Abstract
Chitosan/gelatin (CG) composite sponges containing oxidized cellulose fibers (OF) crosslinked with tannic acid were fabricated by freeze-drying as hemostatic agents. The cellulose fibers were oxidized by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). Fourier transform infrared spectroscopy proved the formation of carboxyl groups on cellulose fibers. Addition of OF increased the swelling ratio of CG sponges. The amount of bleeding was measured after 10 s on hepatic trauma in a rat model. To assess the in vivo bio-absorbability of the samples, the sponges were implanted in the liver for 21 days and the volume of the repaired tissue was measured from histopathological analysis. The biocomposite sponge fabricated by addition of 30% OF suspension into CG solution showed the lowest amount of bleeding and the highest bio-absorbability after 21 days. The findings of this study indicate that the addition of OF into CG increased the clotting capability as well as the bio-absorbability of the biocomposite sponges.
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References
Abraham LC, Zuena E, Perez-Ramirez B, Kaplan DL (2008) Guide to collagen characterization for biomaterial studies. J Biomed Mater Res Part B Appl Biomater 87B:264–285. https://doi.org/10.1002/jbm.b.31078
Agrawal P, Soni S, Mittal G, Bhatnagar A (2014) Role of polymeric biomaterials as wound healing agents. Int J Low Extrem Wounds 13:180–190
Alam HB, Burris D, DaCorta JA, Rhee P (2005) Hemorrhage control in the battlefield: role of new hemostatic. Agents Military Med 170:63–69. https://doi.org/10.7205/milmed.170.1.63
Aydemir Sezer U, Sahin İ, Aru B, Olmez H, Yanıkkaya Demirel G, Sezer S (2019) Cytotoxicity, bactericidal and hemostatic evaluation of oxidized cellulose microparticles: structure and oxidation degree approach. Carbohydr Polym 219:87–94. https://doi.org/10.1016/j.carbpol.2019.05.005
Bagher Z et al (2019) Wound healing with alginate/chitosan hydrogel containing hesperidin in rat model. J Drug Deliv Sci Technol. https://doi.org/10.1016/j.jddst.2019.101379
Barhoum A, Pal K, Rahier H, Uludag H, Kim IS, Bechelany M (2019) Nanofibers as new-generation materials: from spinning and nano-spinning fabrication techniques to emerging applications. Appl Mater Today 17:1–35. https://doi.org/10.1016/j.apmt.2019.06.015
Chen XY, Low HR, Loi XY, Merel L, Mohd Cairul Iqbal MA (2019) Fabrication and evaluation of bacterial nanocellulose/poly (acrylic acid)/graphene oxide composite hydrogel: characterizations and biocompatibility studies for wound dressing. J Biomed Mater Res Part B 107B:2140–2151. https://doi.org/10.1002/jbm.b.34309
Cheng F, Liu C, Wei X, Yan T, Li H, He J, Huang Y (2017) Preparation and characterization of 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanocrystal/alginate biodegradable composite dressing for hemostasis applications. ACS Sustain Chem Eng 5:3819–3828
Curvello R, Raghuwanshi VS, Garnier G (2019) Engineering nanocellulose hydrogels for biomedical applications. Adv Colloid Interface Sci 267:47–61
Fathollahipour S, Mehrizi A, Ghaee A, Koosha M (2015) Electrospinning of PVA/chitosan nanocomposite nanofibers containing gelatin nanoparticles as a dual drug delivery system. J Biomed Mater Res Part A. https://doi.org/10.1002/jbm.a.35529
Fujisawa S, Okita Y, Fukuzumi H, Saito T, Isogai A (2011) Preparation and characterization of TEMPO-oxidized cellulose nanofibril films with free carboxyl groups. Carbohydr Polym 84:579–583. https://doi.org/10.1016/j.carbpol.2010.12.029
Ghafari R, Jonoobi M, Amirabad LM, Oksman K, Taheri AR (2019) Fabrication and characterization of novel bilayer scaffold from nanocellulose based aerogel for skin tissue engineering applications. Int J Biol Macromol 136:796–803. https://doi.org/10.1016/j.ijbiomac.2019.06.104
