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WIREs Nanomed Nanobiotechnol
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At the nanoscale: nanohemostat, a new class of hemostatic agent

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Abstract Three basic categories of hemostats are widely used in surgery today: chemical agents, thermal devices, and mechanical methods that use pressure or ligature to slow bleeding. Each has its benefits and limitations. However, nanotechnology is rapidly ushering in new medical technologies. This review focuses on the ‘nanohemostat’, a new class of hemostatic agent that stops bleeding in less than 15 seconds by using (RADA)4, referred to as nanohemostat‐1 (NHS‐1), a synthetic biological material that self‐assembles at the nanoscale when applied to a wound, and compares it to the characteristics of the ‘ideal hemostat’. WIREs Nanomed Nanobiotechnol 2011 3 70–78 DOI: 10.1002/wnan.110 This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery

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Hemostasis in a spinal cord injury after 1% nanohemostat‐1 (NHS‐1) was applied to the wound site. After laminectomy and opening of the dura, the spinal cord was hemisected at T2, from the dorsal to ventral aspect and treated with 20 µL of 1% NHS‐1. (a) Hemostasis was achieved in 7.6 seconds. In the saline controls (b) it took on average 163 seconds to stop the bleeding (scale bar = 1 mm).

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Complete hemostasis in brain (adult rat cortex hemostasis). The pictures are time‐lapse images at each stage of the experiment for brain. (a–e) Part of the overlying skull was removed in an adult rat, and one of the veins of the superior sagittal sinus was transected and treated with 1% self‐assembling nanohemostat‐1 (NHS‐1). (f–j) The control with iced saline. (a and f) The brain and veins of the superior sagittal sinus (SSS) are exposed. (b and g) Cutting the vein. (c and h) Bleeding of the ruptured vein. (d) NHS‐1 is applied to the site of injury. (i) Iced saline is applied to the site of injury in the control. (e) All bleeding stopped 20 seconds after application. (h) The control: the surgical field was fully obscured and surgery had to stop until the area was clear of blood (scale bar = 1 mm).

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Self‐assembling peptide nanofiber scaffold. (a) Molecular model of the nanohemostat‐1 (NHS‐1) RADA16‐I (arginine, alanine, aspartate, alanine) molecular building block. (b) Molecular model of numerous RADA16‐I molecules undergoing self‐assembly to form well‐ordered nanofibers with the hydrophobic alanine sandwich inside and hydrophilic residues on the outside. (c) NHS‐1 1% is examined using an atomic force microscopy (scale bar = 5000 nm).

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Rat liver hemostasis (a–h). This series of pictures is of an adult rat where the skin covering the intraperitoneal cavity was opened and the liver exposed in both (a and e). (e–h) Saline controls. (b and f) The left lateral lobe received a sagittal cut completely transecting a portion of the liver lobe. (b) The transection is from the upper left to the lower right. (f) The cut is from the upper right to the lower left. (c) The liver is separated and the two halves are allowed to come back together and the bleeding continues. (g) The liver is bleeding profusely in the upper left and is filling the cavity. (d) The 1% nanohemostat‐1 (NHS‐1) solution was applied and the extent of the incision is visible under the transparent assembled NHS‐1 (arrow). Complete hemostasis was achieved in 8.6 + 1.7 seconds (not shown), which is statistically significant when compared to 90.0 + 5.0 seconds when cauterization was applied (not shown), or 301.6 + 33.2 seconds if irrigated with saline (h). In (h) the cotton swab is being used to slow the bleeding and make the area visible. The cavity is full and is leaking at the bottom of the frame (scale bar = 4 mm).

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Junction of sciatic nerve and femoral artery (rat). (a and f) The exposed sciatic nerve and the femoral artery. (b and g) The femoral artery transection with scissors (lower right). (c and h) Subsequent bleeding. (d) Treatment with nanohemostat‐1 (NHS‐1). (e) The area 5 seconds after application of the NHS‐1. Note that there is complete hemostasis and a clear field. Self‐assembly of the NHS‐1 causes a phase change to a gel, in the presence of blood. The assembled material can be easily suctioned from the site. Complete hemostasis was maintained for the 1‐h test. The control (f–j). In (i), iced saline was applied to the site to slow bleeding. However, bleeding continued for 6 min when pressure was applied and each time the pressure was released the bleeding (j) restarted (scale bar = 1 mm).

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Liver 4‐mm punch biopsy. A 4‐mm core was removed from the left liver lobe and the hole was treated with either nanohemostat‐1 (NHS‐1) (a–d) or saline (e–h). (a and e) The punch and the removal of a 4‐mm core from the left liver lobe and both showed profuse bleeding. (b) The hole was treated with 3% NHS‐1, which brought about complete hemostasis in 9.7 + 1.2 seconds. (c) All bleeding stopped 15 seconds after treatment; also there was no bleeding under the liver. Both (c and g) are 30 seconds after the punch. (f) The control was treated with iced saline and cautery; 10 seconds after punch (g) bleeding continued for 3.5 min and slowed just before closure. Both groups were allowed to survive for 6 weeks. (d) The same NHS‐1 treated liver 6 weeks after punch and treatment (note the small defect; arrow). (h) There is a large growth (arrow) (scale is 4 mm).

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Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery
Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

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