The Terasaki Institute for Biomedical Innovation has created a device that provides rapid hemorrhage management, has minimal inflammatory effects, and provides infection control. Most notably, it has tunable rates of biodegradation, making it usable for both internal and external use, and features sensing capabilities for long-term hemorrhage monitoring.
Newswise — (LOS ANGELES) – June 28, 2023 -The scientists at the Terasaki Institute for Biomedical Innovation (TIBI) have developed a sophisticated device with multiple capabilities to effectively treat deep, non-compressible, and irregularly-shaped wounds. In their recent publication in Advanced Science, they describe a groundbreaking device that addresses rapid hemorrhage management, minimizes inflammatory effects, and ensures infection control. Additionally, the device offers tunable biodegradation rates, allowing for its application both internally and externally. Furthermore, it incorporates sensing capabilities for continuous monitoring of hemorrhage over an extended period. This versatile device is invaluable for timely detection and control of bleeding in surgical wounds, traumatic injuries, and critical illnesses.
Presently, several products are available for hemorrhage control, such as cotton or gauze bandages, powders, and tourniquets. However, these products are primarily designed for shallow and uniformly shaped wounds, relying on compression alone, and lack the ability to simultaneously detect bleeding and control hemorrhage. In contrast, the new device employs highly absorbent shape-memory sponges that effectively treat deep and irregularly shaped wounds while retaining their structure and original dimensions. Following blood absorption, these sponges naturally apply pressure to the wound, facilitating coagulation. While cellulose-based shape-memory sponges are adequate, they lack biodegradability, unlike their gelatin-based counterparts. Moreover, neither type possesses hemorrhage detection capabilities.
The scientists at the Terasaki Institute for Biomedical Innovation (TIBI) utilized silk fibroin, a protein derived from the Bombyx mori silkworm, to develop a versatile device for managing hemorrhage. Silk fibroin possesses desirable properties such as biodegradability, excellent anti-inflammatory effects, and mechanical strength. By engineering this material into porous, highly absorbent memory-shaped sponges, the TIBI team created a novel solution that not only facilitates coagulation and tissue regeneration but also allows for tunable degradation rates. This feature enables long-term use within the body and the potential integration of bleeding monitoring sensors.
Building upon these capabilities, the TIBI team designed an all-in-one hemorrhage management device. This device comprises two layers of silver nanowires positioned above and below a hemostatic sponge layer. The silver nanowires serve dual functions as hemorrhage detection sensors and antibacterial agents.
The researchers conducted a comprehensive evaluation of the device, assessing its mechanical properties, biocompatibility, and biodegradation. The silk fibroin sponges demonstrated exceptional elasticity, absorption capacity, and maintenance of pore size, shape, and structure when tested with water and blood. By adjusting the concentration of silk fibroin, the device's mechanical properties can be tailored to match the surrounding wound tissue, thus optimizing hemorrhage control. Both the sponge and nanowire layers exhibited favorable biocompatibility and minimal inflammatory responses, as evidenced by good cellular viability and proliferation observed in connective tissue samples. Furthermore, by increasing the silk fibroin concentration and incorporating a methanol wash step during fabrication, the degradation rate of the sponge could be slowed down, offering greater control over its biodegradation process.
Subsequently, an assessment was conducted on the device and a commercially available gelatin-based anti-hemorrhage device using rat models through subcutaneous implantation. After a period of four weeks, the commercial sponge completely degraded, whereas the silk fibroin nanowire device maintained its structural integrity. Moreover, the implanted sponge exhibited minimal inflammatory responses and did not cause any adverse effects on the rats' organs or behavior. Furthermore, the silk fibroin device surpassed the commercial sponge in hemorrhage control tests, demonstrating a two-fold increase in hemorrhage control in a rat bleeding model.
In addition to its hemorrhage management capabilities, the device incorporates a nanowire-based capacitive sensor for bleeding detection. When bleeding occurs, the sponge absorbs the blood, leading to an increase in its capacitance without affecting its shape. This increase in capacitance can be detected and directly corresponds to the amount of blood absorbed, enabling real-time monitoring of bleeding. Tests revealed that the device could selectively monitor blood absorption, distinguishing it from other bodily fluids that might be encountered in the wound.
Dr. Ali Khademhossein, TIBI's Director and CEO, stated, "This multifunctional device offers numerous appealing features for hemorrhage control and wound monitoring, making it highly adaptable for various types of wounds and tissues. Additionally, the hemorrhage monitoring feature opens up several possibilities for integrated biosensing and additional therapeutic applications."
Authors are: Reihaneh Haghniaz, Ankit Gangrade, Hossein Montazerian, Fahimeh Zarei, Menekse Ermis, Zijie Li, Yuxuan Du, Safoora Khosravi, Natan Roberto de Barros, Kalpana Mandal, Ahmad Rashad, Fatemeh Zehtabi, Jinghang Li, Mehmet R. Dokmeci, Han-Jun Kim, Ali Khademhosseini, Yangzhi Zhu.
This work was partially supported by the National Institutes of Health (AR074234, AR073135, HL140618, HL137193, GM126571, GM126831).
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