ABSTRACT
T he question of biocompatibility234'237 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 pur poses. The most general definition o f biocompatibility is: “the abil ity o f a material to perform with an appropriate host response in a specific application”,230 or, alternatively: “the exploitation by mate rials of the proteins and cells o f the body to meet a specific perfor mance goal”,231 but neither o f these really tells the whole story. The term “biocompatibility,” as used in this book, will refer to an assess ment of the totality of nanorobot surface material-tissue interac tions, 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 lead ing to attachment and de-differentiation* of highly specialized cell types (e.g., leading to the attachment of monocytes, con version to macrophages, the formation of giant cells, the re cruitment of fibroblasts, and, at later stages, fibrosis), (C) strong specific interactions with surfaces containing appropriate recep tor 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 re ceptor sites or a matrix that is noninteracting, wherein the 3D cell-matrix contact permits the cell to function in a physiologi cally normal manner;
2. Local Biological Effects — such as cell viability and mitotic func tion (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 sub stances from biomaterials), modification of normal healing (e.g., encapsulation, foreign body reaction and pannus overgrowth), infection, and tumorigenesis;
3. Systemic a nd Remote Effects — such as embolization o f clots or biomaterial hypersensitivity, elevation o f usual components in blood, systemic toxicological response, lymphatic particle trans port, system ic distribution and excretion, effects o f degrada tion products on remote organ functions (including interac tions of degradation products with therapeutic agents or de vices), and allergic, pyrogenic, carcinogenic, and teratogenic responses; and
4. Effects o f the H ost on the Im plant — such as physical or mechani cal 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.
