Nanofibrous Snake Venom Hemostat

Abstract

Controlling perioperative bleeding is of critical importance to minimize hemorrhaging and fatality. Patients on anticoagulant therapy such as heparin have diminished clotting potential and are at risk for hemorrhaging. Here we describe a self-assembling nanofibrous peptide hydrogel (termed SLac) that on its own can act as a physical barrier to blood loss. SLac was loaded with snake-venom derived Batroxobin (50 μg/mL) yielding a drug-loaded hydrogel (SB50). SB50 was potentiated to enhance clotting even in the presence of heparin. In vitro evaluation of fibrin and whole blood clotting helped identify appropriate concentrations for hemostasis in vivo. Batroxobin-loaded hydrogels rapidly (within 20s) stop bleeding in both normal and heparin-treated rats in a lateral liver incision model. Compared to standard of care, Gelfoam, and investigational hemostats such as Puramatrix, only SB50 showed rapid liver incision hemostasis post surgical application. This snake venom-loaded peptide hydrogel can be applied via syringe and conforms to the wound site resulting in hemostasis. This demonstrates a facile method for surgical hemostasis even in the presence of anticoagulant therapies.

Active nano/microbilayer hemostatic agents for diabetic rat bleeding model

“…18 For example, Kumar et al reported that snake venom laded self-assembling nanofibrous peptide hydrogel is a facile method for surgical hemostasis. 19 Similarly, Hsu et al showed that self-assembling peptides, especially RADA16-I, are highly effective in generating in hemostasis with a hemostasis time of <10 s. 20 In their study, an antibiotic released self-assembled film developed for rapid hemostat. 21 Recently, self-assembling peptide scaffolds have been under extensive investigations for effective hemorrhage control.…”

“…These materials have several problems, such as batch‐to‐batch variability and carry risk of biological contamination, because of xeno‐/allogenic characteristics . For example, Kumar et al reported that snake venom laded self‐assembling nanofibrous peptide hydrogel is a facile method for surgical hemostasis . Similarly, Hsu et al showed that self‐assembling peptides, especially RADA16‐I, are highly effective in generating in hemostasis with a hemostasis time of <10 s .…”

Recent Advances in Hemostasis at the Nanoscale

“…Uncontrolled traumatic and surgical bleeding are leading causes of fatality (casualties) in warfare, accidents, disaster, and crime . Excessive bleeding disrupts hemodynamics, requires transfusions, prolongs operative time, and adds a huge burden on healthcare system . Hemorrhage accounts for about 35% of trauma mortality, and 40% of these deaths happens before admission to the hospital .…”

“…In cases of severe or uncontrolled blood loss, the body's natural clotting process is not able to facilitate hemostasis on its own, which calls for external hemostasis. The critical design requirements for the hemostats are to 1) provide a localized physical barrier to entrap red blood cells (RBC), 2) provide a chemical platform that accelerates clotting regardless of the presence of heparin, 3) stop bleeding in a rapid fashion (<1 min), and 4) prevent hemorrhaging during subsequent manipulation …”

Multifunctional Shape‐Memory Polymer Foams with Bio‐inspired Antimicrobials

“…However, this technology shows promise for use in embolic applications. Another recently developed hydrogel‐based hemostatic material includes an injectable nanofibrous peptide hydrogel that has been loaded with snake‐venom derived Batroxobin . The material promotes clotting by physically blocking blood flow and utilizing a hemostatic drug, even in the presence of heparin, resulting in improved liver incision hemostasis in a rat model in comparison to clinical controls.…”