Evaluation of hydrogels for soft tissue adhesives in vitro and in vivo analyses

Abstract

In this study, natural materials (sodium alginate, dextran, gelatin and carboxymethyl chitosan) were modified to get aldehyde components and amino components. Upon mixing the two-component solutions together, four kinds of Schiff base hydrogels formed successfully within 5–300 s and could seal the wound tissue. The cytotoxicity tests of hydrogel extraction solution confirmed that the hydrogels are nontoxic materials. The adhesive ability was evaluated in vivo by measuring the adhesive strength after sealing the skin incisions on the back of rats. All the hydrogels showed higher adhesive strength than that of commercial fibrin glue and the blank control. The histological staining observation by hematoxylin and eosin staining (HE) and Masson’s trichrome staining (MTC) methods suggested that the hydrogels had good biocompatibility and biodegradation in vivo. They have only normal initial inflammation to skin tissue and could improve the formation of new collagen in the incision section. So, the prepared hydrogels were both safe and effective tissue adhesive, which had the great potentials to be used as skin tissue adhesive.

Keywords

Schiff’s base / injectable / hydrogels / tissue adhesive

References

[1] Stussman B J. National Hospital Ambulatory Medical Care Survey: 1994 emergency department summary. Advance Data, 1996, 275(275): 1–20

[2] Kjaergard H K. Suture support: is it advantageous? American Journal of Surgery, 2001, 182(2Suppl): 15S–20S

[3] Spotnitz W D, Falstrom J K, Rodeheaver G T. The role of sutures and fibrin sealant in wound healing. Surgical Clinics of North America, 1997, 77(3): 651–669

[4] Kaushik S, Jain R. A study on the role of tissue adhesives in tympanoplasty. Journal of Evolution of Medical and Dental Sciences, 2017, 6(25): 2101–2104

[5] Plat V D, Bootsma B T, van der Wielen N, . The role of tissue adhesives in esophageal surgery, a systematic review of literature. International Journal of Surgery, 2017, 40: 163–168

[6] Reece T B, Maxey T S, Kron I L. A prospectus on tissue adhesives. American Journal of Surgery, 2001, 182(2): S40–S44

[7] Vakalopoulos K A, Daams F, Wu Z, . Tissue adhesives in gastrointestinal anastomosis: a systematic review. The Journal of Surgical Research, 2013, 180(2): 290–300

[8] Bochyńska A I, Hannink G, Grijpma D W, . Tissue adhesives for meniscus tear repair: an overview of current advances and prospects for future clinical solutions. Journal of Materials Science: Materials in Medicine, 2016, 27(5): 85 (18 pages)

[9] Toriumi D M, Raslan W F, Friedman M, . Histotoxicity of cyanoacrylate tissue adhesives: a comparative study. Archives of Otolaryngology- Head & Neck Surgery, 1990, 116(5): 546–550

[10] Gemma P, Sandra S, Marta R, . Cytotoxicity of cyanoacrylate-based tissue adhesives and short-term preclinical in vivo biocompatibility in abdominal hernia repair. PLoS One, 2016, 11(6): e0157920

[11] Bhat Y M, Banerjee S, Barth B A, . Tissue adhesives: cyanoacrylate glue and fibrin sealant. Gastrointestinal Endoscopy, 2013, 78(2): 209–215

[12] Nguyen L P, Wang Z, Molina J, . Complications of fibrin glue in pterygium surgery with amniotic membrane transplant. Eye Science, 2012, 27(1): 19–24

[13] Piechotta F U, Flemming I. The maximization of wound healing with fibrin glue. Aesthetic Plastic Surgery, 1983, 7(2): 81–82

[14] Currie L J, Sharpe J R, Martin R. The use of fibrin glue in skin grafts and tissue-engineered skin replacements: a review. Plastic and Reconstructive Surgery, 2001, 108(6): 1713–1726

