© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003

15.2 Classical Biocompatibility

The question of biocompatibility [234-237] arises whenever any foreign substance – be it natural materials [6054], therapeutic cells, a transplanted organ, an artificial implant, or a medical nanorobot – is placed inside the human body for medical purposes. The most general definition of biocompatibility is: “the ability of a material to perform with an appropriate host response in a specific application” [230], or, alternatively: “the exploitation by materials of the proteins and cells of the body to meet a specific performance goal” [231], but neither of these really tells the whole story. The term “biocompatibility,” as used in this book, will refer to an assessment of the totality of nanorobot surface material-tissue interactions, both local and systemic. These interactions classically may include [231-234]:

(1) Cellular Adhesion Effects – including (A) weak interactions with a nonadhesive surface, (B) strong nonspecific interactions leading to attachment and de-differentiation* of highly specialized cell types (e.g., leading to the attachment of monocytes, conversion to macrophages, the formation of giant cells, the recruitment of fibroblasts, and, at later stages, fibrosis), (C) strong specific interactions with surfaces containing appropriate receptor sites arrayed at the appropriate density (e.g., cells attach, do not de-differentiate,* and perform highly specific functions), and (D) encasement in a gel or matrix either containing active receptor sites or a matrix that is noninteracting, wherein the 3D cell-matrix contact permits the cell to function in a physiologically normal manner;

(2) Local Biological Effects – such as cell viability and mitotic function (cell proliferation, cell cycle phases), cell metabolic activity (cell protein content), and plasma membrane integrity; blood-material interactions (e.g., blood platelet adhesion and activation, leading to thrombogenesis, complement activation, or hemolysis); toxicity (e.g., the leaching of cytoreactive substances from biomaterials), modification of normal healing (e.g., encapsulation, foreign body reaction and pannus overgrowth), infection, and tumorigenesis;

(3) Systemic and Remote Effects – such as embolization of clots or biomaterial hypersensitivity, elevation of usual components in blood, systemic toxicological response, lymphatic particle transport, systemic distribution and excretion, effects of degradation products on remote organ functions (including interactions of degradation products with therapeutic agents or devices), and allergic, pyrogenic, carcinogenic, and teratogenic responses; and

(4) Effects of the Host on the Implant – such as physical or mechanical effects, stability and biological degradation processes (e.g., absorption of substances from tissues, enzymatic damage, or calcification), immune responses such as inflammation, fibrosis or granuloma formation around the implant, or co-option of implant structure or function.

* De-differentiation is the loss by mature cells of some of their specialized properties and reversion to a less developed state [5484]. De-differentiation is a normal part of healing and regeneration [5485], can be induced mechanically [5486], and is often a part of early tumor development [5487].

Chapter 15.2 opens with a brief summary of the current (2002) status of medical implant biocompatibility (Section 15.2.1), followed by a general discussion of protein interactions with implant surfaces (Section 15.2.2), immunoreactivity (Section 15.2.3), inflammation (Section 15.2.4), coagulation and thrombosis (Section 15.2.5), allergic reactions and shock (Section 15.2.6), fever (Section 15.2.7), and finally mutagenicity and carcinogenicity (Section 15.2.8), especially as applied to medical nanorobots.

Last updated on 30 April 2004