Isolation, Characterization and Evaluation of Collagen from Jellyfish Rhopilema esculentum Kishinouye for Use in Hemostatic Applications
January
Isolation, Characterization and Evaluation of Collagen from Jellyfish Rhopilema esculentum Kishinouye for Use in Hemostatic Applications
Xiaochen Cheng 0 1
Ziyu Shao☯ 0 1
Chengbo Li☯ 0 1
Lejun Yu☯ 0 1
Mazhar Ali Raja☯ 0 1
Chenguang Liu 0 1
0 College of Marine Life Sciences, Ocean University of China , Qingdao , P. R. China
1 Editor: Ming Dao, Massachusetts Institute of Technology , UNITED STATES
Hemostat has been a crucial focus since human body is unable to control massive blood loss, and collagen proves to be an effective hemostat in previous studies. In this study, collagen was isolated from the mesoglea of jellyfish Rhopilema esculentum Kishinouye and its hemostatic property was studied. The yields of acid-soluble collagen (ASC) and pepsin-soluble (PSC) were 0.12% and 0.28% respectively. The SDS-PAGE patterns indicated that the collagen extracted from jellyfish mesoglea was type I collagen. The lyophilized jellyfish collagen sponges were cross-linked with EDC and interconnected networks in the sponges were revealed by scanning electron microscope (SEM). Collagen sponges exhibited higher water absorption rates than medical gauze and EDC/NHS cross-linking method could improve the stability of the collagen sponges. Compared with medical gauze groups, the blood clotting indexes (BCIs) of collagen sponges were significantly decreased (P < 0.05) and the concentration of collagen also had an influence on the hemostatic property (P < 0.05). Collagen sponges had an improved hemostatic ability compared to the gauze control in tail amputation rat models. Hemostatic mechanism studies showed that hemocytes and platelets could adhere and aggregate on the surface of collagen sponge. All properties make jellyfish collagen sponge to be a suitable candidate used as hemostatic material and for wound healing applications.
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Data Availability Statement: All relevant data are
within the paper and its Supporting Information
files.
Funding: The authors received no specific funding
for this work.
Competing Interests: The authors have declared
that no competing interests exist.
1. Introduction
Uncontrolled hemorrhage after trauma and in surgical procedures has associated with the
increased mortality rate, and emergency hemostatic management has been a crucial focus [1±
3]. The body's natural responses to an injury are comprised of hemostatic process and healing
of the wound site [
4
]. However, the body's natural mechanism is unable to control massive
hemorrhaging caused by major trauma or surgery. There is a medical need to develop an
effective hemostat for emergency circumstances [
5
].
Traditional hemostasis techniques (cautery and suture ligation) used in the operating
room can always cause problems such as oozing bleeding [
3
] and damaging of capillaries
resulting in tissue necrosis [
6
]. For these reasons, a number of hemostatic agents that can
arrest bleeding and promote hemostasis have been developed. Either natural or synthetic
polymers have been employed for the construction of hemostatic agents. The configurations
of these agents are mostly sheet [
7
], sponge [8±9] and glue [
10
]. Natural polymers have been
widely used as topical hemostatic agents for their excellent properties such as
biodegradability and biocompatibility.
Natural hemostatic agents such as oxidized cellulose [11±12], chitosan [9,13±14], gelatin
[
15
], thrombin [
16
], collagen [17±18] and fibrin [
19
] can be divided in active and passive
agents [
20
]. For example, fibrin glue has been widely used as active hemostatic agents which
can effectively prevent the postoperative complications such as bleeding, hematoma formation,
seroma, edema, and prolonged drainage [21±23]. However, plasma derived fibrin sealant/
hemostatic products can cause viral contamination and anaphylaxis [24±25]. Horowitz and
Busch have reported that the fibrin sealants have some risks of transmission of HIV, hepatitis
virus and other parvovirus [
26
]. Passive hemostatics, including collagen, gelatin and oxidized
cellulose, are not biologically active; their mechanism of action is to provide platelet activation
and aggregation [
3
]. Among them, collagen has been reported as useful hemostatic agent [27±
30]. Collagen is the most abundant protein (approximately 30% by weight of total protein) in
human's body which consists in extracellular matrix [
31
]. The triple helical structures exist in
all collagen molecules and form three parallel, left-handed helical polypeptide α-chains [
32
].
Each α-chain has a characteristic [Gly-X-Y] domain repeat, in which X and Y mostly represent
the proline (Pro) and hydroxyproline (HyP) [
33
]. Moreover, it has been proved that collagen
has better biocompatibility, higher biodegradability, lower antigenicity and cell-binding
properties as a natural protein, which can be degraded into physiologically tolerable compounds in
vivo. [34±36]. The role of collagen in regulation of hemostasis is that (...truncated)