[15] Lih E, Lee J S, Park K M, . Rapidly curable chitosan-PEG hydrogels as tissue adhesives for hemostasis and wound healing. Acta Biomaterialia, 2012, 8(9): 3261–3269

[16] Ryu J H, Lee Y, Kong W H, . Catechol-functionalized chitosan/pluronic hydrogels for tissue adhesives and hemostatic materials. Biomacromolecules, 2011, 12(7): 2653–2659

[17] Mo X, Iwata H, Matsuda S, . Soft tissue adhesive composed of modified gelatin and polysaccharides. Journal of Biomaterials Science: Polymer Edition, 2000, 11(4): 341–351

[18] Taguchi T, Saito H, Uchida Y, . Bonding of soft tissues using a novel tissue adhesive consisting of a citric acid derivative and collagen. Materials Science and Engineering C, 2004, 24(6–8): 775–780

[19] Smith T J, Kennedy J E, Higginbotham C L. Rheological and thermal characteristics of a two phase hydrogel system for potential wound healing applications. Journal of Materials Science, 2010, 45(11): 2884–2891

[20] Geng X, Mo X, Fan L, . Hierarchically designed injectable hydrogel from oxidized dextran, amino gelatin and 4-arm poly(ethylene glycol)-acrylate for tissue engineering application. Journal of Materials Chemistry, 2012, 22(48): 25130–25139

[21] Yuan L, Wu Y, Fang J, . Modified alginate and gelatin cross-linked hydrogels for soft tissue adhesive. Artificial Cells, Nanomedicine, and Biotechnology, 2017, 45(1): 76–83

[22] Wu Y, Yuan L, Sheng N, . A soft tissue adhesive based on aldehyde-sodium alginate and amino-carboxymethyl chitosan preparation through the Schiff reaction. Frontiers of Materials Science, 2017, 11(3): 215–222

[23] Yuan L, Wu Y, Gu Q S, . Injectable photo crosslinked enhanced double-network hydrogels from modified sodium alginate and gelatin. International Journal of Biological Macromolecules, 2017, 96: 569–577

[24] Richardson R RJr, Miller J A, Reichert W M. Polyimides as biomaterials: preliminary biocompatibility testing. Biomaterials, 1993, 14(8): 627–635

[25] Oshima H, Nakamura M. A study on reference standard for cytotoxicity assay of biomaterials. Bio-Medical Materials and Engineering, 1994, 4(4): 327–332

[26] LeMaire S A, Carter S A, Won T, . The threat of adhesive embolization: BioGlue leaks through needle holes in aortic tissue and prosthetic grafts. The Annals of Thoracic Surgery, 2005, 80(1): 106–111

[27] Laurens N, Koolwijk P, de Maat M P. Fibrin structure and wound healing. Journal of Thrombosis and Haemostasis, 2006, 4(5): 932–939

[28] Azuma K, Izumi R, Osaki T, . Chitin, chitosan, and its derivatives for wound healing: old and new materials. Journal of Functional Biomaterials, 2015, 6(1): 104–142

[29] Guo S, Dipietro L A. Factors affecting wound healing. Journal of Dental Research, 2010, 89(3): 219–229

[30] Eming S A, Krieg T, Davidson J M. Inflammation in wound repair: molecular and cellular mechanisms. The Journal of Investigative Dermatology, 2007, 127(3): 514–525

[31] Gurtner G C, Werner S, Barrandon Y, . Wound repair and regeneration. Nature, 2008, 453(7193): 314–321

[32] Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clinics in Dermatology, 2007, 25(1): 9–18

[33] Lin P H, Hirko M K, von Fraunhofer J A, . Wound healing and inflammatory responses to biomaterials. In: Chu C C, von Fraunhofer J A, Greisler H P, et al., eds. Wound Closure Biomaterials and Devices. Boca Raton, USA: CRC Press, 1997, 7–24

[34] Değim Z, Celebi N, Sayan H, . An investigation on skin wound healing in mice with a taurine-chitosan gel formulation. Amino Acids, 2002, 22(2): 187–198

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature