Nonvasoconstrictive Hemoglobin Particles as Oxygen Carriers

Abstract

Artificial oxygen carriers, favorably hemoglobin-based oxygen carriers (HBOCs), are being investigated intensively during the last 30 years with the aim to develop a universal blood substitute. However, serious side effects mainly caused by vasoconstriction triggered by nitric oxide (NO) scavenging due to penetration of nanosized HBOCs through the endothelial gaps of the capillary walls and/or oxygen oversupply in the precapillary arterioles due to their low oxygen affinity led to failure of clinical trials and FDA disapproval. To avoid these effects, HBOCs with a size between 100 and 1000 nm and high oxygen affinity are needed. Here we present for the first time unique hemoglobin particles (HbPs) of around 700 nm with high oxygen affinity and low immunogenicity using a novel, highly effective, and simple technique. The fabrication procedure provides particles with a narrow size distribution and nearly uniform morphology. The content of hemoglobin (Hb) in the particles corresponded to 80% of the Hb content in native erythrocytes. Furthermore, we demonstrate a successful perfusion of isolated mouse glomeruli with concentrated HbP suspensions in vitro. A normal, nonvasoconstrictive behavior of the afferent arterioles is observed, suggesting no oxygen oversupply and limited NO scavenging by these particles, making them a highly promising blood substitute.

Oxygen delivering biomaterials for tissue engineering

“…Xiong et al also fabricated cross-linked hemoglobin and albumin particles with a 700 µm diameter to prevent migration through the endothelium. 36 When they perfused isolated mice glomeruli with these microparticles in vitro , no significant vasoconstriction occurred throughout an 11 min interval. However, further studies are needed to confirm that these hemoglobin-based particles do not cause vasoconstriction in vivo .…”

“…Incorporation of fluorinated zeolite particles in porous, synthetic TE scaffolds for various applications 36 …”

Bio‐inspired nanomedicine strategies for artificial blood components

“…Analogous Hb microparticles carrying about 80% Hb content compared to natural RBCs, have been recently reported where Hb and MnCO 3 were co-precipitated, immediately followed by human serum albumin addition for encapsulation and stabilization of the particles. 109 These particles have shown limited NO scavenging and reduced effect on vasoconstriction. Recent reports have also demonstrated the capability of covalently conjugating Hb directly to the hydrophobic or hydrophilic domain of block-copolymers and then micellize the resultant conjugates to form Hb-loaded micelles.…”

Colloidal micro- and nano-particles as templates for polyelectrolyte multilayer capsules

“…For example, insulin [80] or hemoglobin can be directly loaded into particles by calcium carbonate [81,82] or manganese carbonate templating [83]. Such particles could also be suitable for biocompatible polymer coverage using the layer-by-layer (LbL) assembly approach.…”