Nanomedicine, Volume IIA: Biocompatibility

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

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

Nanorobots, whether passive or active, may become trapped in the microvasculature if any one of their physical dimensions nearly equals or exceeds the diameter of the smallest capillaries, about 4-7 microns (Sections and 15.4.2), thus producing a simple geometric obstruction. Positionally stable nanodevice protrusions (Section into the bloodstream – such as dedicated energy organs (Section 6.4.4) – must be carefully designed to avoid both geometric and overgrowth-related vascular obstruction.

Motile medical nanorobots that are present intravascularly in large concentrations must take care to avoid swimming into “traffic jams” and the formation of a localized embolus (Chapter 12) that could physically block free circulation through a particular vessel [3879]. For example, catheter emboli [3880] are foreign bodies that must be removed from the vasculature [3880]. Similarly, nanocrit concentrations of passive nanorobots higher than 10% may lead to increased viscosity and plug flow of the blood (Sections and and a significant impairment of the systemic circulation. In contrast, the deformability of normal red cells allows them to be packed by centrifugation to nearly 100% cells (vs. only ~60% for hardened red cells [3881]). Leukocytes are much less deformable than erythrocytes, and even more so when neutrophils are activated and are aggregating during phagocytosis of locally dense concentrations of bacteria [3882]. White cells present in large numbers can cause leukostasis [3883-3887]. Leukostasis is a plugging of the microcirculation, especially after mechanical interventions producing surgical trauma [3888, 3889] or unintentional chaotic activation of the complement system [3890].

Vascular spaces may also become physically obstructed by new endothelium that accumulates on almost any surface placed in the circulation for a period of time. In 1963, Stump et al [3891] first observed that a 4.5 cm Dacron vascular implant was fully endothelialized after 7 days of implantation in a pig, and subsequently that a small square Dacron hub suspended in the center of a Dacron prosthesis and having no direct contact with the prosthetic wall became completely coated with endothelial cells after a 4-week canine implantation. Spontaneous endothelialization from the circulating blood has since been confirmed by others [3892-3896]. Unless specifically designed to avoid it, blood-contacting surfaces of large positionally-stable nanorobotic protrusions or aggregates may eventually become coated with endothelial cells. Such cells will have migrated either from the endothelium of adjacent arteries or from nearby capillaries, or will have arrived as bloodborne CD34+ endothelial precursor stem cells which can seed the nanorobotic surface and then differentiate into EC [3896]. Energy organs that emit electrical fields or directly release glucose into the bloodstream may attract both microbes and phagocytes to the site, as well as promoting “benign” neoplastic growth and endothelialization, further increasing the potential for vascular obstruction.


Last updated on 30 April 2004