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Review
. 2023 Jun 13:11:1187474.
doi: 10.3389/fbioe.2023.1187474. eCollection 2023.

Development potential of extracellular matrix hydrogels as hemostatic materials

Dan Cai  1 , Wei Weng  1
Affiliations
Review

Development potential of extracellular matrix hydrogels as hemostatic materials

Dan Cai et al. Front Bioeng Biotechnol. .

Abstract

The entry of subcutaneous extracellular matrix proteins into the circulation is a key step in hemostasis initiation after vascular injury. However, in cases of severe trauma, extracellular matrix proteins are unable to cover the wound, making it difficult to effectively initiate hemostasis and resulting in a series of bleeding events. Acellular-treated extracellular matrix (ECM) hydrogels are widely used in regenerative medicine and can effectively promote tissue repair due to their high mimic nature and excellent biocompatibility. ECM hydrogels contain high concentrations of extracellular matrix proteins, including collagen, fibronectin, and laminin, which can simulate subcutaneous extracellular matrix components and participate in the hemostatic process. Therefore, it has unique advantages as a hemostatic material. This paper first reviewed the preparation, composition and structure of extracellular hydrogels, as well as their mechanical properties and safety, and then analyzed the hemostatic mechanism of the hydrogels to provide a reference for the application and research, and development of ECM hydrogels in the field of hemostasis.

Keywords: extracellular matrix components (ECM); extracellular matrix hydrogel; hemorrhage; hemostasis; hemostatic mechanism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Different derived ECM hydrogels are used for hemostasis and tissue healing. Each tissue has a unique extracellular matrix structure, and when trauma results in tissue damage and bleeding, ECM hydrogels from the same tissue source can be used to stop bleeding and promote tissue healing (Specialized hemostasis and tissue healing).
FIGURE 2
FIGURE 2
Schematic diagram of the use of ECM hydrogel showed irregular fibrous reticular scaffolds that mechanically sealed the vascular breach and formed a physical barrier.
FIGURE 3
FIGURE 3
Schematic of the complex mechanism of blood vessel hemostasis. Vessel wall rupture makes it difficult for ECM proteins to play a hemostatic role, resulting in a series of bleeding events and even death. Exogenous ECM hydrogels mimic extracellular matrix main ingredients, including collagen, laminin, fibronectin, and vitronectin, which induce platelet adhesion and activation and promote hemostasis and thrombosis.
FIGURE 4
FIGURE 4
In vitro and in vivo hemostasis test. (A) In vitro dynamic whole-blood clotting evaluation (A1, A2, and A3) of the ADM, VADM1, VADM2, VADM4, and VADM6 hydrogels, with gelatin sponge and gauze used as the control. (B) Photographs captured during the liver laceration model and renal tissue-defect model. (B1) A wound with a length of 1 cm in the liver. (B2) VADM1 hydrogel formed in situ on the trauma injury. (B3) A small portion of the kidney tissue was removed with surgical scissors. (B4) VADM1 hydrogel formed in situ on the defective tissue. (C) Photographs captured during a hemostasis test on the abdominal aorta (highlighted by red circles and ellipses). (c1) Clipped abdominal aorta. (c2,c3) Arterial spurts can be observed after release of the artery clip. (c4) VADM1 hydrogel applied to the wound. (c5) Abdominal aorta surrounded by VADM1 hydrogel. (c6) Artery clip was removed after 5 min, and the bleeding was stopped completely. The abdominal aorta was clogged with hydrogel. (c7–c9) Arterial spurts still occur on the control group after 5 min, when the artery clip was released. (D) H&E stained micrographs, showing signifificant accumulation of red cells (yellow arrow) within the incision site. Scale bar ¼ 100 μm. (E) Blood loss from liver and kidney incisions. Three replicates of each sample were tested and the data were shown as mean ± SD. VADM:acellular dermal matrix hydrogel blended with vancomycin. Reprinted from (Cai et al., 2021) with permission from Elsevier Publisher, Ltd.
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Grants and funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Zhejiang Province Public Welfare Technology Application Research Project (CN), China (Grant No. LGF20H060009).

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