Gu BK, Park SJ, Kim MS, Lee YJ, Kim J-I, Kim C-H (2016) Gelatin blending and sonication of chitosan nanofiber mats produce synergistic effects on hemostatic functions. Int J Biol Macromol 82:89–96. https://doi.org/10.1016/j.ijbiomac.2015.10.009
Halim ALA, Kamari A, Phillip E (2018) Chitosan, gelatin and methylcellulose films incorporated with tannic acid for food packaging International. J Biol Macromol 120:1119–1126. https://doi.org/10.1016/j.ijbiomac.2018.08.169
Harkins AL, Duri S, Kloth LC, Tran CD (2014) Chitosan–cellulose composite for wound dressing material. Part 2. Antimicrobial activity, blood absorption ability, and biocompatibility. J Biomed Mater Res Part B Appl Biomater 102:1199–1206
Hu Z, Zhang D-Y, Lu S-T, Li P-W, Li S-D (2018) Chitosan-based composite materials for prospective hemostatic applications. Mar Drugs 16(8):273. https://doi.org/10.3390/md16080273
Huang H et al (2019) Degradable and bioadhesive alginate-based composites: an effective hemostatic agent. ACS Biomater Sci Eng 5:5498–5505. https://doi.org/10.1021/acsbiomaterials.9b01120
Isogai A, Saito T, Fukuzumi H (2011) TEMPO-oxidized cellulose nanofibers. Nanoscale 3:71–85. https://doi.org/10.1039/C0NR00583E
Jiang Q, Xu J, Li T, Qiao C, Li Y (2014) Synthesis and antibacterial activities of quaternary ammonium salt of gelatin. J Macromol Sci Part B 53:133–141. https://doi.org/10.1080/00222348.2013.808518
Kalantari K, Afifi AM, Jahangirian H, Webster TJ (2019) Biomedical applications of chitosan electrospun nanofibers as a green polymer—review. Carbohydr Polym 207:588–600. https://doi.org/10.1016/j.carbpol.2018.12.011
Kauvar D, Lefering R, Wade C (2006) Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma Injury Infect Criti Care 60:S3–S11
Kim GH, Im JN, Kim TH, Lee GD, Youk JH, Doh SJ (2018) Preparation and characterization of calcium carboxymethyl cellulose/chitosan blend nonwovens for hemostatic agents. Text Res J 88:1902–1911
Kono H, Fujita S (2012) Biodegradable superabsorbent hydrogels derived from cellulose by esterification crosslinking with 1, 2, 3, 4-butanetetracarboxylic dianhydride. Carbohydr Polym 87:2582–2588
Koosha M, Hamedi S (2019) Intelligent chitosan/PVA nanocomposite films containing black carrot anthocyanin and bentonite nanoclays with improved mechanical, thermal and antibacterial properties. Prog Org Coat 127:338–347. https://doi.org/10.1016/j.porgcoat.2018.11.028
Koosha M, Mirzadeh H (2015) Electrospinning, mechanical properties, and cell behavior study of chitosan/PVA nanofibers. J Biomed Mater Res Part A 103:3081–3093. https://doi.org/10.1002/jbm.a.35443
Lan G et al (2015) Chitosan/gelatin composite sponge is an absorbable surgical hemostatic agent. Colloids Surf B 136:1026–1034. https://doi.org/10.1016/j.colsurfb.2015.10.039
Li Y, Qiao C, Shi L, Jiang Q, Li T (2014) Viscosity of collagen solutions: influence of concentration, temperature, adsorption, and role of intermolecular interactions. J Macromol Sci Part B 53:893–901. https://doi.org/10.1080/00222348.2013.852059
Li L et al (2019) Preparation and the hemostatic property study of porous gelatin microspheres both in vitro and in vivo. Colloids Surf B. https://doi.org/10.1016/j.colsurfb.2019.110641
Lin N, Bruzzese C, Dufresne A (2012) TEMPO-oxidized nanocellulose participating as crosslinking aid for alginate-based sponges. ACS Appl Mater Interfaces 4:4948–4959. https://doi.org/10.1021/am301325r
LogithKumar R, KeshavNarayan A, Dhivya S, Chawla A, Saravanan S, Selvamurugan N (2016) A review of chitosan and its derivatives in bone tissue engineering. Carbohydr Polym 151:172–188. https://doi.org/10.1016/j.carbpol.2016.05.049
Mohammadkazemi F, Khademi Barangenani R, Koosha M (2019a) Development of organic–inorganic oxidized bacterial cellulose nanobiocomposites: ternary complexes. Cellulose 26:6009–6022. https://doi.org/10.1007/s10570-019-02514-w
