Application of SEAL for Internal Hemorrhage Control

Introduction

Uncontrolled internal bleeding following trauma is a leading cause of combat mortality, as warfighters can rapidly lose large blood volumes. A particular threat is non-compressible torso hemorrhage in the thoracic, abdominal, or pelvic regions, where deep vascular injuries defy control by direct external pressure or tourniquets due to anatomical depth.

Management of internal bleeding remains a substantial and growing unmet clinical need. In deep, non-compressible, or surgically inaccessible injury sites, targeted hemostatic agents are essential to accelerate clot formation, stabilize fragile clots, and achieve timely hemorrhage control, ultimately improving survival and enabling definitive surgical repair.

Few hemostatic agents have received FDA 510(k) clearance for internal hemorrhage, limited to non-absorbable hemostatic gauze (removal within 2 days) or non-absorbable hemostatic sponge (removal within 4 hours). However, these non-absorbable agents pose unique challenges for internal use, as surgical removal introduces significant procedural risks and complications.

Advantages of SEAL

The biopolymer chitosan appears ideal for treating internal traumatic wounds, as it is bioabsorbable, nontoxic, and offers strong hemostatic and antimicrobial properties. SEAL incorporates a specifically activated form of chitosan to create a highly potent hemostatic material.

The design of SEAL is advantageous in austere environments. SEAL is easily identifiable, durable in field conditions, and lightweight, making it easy to pull from the injured person’s individual first aid kit or a corpsman medic bag that might contain several. The spray design reduces application time and enables use in the darkness, wind, and rain without losing efficacy. In addition, it allows treating deep, hard-to-access wounds that typical product designs, such as gauze, can not reach.

Testing of SEAL in Models of Internal Hemorrhage Control

BC3 has conducted substantial pre-clinical research regarding the efficacy and safety of SEAL for internal hemorrhage control. This included:

1. Systematic testing in the rat liver resection model

2. Pilot testing to control parenchymal hemorrhage in normal and coagulopathic swine

1) Efficacy and Safety Testing in Rat Internal Hemorrhage Model

Systematic studies in the rat liver resection model confirmed the high efficacy and safety of SEAL in the management of internal hemorrhage. In an initial set of experiments, the efficacy of SEAL was tested against Celox and untreated controls in both non-heparinized animals and those given high-dose heparin to simulate severe coagulopathy. All non-heparinized animals survived the surgery, whereas all heparinized animals in the Celox and control groups died. Two SEAL-treated animals survived the surgery for more than one hour, and one survived overnight. The SEAL group showed reduced blood loss and bleeding time compared to Celox and control animals (Figure 1).

Figure 1: Efficacy of SEAL to stop severe internal bleeding in normal and coagulopathic (heparinized) animals (n=3).

A subsequent rat liver resection study examined coagulopathic animals after low-dose heparin treatment to increase survival rates and assess key health and biosafety parameters, including histological analysis on days 1 and 7 post-surgery. All animals in the SEAL group survived surgery, whereas two animals from the Celox group and three control animals died within the first day. The SEAL group showed the lowest blood loss. Blood parameters remained normal and comparable across groups. As a result of increased inflammatory reaction, the Celox group showed significantly greater body weight loss and tissue adhesions than the SEAL group (Figure 2).

Figure 2: Body weight loss and intra-abdominal adhesions in heparinized animals (n=6).

2) Efficacy Testing in Swine Parenchymal Bleeding Model

In preliminary experiments conducted by Dr. Bijan Kheirabadi (USAISR), SEAL’s efficacy in controlling parenchymal hemorrhage was evaluated in normal and coagulopathic swine. Results showed that SEAL effectively controlled bleeding in a severe Grade III/IV liver injury model. Inspection of the peritoneal cavity at one hour revealed stable hemostasis. Removal of gauze packs at one hour did not cause rebleeding, and hemostasis remained secure during the second hour of monitoring.

Dr. Kheirabadi concluded that these results were highly encouraging: despite the severe liver injury, SEAL stopped the bleeding and maintained hemostasis throughout the study.