HYALURONAN-BASED HYDROGELS WITH HEMOSTATIC PROPERTIES A.A. Boydedayev 1 , B.I. Muhitdinov 1,2 , D.M. Amonova 1 , A.S. Turaev 1 , Y.Huang 2 , I.Y. Mexmonov 1 , B.A. Sindarov 1 , M.O. Kalonova 1,3 , L.U. Makhmudov 1 , H. Wang 2 1) Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, Mirzo Ulugbek St. 83, 100125 Tashkent, Uzbekistan 2) Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai Ke Road, 201203 Shanghai, China 3) National University of Uzbekistan, 4 University St. 4, 100174 Tashkent, Uzbekistan Conventional hemostatic materials are usually bandages and gauze that stop bleeding
by direct compression. They are considered easy to manufacture and cheap. However,
these traditional hemostatic materials are unbiodegradable and prone to bacterial
infections in the presence of blood or tissue fluids. Therefore, developing hemostatic
materials with excellent biodegradable and biocompatible properties is necessary. In
this context, polysaccharide-based biomaterials have perspectives with respect to their
unique biological and pharmacological behaviors.
In this work, hyaluronan-based hydrogels were developed by chemical crosslinking
the macromolecular polysaccharide chain with the low molecular weight chitosan.
Three hydrogel samples differing in proportions of the hyaluronic acid and chitosan
crosslinker were prepared and purified by the aqueous dialysis method. The samples
obtained were systematically analyzed using IR spectroscopic, X-ray diffraction (XRD),
and SEM techniques. The hydrogels were further studied for the hemostatic and
bioabsorbility properties in the liver resection and dorsal injection rat models.
The IR spectroscopic studies of the dried samples indicated the presence of N-acetyl
group C=O bonds (1659 cm
-1
) and carboxylate C=O bonds (1633 cm
-1
). The crosslinked
macromolecular structures in the hydrogels were confirmed by the changes in the peak
intensities specific for the amide (I/II/III) bonds at 1310-1558 cm
-1
. In the XRD
analyses of the dried samples, decreases in the peaks characteristic for crystalline
regions of the parent polysaccharides were detected at 2θ=16.75°-23.6°, which occurred
due to the cross-linking of the polysaccharide chains. SEM images of the dried
hydrogels showed irregular macropores and wavy morphological structures that are
characteristic of polysaccharide-based hydrogels. In the
in vivo evaluations, liver
bleedings in the hydrogel-treated groups stopped 3.5-4.0 times faster than the control
(gauze) groups indicating that the hydrogels have good hemostatic properties.
Bioabsorbility biocompatibility studies showed complete absorption of the hydrogels
during 17-21 days and no allergic reactions or toxic effects were observed in the
animals, indicating good bioavailability and biocompatibility of the hydrogels prepared.
In conclusion, hyaluronan/chitosan crosslinked hydrogels were prepared and
characterized by chemical and morphological structures. The pharmacological
evaluations in the liver resection rat model indicated that the hydrogel samples prepared
have hemostatic properties. The histological observations showed the hydrogels are
bioabsorbable. In addition, no allergic reactions or toxic effects were observed in the
animals treated with the hydrogels. The overall results demonstrated that the hydrogels
developed are promising for the preparation of hemostatic materials.