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 Ulcerative Vasculopathy

A macroscale nanorobot aggregate might cause luminal vascular ulceration by prolonged mechanical pressure against intimal tissues, similar to pressure necrosis or epithelial pressure ulcers (Section The symptoms might appear similar to the inflammatory condition of necrotizing vasculitis, whose cause is unknown but is probably usually related to autoimmune factors [5598]. Prolonged pressure could induce apoptosis. For example, mechanical stretch induces apoptosis in mammalian cardiomyocytes [3902] and hypertension caused by hydrostatic edema can induce apoptosis in capillary endothelial cells [3820]. Another example of mechanical ulceration, though not, strictly speaking, within a vascular lumen, is IUD-induced metrorrhagia [3903] (nonmenstrual uterine bleeding), wherein the intrauterine device elicits a vascular reaction that is most pronounced in the endometrium adjacent to the device. This reaction includes increased vascularity and degeneration with defect formation, which may lead to interstitial hemorrhage due to vascular damage from mechanical stress transmitted by the IUD through the endometrium to its vascular network [3903].

Except in unusual cases [3904], indwelling catheters can rest snugly against the vascular walls without complication for long periods of time – common recommendations that indwelling lines should be changed every 2-7 days [5599] are motivated by the ever-increasing risk of bacterial infection over time, not by the risk of vascular ulceration. A biological-like interface would further reduce the chances for nanorobotic-related ulceration in longer-term medical missions involving permanent or semi-permanent implants. In one study, a stented aortic graft was placed endovascularly inside the native aorta of male sheep, and a histological examination 6 months later found good incorporation of the graft with no pressure necrosis, although there was a foreign body reaction around the graft and an organized blood clot was noted between the graft and the aortic wall [3905]. (C. Wiley notes these are now in fairly common use in humans for repairing abdominal aortic aneurysms.) A few possible cases of vascular ulceration are also known – e.g., a chronic indwelling catheter that led to erosion and rupture of the anterior wall of the right ventricle, producing a near-exsanguinating hemorrhage [3933] (far more serious than traditional cardiac tamponade).

Ideally, long-duration nanorobotic organs or nanoaggregates that must maintain close contact with endothelium should employ a mechanically compliant coating having properties similar to extracellular matrix. All such linkages should be not just immunocompatible but also mechanocompatible, possessing an elasticity or mechanical compliance [3906] equivalent to the underlying tissue to which attachment must be secured. Compliance design may include assessments of: (1) circumferential compliance (measurement of changes in vessel diameter over a complete cardiac cycle, including pressure-radius curves [3907], dynamic compliance [3908], and mechanical hysteresis effects) [3906]; (2) longitudinal compliance (elasticity of selected lengths of the vascular system, including any localized stiffening) [3909]; (3) tubular compliance (imparity of elasticity between a prosthetic conduit and the native artery, elastic energy reservoiring, and pulsatile energy losses due to interfacial impedance mismatches) [3910]; and (4) anastomotic compliance (suture line anastomotic compliance mismatch and the para-anastomotic hypercompliance zone [3911, 3912], localized regions of excessive mechanical stress [3913-3915], and cyclic stretch effects on replication of vascular SMC and extracellular matrix [3914, 3917]). A mismatch in mechanical properties between relatively compliant arteries and less-compliant metallic stents [3918] and tissue grafts has been thought to influence patency [3913] and pseudointimal hyperplasia [3914-3916]. Larger more central arteries are more compliant than the distal small-caliber arteries [3919]. Wall shear stress from blood flow differs on either side of a curving vessel and the stress is out of phase with the pulsing circumferential stretch strain [3920]. Significant compliance mismatch between host artery and prosthetic graft may promote subintimal hyperplasia [3911].


Last updated on 30 April 2004