Novel Biodegradable Hemostatic Nanocomposite Revolutionizes Bleeding Control and Liver Wound Healing

Researchers have developed a biodegradable nanocomposite incorporating decellularized liver extracellular matrix (L-ECM) and thrombin, demonstrating exceptional hemostatic efficiency and liver wound healing in preclinical models.

The Challenge of Hemorrhage Control

Uncontrolled bleeding during surgeries and trauma remains a leading cause of death globally, with approximately 30% of trauma-related fatalities occurring before emergency treatment can be administered. Traditional hemostatic materials, such as gauze and gelatin-based agents, often fall short in addressing deep wound injuries or vital organ trauma. These materials can be associated with risks including cytotoxicity, infection, and delayed wound healing. Consequently, there is a pressing demand for biocompatible, biodegradable materials that not only control bleeding efficiently but also promote wound healing and tissue regeneration.

New Horizons in Hemostasis

The research team from Soonchunhyang University in South Korea aimed to develop an innovative hemostatic material to address these limitations. Their novel nanocomposite, CN/CS/EM-Th, combines TEMPO-oxidized cellulose nanofiber (TOCN), chitosan (CS), liver extracellular matrix (L-ECM), and thrombin. This combination integrates the natural hemostatic properties of TOCN and chitosan with the regenerative capabilities of L-ECM and thrombin, forming a material with enhanced hemostatic efficiency and wound healing potential. Published in the International Journal of Biological Macromolecules, the study outlines a significant step forward in trauma and surgical care.

Innovative Methods for a Breakthrough Composite

The fabrication process involved creating a porous and biodegradable composite using TOCN and CS through electrostatic interactions. Freeze-drying methods were employed to incorporate L-ECM, a collagen-rich material obtained from decellularized porcine liver tissue, and thrombin, a vital coagulation agent. The resulting composite, CN/CS/EM-Th, exhibited a highly porous structure designed for rapid blood absorption and clot formation. Its biocompatibility and biodegradability were assessed through in vitro and in vivo models.

Results That Redefine Hemostasis

The study demonstrated the superior performance of CN/CS/EM-Th compared to commercially available Surgicel gauze across several key metrics:

1. Hemostasis Time in Liver Avulsion Model:
   • CN/CS/EM-Th: 41 ± 9.29 seconds
   • Surgicel: 110 ± 36.05 seconds

2. Hemostasis Time in Tail Amputation Model:
   • CN/CS/EM-Th: 71.66 ± 17.55 seconds
   • Surgicel: 222.66 ± 17.15 seconds
3. Blood Loss in Liver Avulsion Model:
   • CN/CS/EM-Th: 0.50 ± 0.23 g
   • Surgicel: 1.57 ± 0.40 g

4. Blood Loss in Tail Amputation Model:
   • CN/CS/EM-Th: 1.02 ± 0.35 g
   • Surgicel: 2.79 ± 0.40 g
5. In Vitro Degradability:
   • After 14 days in lysozyme solution, CN/CS/EM-Th retained only 16.5 ± 5.73% of its weight, demonstrating superior biodegradability compared to CN and CN/CS composites.
6. Blood Clotting Index (BCI):
   • CN/CS/EM-Th showed the lowest BCI among all tested samples, indicating faster and more efficient clotting.
7. Wound Healing Outcomes:
   • Histological analysis revealed reduced inflammation and enhanced cell infiltration at the wound site in CN/CS/EM-Th treated animals compared to Surgicel. After four weeks, CN/CS/EM-Th-treated liver wounds exhibited near-complete healing with significant fibroblast and hepatocyte presence.

Study Significance

This study successfully developed and evaluated a novel CN/CS/EM-Th nanocomposite for hemostasis and liver wound healing. The composite demonstrated:

• Rapid and efficient hemostatic performance, significantly outperforming commercial alternatives in preclinical models.
• Enhanced wound healing through reduced inflammation, increased cell infiltration, and improved liver tissue regeneration.
• Promising biodegradability and biocompatibility, critical for clinical application.

These findings establish CN/CS/EM-Th as a promising candidate for next-generation hemostatic materials, with potential applications in surgery and trauma care.

Reference:
Mahbub, Md Sowaib Ibne, et al. “Decellularized liver extracellular matrix and thrombin loaded biodegradable TOCN/Chitosan nanocomposite for hemostasis and wound healing in rat liver hemorrhage model.” International Journal of Biological Macromolecules 225 (2023): 1529-1542.