Mohammadkazemi F, Khademibarangenani R, Koosha M (2019b) The effect of oxidation time and concentration on physicochemical, structural, and thermal properties of bacterial nano-cellulose. Polym Sci Ser A 61:265–273. https://doi.org/10.1134/S0965545X19030088
Morrissey JH et al (2010) Protein–phospholipid interactions in blood clotting. Thromb Res 125:S23–S25. https://doi.org/10.1016/j.thromres.2010.01.027
Naimer SA (2014) A review of methods to control bleeding from life-threatening traumatic wounds. Health 6:479
Nguyen VC, Nguyen VB, Hsieh M-F (2013) Curcumin-loaded chitosan/gelatin composite sponge for wound healing application. Int J Polym Sci 2013:106570. https://doi.org/10.1155/2013/106570
Osorio M, Fernández-Morales P, Gañán P, Zuluaga R, Kerguelen H, Ortiz I, Castro C (2019) Development of novel three‐dimensional scaffolds based on bacterial nanocellulose for tissue engineering and regenerative medicine: effect of processing methods, pore size, and surface area. J Biomed Mater Res Part A 107:348–359
Rubentheren V, Ward TA, Chee CY, Tang CK (2015) Processing and analysis of chitosan nanocomposites reinforced with chitin whiskers and tannic acid as a crosslinker. Carbohydr Polym 115:379–387
Shefa AA, Taz M, Hossain M, Kim YS, Lee SY, Lee B-T (2019) Investigation of efficiency of a novel, zinc oxide loaded TEMPO-oxidized cellulose nanofiber based hemostat for topical bleeding. Int J Biol Macromol 126:786–795. https://doi.org/10.1016/j.ijbiomac.2018.12.079
Sukul M, Ventura RD, Bae SH, Choi HJ, Lee SY, Lee BT (2017) Plant-derived oxidized nanofibrillar cellulose-chitosan composite as an absorbable hemostat. Mater Lett 197:150–155. https://doi.org/10.1016/j.matlet.2017.03.102
Taheri P, Jahanmardi R, Koosha M, Abdi S (2020) Physical, mechanical and wound healing properties of chitosan/gelatin blend films containing tannic acid and/or bacterial nanocellulose. Int J Biol Macromol 154:421–432
Tang A et al (2019) Nanocellulose/PEGDA aerogel scaffolds with tunable modulus prepared by stereolithography for three-dimensional cell culture. J Biomater Sci Polym Ed 30:1–18
Wei L, Sun R, Liu C, Xiong J, Qin X (2019) Mass production of nanofibers from needleless electrospinning by a novel annular spinneret. Mater Des 179:107885. https://doi.org/10.1016/j.matdes.2019.107885
Wu Y, He J, Cheng W, Gu H, Guo Z, Gao S, Huang Y (2012) Oxidized regenerated cellulose-based hemostat with microscopically gradient structure. Carbohydr Polym 88:1023–1032. https://doi.org/10.1016/j.carbpol.2012.01.058
Xu W et al (2019) On low-concentration inks formulated by nanocellulose assisted with gelatin methacrylate (gelma) for 3D printing toward wound healing application. ACS Appl Mater Interfaces 11:8838–8848
Yuan H, Chen L, Hong FF Healing (2020) A biodegradable antibacterial nanocomposite based on oxidized bacterial nanocellulose for rapid hemostasis and wound. ACS Appl Mater Interfaces 12:3382–3392. https://doi.org/10.1021/acsami.9b17732
Zhang M, Wu Y, Zhang Q, Xia Y, Li T (2011) Synthesis and characterization of gelatin-polydimethylsiloxane graft copolymers. J Appl Polym Sci 120:2130–2137. https://doi.org/10.1002/app.33391
Zhang S, Li J, Chen S, Zhang X, Ma J, He J (2019) Oxidized cellulose-based hemostatic materials Carbohydr Polym. https://doi.org/10.1016/j.carbpol.2019.115585
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This work was financially supported by the International Cooperation Research Special Fund Project (QLUTGJHZ2018001), and the Program for Scientific Research Innovation Team in Colleges and Universities of Shandong Province.
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Ranjbar, J., Koosha, M., Chi, H. et al. Novel chitosan/gelatin/oxidized cellulose sponges as absorbable hemostatic agents. Cellulose 28, 3663–3675 (2021). https://doi.org/10.1007/s10570-021-03699-9
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DOI: https://doi.org/10.1007/s10570-021-03699-9