Injection Of Nanofiber “Peanuts” For Hemostasis

Noncompressible torso hemorrhage (NCTH) is a significant cause of mortality in both civilian and military settings. NCTH is a high-grade injury present in the pulmonary, solid abdominal organ, major vascular, or pelvic trauma domains, or a combination. Rapid operative management, as part of a damage control resuscitation strategy, remains the mainstay of treatment of NCTH.

Of the 1.8 million patients in the 2007-2009 National Trauma Data Bank, 249,505 met the anatomic criteria for noncompressible torso injury. Of these patients, 20,414 (8.2%) had associated hemorrhage, with a 45% mortality rate. Many of these deaths would have been preventable if the victim could have survived the transport phase to a surgical facility. NCTH is also the leading cause of potentially preventable trauma mortality in the battlefield. About half of battlefield deaths in modern warfare are secondary to uncontrolled hemorrhage, which typically involves the torso and/or limb junctional zones. Nearly 1 in 4 fatal battlefield injuries, however, are potentially survivable; 90% of these potentially survivable injuries involve uncontrolled truncal or junctional hemorrhage.

In order to improve the outcomes from these potentially survivable injuries with NCTH, intervention to prevent exsanguination from truncal hemorrhage, which is difficult to compress manually, must be applied in the prehospital setting, prior to the casualty reaching a surgeon. In the current environment, most battlefield-injured patients will survive if they reach a field hospital/forward surgical unit. Unfortunately, in modern warfare, the time required for extrication of a wounded warfighter from the battlefield with transport to a hospital can extend to 6 h or longer. Under these conditions, effective therapies are needed to stabilize patients with NCTH long enough to get them to the hospital alive; implementation of such therapies should improve outcomes from potentially survivable traumatic injury.

Republished with permission from Elsevier from: https://doi.org/10.1016/j.biomaterials.2018.06.031

Current field treatment for NCIAH includes fluid and blood product resuscitation and rapid evacuation to a forward surgical facility. Development of novel treatments for NCIAH in a pre-hospital setting remains a great challenge. The only published device intended for the direct treatment of NCIAH is an expansile polyurethane foam, which still is under development. This foam is not biocompatible (e.g., it requires removal), and also generates dangerously high intraabdominal pressures (~100 mm Hg) during injection, with the potential for pressure injury. Recently, an aortic occlusion catheter (REBOA) was introduced for NCTH, but the general deployment of this device for field stabilization of severe hemorrhage will not be possible in the near future. So currently, there is no available field treatment for NCIAH.

Previous studies have proposed the use of electrospun nanofibers in hemostatic applications. However, traditional electrospinning typically produces uncontrolled and densely packed fibers, resulting in compact two-dimensional (2D) nanofiber mats/membranes which are limited in their applications. Due to limitations imposed by this 2D structure, most previous studies utilizing electrospun nanofibers for hemostatic applications focused on utilizing a bandage without incorporation of hemostatic agents for the treatment of compressible hemorrhage (i.e., bleeding which can be controlled by manual/physical compression, in contradistinction to noncompressible hemorrhage).

In a collaborative study, Xie et al. aimed to develop a treatment for NCIAH, consisting of injectable, superelastic, resorbable, and shape re-expandable nanofiber peanuts supplemented with human clotting factors. The therapy was intended for administration in the prehospital setting, in order to stabilize patients with potentially survivable NCIAH.

In order to do this, an injectable and superelastic nanofiber rectangle matrix (“peanut”) was fabricated by a combination of electrospinning, gas foaming, hydrogel coating and crosslinking techniques. The compressed nanofiber peanut is capable of re-expanding to its original shape in atmosphere, water, and blood within 10 s, exhibiting a greater capacity of water/blood absorption compared to current commercial products and high efficacy in whole blood clotting assay, in particular for thrombin-immobilized samples. These nanofiber peanuts can be packed into a syringe for injection. Further in vivo tests measured the effectiveness of nanofiber peanuts for hemostasis in a porcine liver injury model. This new class of nanofiber-based materials may hold great promise for the treatment of NCIAH.

These findings are described in the article entitled Fabrication of injectable and superelastic nanofiber rectangle matrices (“peanuts”) and their potential applications in hemostasis, recently published in the journal Biomaterials.¹ This work was mainly conducted by Shixuan Chen, Mark A. Carlson, and Jingwei Xie from the University of Nebraska Medical Center, Yu Shrike Zhang from Harvard Medical School, and Yong Hu from Nanjing University.

References:

1. Chen S, Carlson MA, Zhang YS, Hu Y, Xie J. Fabrication of injectable and superelastic nanofiber rectangle matrices (“peanuts”) and their potential applications in hemostasis. Biomaterials 2018, 179, 46-59.