Hemorrhaging often occurs during cardiac surgery, and postoperative bleeding is associated with medical complications or even death. Medical complications resulting from hemorrhaging can lead to longer hospital stays, thus increasing costs. Hemostatic agents are the main treatment for bleeding. In the present study, hemostatic agents composed of aldehyde groups and hydrophobically modified with hyaluronic acid (ald-hm-HyA) and hydrophobically modified gelatin (hm-ApGltn) were developed and their hemostatic effects were evaluated. These modified hemostatic agents formed more stable blood clots compared with the nonhydrophobically modified HyA-based hemostatic agent. The bulk strength of the whole blood clot using the aldehyde and stearoyl group-modified hyaluronic acid (ald-C18-HyA)/hm-ApGltn-based hemostatic agent was higher than that of the aldehyde group only modified HyA (ald-HyA)/hm-ApGltn-based hemostatic agent. Rheological experiments using α-cyclodextrin showed that hydrophobic modification of HyA with C18 groups effectively enhanced anchoring to the red blood cell surface. Therefore, the ald-hm-HyA/hm-ApGltn-based hemostatic agent has potential applications in cardiac surgery.
OzMCCosgroveDMBaddukeBRet al.
Controlled clinical trial of a novel hemostatic agent in cardiac surgery. Ann Thorac Surg2000;
69: 1376–1382.
3.
PalmMDAltmanJS.Topical hemostatic agents: A review. Dermatol Surg2008;
34: 431–445.
4.
BarnardJMillnerR.A review of topical hemostatic agents for use in cardiac surgery. Ann Thorac Surg2009;
88: 1377–1383.
5.
di LenaF.Hemostatic polymers: The concept, state of the art and perspectives. J Mater Chem B2014;
2: 3567–3577.
6.
LanGLuBWangTet al.
Chitosan/gelatin composite sponge is an absorbable surgical hemostatic agent. Colloids Surf B2015;
136: 1026–1034.
7.
ChungY-JAnS-YYeonJ-Yet al.
Effect of a chitosan gel on hemostasis and prevention of adhesion after endoscopic sinus surgery. Clin Exp Otorhinolaryngol2016;
9: 143–149.
8.
SamudralaS.Topical hemostatic agents in surgery: A surgeon’s perspective. AORN J2008;
88: S2–S11.
9.
PetersenBBarkunACarpenterSet al.
Tissue adhesives and fibrin glues.Gastrointest Endosc2004;
60: 327–333.
10.
TrabattoniDMontorsiPFabbiocchiFet al.
A new kaolin-based haemostatic bandage compared with manual compression for bleeding control after percutaneous coronary procedures. Eur Radiol2011;
21: 1687–1691.
11.
LammRJLimEBWeigandtKMet al.
Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer. Biomaterials2017;
132: 96–104.
12.
ChanLWKimCHWangXet al.
PolySTAT-modified chitosan gauzes for improved hemostasis in external hemorrhage. Acta Biomater2016;
31: 178–185.
13.
ChanKYTZhaoCSirenEMJet al.
Adhesion of blood clots can be enhanced when copolymerized with a macromer that is crosslinked by coagulation factor XIIIa. Biomacromolecules2016;
17: 2248–2252.
ItoMTaguchiT.Enhanced insulin secretion of physically crosslinked pancreatic β-cells by using a poly(ethylene glycol) derivative with oleyl groups. Acta Biomater2009;
5: 2945–2952.
16.
TaguchiTRaoZItoMet al.
Induced albumin secretion from HepG2 spheroids prepared using poly(ethylene glycol) derivative with oleyl groups. J Mater Sci: Mater Med2011;
22: 2357.
17.
DowlingMBKumarRKeiblerMAet al.
A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action. Biomaterials2011;
32: 3351–3357.
18.
DowlingMBMacIntireICWhiteJCet al.
Sprayable foams based on an amphiphilic biopolymer for control of hemorrhage without compression. ACS Biomater Sci Eng2015;
1: 440–447.
19.
JavvajiVDowlingMBOhHet al.
Reversible gelation of cells using self-assembling hydrophobically-modified biopolymers: Towards self-assembly of tissue. Biomater Sci2014;
2: 1016–1023.
20.
FujitaYKitagawaMNakamuraSet al.
CD44 signaling through focal adhesion kinase and its anti-apoptotic effect. FEBS Lett2002;
528: 101–108.
21.
GerechtSBurdickJAFerreiraLSet al.
Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proc Natl Acad Sci USA2007;
104: 11298–11303.
