Title: Nanotechnology via the control of bioprocesses with nanostructured inorganics.
Abstract: This talk will give an overview of our efforts to develop simple, low-cost inorganic remedial agents, for point-of-care therapeutic treatment and control of the external arterial and the internal bleeding that results from traumatic injuries. The nanostructured inorganic material agents were considered as systems, defined by their physical properties, including surface charge, pH-dependent isoelectric point in simulated body fluid (SBF), heat of reaction in SBF, electrolyte delivery, surface area, porosity, nanoparticle morphology and size, and acid-base properties. The goal has been to determine how these properties might be selectively used to control external and internal bleeding as it is defined by the blood-clotting system. The blood-clotting biosystem is self-regulating using clotting as well as anti-clotting to localize the clotting activity, and the therapeutic agent must be consonant with that regulation. The experimental procedures that were used began by in vitro testing of blood coagulation for a variety of property-defined nanostructured inorganic material systems as determined by in vitro thromboelastograph measurements using whole and factor-deficient blood plasma. The research was sponsored by invitation from medical scientists of the United States Office of Naval Research (ONR) during the early stages of the Iraq war. Shelf life, stability, and usability in extreme environments were key requirements along with the figure of merit of stopping major external arterial bleeding in a few minutes of its initiation. The experimental in vitro results obtained at UCSB were validated by ONR researchers, and, when promising, for external arterial bleeding by in vivo hemostasis testing with large animals by the ONR medical center. If that result was a statistical improvement over the best currently used in practice, the agent was commercially packaged and sent to Iraq for “clinical” trial, the results of which were shared with our lab and were used to improve the performance of the inorganic agent for the hemostasis of major arterial bleeding. The best agent was approved by the FDA for civilian use in the United States in 2012, is currently (2019) the preferred agent for external arterial bleeding hemostasis for all branches of the US uniformed services, and is widely used by civilian first responders. The targeting and therapeutic treatment of internal bleeding must address a longer time scale and be inclusive of venous, capillary, and arterial bleeding. A strategy for doing this was developed in a co-PI project by James Morrisey (U. Michigan) and UCSB. The targeting is done using short-chain polyphosphate functionalized silica nanoparticles, which can be safely administered via the cardiovascular network of the body, without inducing coagulation in normal blood. The nanoparticle target is the common pathway of the blood-clotting cascade system, which is normally activated at a bleeding site by short-chain polyphosphate oligomers that are released by blood platelets at the trauma site.