but difficult to document. Drug delivery systems or other degradative systems that slowly and continually release potentially antigenic substances into the body provide a model for the production of type III responses.


Benjamini, E., and Leskowitz, S. (1991). Immunology, A Short Course.

Wiley—Liss, New York. Cotran, R., Kumar, F., and Robbins, S. L. (1989). Pathologic Basis of Disease. Saunders, Philadelphia. Guyton, A. C. (1991). Textbook of Medical Physiology, 8th Ed. Saunders, Philadelphia. Halliwell, B., et al., eds. (1988). Oxygen Radicals and Tissue Injury.

Fed. Am. Soc. Exp. Biol., Bethesda, MD. Merritt, K. (1986). Immunologic resting of biomaterials. in Techniques of Biocompatibility Testing, (D. F. Williams, ed., Vol. II. CRC Press, Boca Raton, FL. Roitt, I., Brostoff, J., and Male, D. (1989). Essential Immunology.

Blackwell Sci., Boston. Rose, N. R., and Friedman, H. (1980). Manual of Clinical Immunology.' Am. Soc. Microbiol., Washington, DC.

4.5 Blood Coagulation and Blood-Materials Interactions

Stephen R. Hanson and Laurence A. Harker

The hemostatic mechanism is designed to arrest bleeding from injured blood vessels. The same process may produce adverse consequences when artificial surfaces are placed in contact with blood, and involves a complex set of interdependent reactions between (1) the surface, (2) platelets, and (3) coagulation proteins, resulting in the formation of a clot or thrombus which may subsequently undergo removal by (4) fibrinolysis. The process is localized at the surface by complicated activation and inhibition systems so that the fluidity of blood in the circulation is maintained. In this chapter, a brief overview of the hemostatic mechanism is presented. Although a great deal is known about blood responses to injured arteries and blood-contacting devices, important interrelationships are not fully defined in many instances. A more detailed discussion is given in recent reviews (Coleman et al., 1994; Forbes and Courtney, 1987; Thompson and Harker, 1983).

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