22.
MizunoYMizutaRHashizumeMet al.
Enhanced sealing strength of a hydrophobically-modified Alaska Pollock gelatin-based sealant. Biomater Sci2017;
5: 982–989.
23.
MizutaRItoTTaguchiT.Effect of alkyl chain length on the interfacial strength of surgical sealants composed of hydrophobically-modified Alaska-Pollock-derived gelatins and poly(ethylene)glycol-based four-armed crosslinker. Colloids Surf B2016;
146: 212–220.
24.
MizutaRTaguchiT.Enhanced sealing by hydrophobic modification of Alaska Pollock-derived gelatin-based surgical sealants for the treatment of pulmonary air leaks. Macromol Biosci2017;
17: 1600349.
25.
TaguchiTMizutaRItoTet al.
Robust sealing of blood vessels with cholesteryl group-modified, Alaska Pollock-derived gelatin-based biodegradable sealant under wet conditions. J Biomed Nanotechnol2016;
12: 128–134.
26.
CenniECiapettiGSteaSet al.
Biocompatibility and performance in vitro of a hemostatic gelatin sponge. J Biomater Sci Polym Ed2000;
11: 685–699.
27.
ItoTYeoYHighleyCBet al.
The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives. Biomaterials2007;
28: 975–983.
28.
LiLWangNJinXet al.
Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention. Biomaterials2014;
35: 3903–3917.
29.
RuhelaDRiviereKSzokaFC.Efficient synthesis of an aldehyde functionalized hyaluronic acid and its application in the preparation of hyaluronan−lipid conjugates. Bioconjugate Chem2006;
17: 1360–1363.
30.
BorchRFHassidAI.New method for the methylation of amines. J Org Chem1972;
37: 1673–1674.
31.
DesbrièresJMartinezCRinaudoM.Hydrophobic derivatives of chitosan: Characterization and rheological behaviour. Int J Biol Macromol1996;
19: 21–28.
32.
BouhadirKHHausmanDSMooneyDJ.Synthesis of cross-linked poly(aldehyde guluronate) hydrogels. Polymer1999;
40: 3575–3584.
33.
ZhaoHHeindelND.Determination of degree of substitution of formyl groups in polyaldehyde dextran by the hydroxylamine hydrochloride method. Pharmaceut Res1991;
8: 400–402.
34.
MorçölTSubramanianAVelanderWH.Dot-blot analysis of the degree of covalent modification of proteins and antibodies at amino groups. J Immunol Methods1997;
203: 45–53.
35.
BrowningMBCosgriff-HernandezE.Development of a biostable replacement for PEGDA hydrogels. Biomacromolecules2012;
13: 779–786.
36.
JancarJHoyRSLesserAJet al.
Effect of particle size, temperature, and deformation rate on the plastic flow and strain hardening response of PMMA composites. Macromolecules2013;
46: 9409–9426.
37.
WangQMynarJLYoshidaMet al.
High-water-content mouldable hydrogels by mixing clay and a dendritic molecular binder. Nature2010;
463: 339–343.
38.
ImaizumiYGodaTToyaYet al.
Oleyl group-functionalized insulating gate transistors for measuring extracellular pH of floating cells. Sci Technol Adv Mater2016;
17: 337–345.
39.
KatoKUmezawaKFuneriuDPet al.
Immobilized culture of nonadherent cells on an oleyl poly(ethylene glycol) ether-modified surface. BioTechniques2003;
35: 1014-8–1020-1.
40.
HochmuthRMEvansCAWilesHCet al.
Mechanical measurement of red cell membrane thickness. Science1983;
220: 101–102.
41.
DodgeJTPhillipsGB.Composition of phospholipids and of phospholipid fatty acids and aldehydes in human red cells. J Lipid Res1967;
8: 667–675.
42.
SchaeferEJRobinsSJPattonGMet al.
Red blood cell membrane phosphatidylethanolamine fatty acid content in various forms of retinitis pigmentosa. J Lipid Res1995;
36: 1427–1433.
43.
van de ManakkerFVermondenTvan NostrumCFet al.
Cyclodextrin-based polymeric materials: Synthesis, properties, and pharmaceutical/biomedical applications. Biomacromolecules2009;
10: 3157–3175.
44.
KatoKItohCYasukouchiTet al.
Rapid protein anchoring into the membranes of Mammalian cells using oleyl chain and poly(ethylene glycol) derivatives. Biotechnol Prog2004;
20: 897–904.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
