Abstract
Gelatin sponges developed by crosslinking gelatin with formaldehyde followed by controlled freeze-drying results in soft, spongy porous structures, which are useful in arresting bleeding during surgical procedures. The aim of this article is to conduct the in vivo evaluation of the gelatin sponge as per ISO 10993: Biological evaluation of medical devices; and prove its biocompatibility. The sponges were also evaluated by morphology analysis, tensile strength and blood-absorption studies. Sponges were found to be microporous with considerable mechanical strength to withstand any rupture during its application. Blood absorption studies showed good absorption behaviour. As per ISO 10993; cytotoxicity, skin irritation, sensitisation and blood compatibly studies has to be conducted to check the biocompatibility of a biomaterial. Gelatin sponge was found to be non-cytotoxic in Balb/c 3T3 cells. The experiments conducted on albino rabbits and guinea pig concluded that the material does not cause any irritation and sensitisation in vivo and is non-haemolytic when in contact with blood. Hence the material meets the requirements of a biocompatible haemostatic agent for the management of blood loss during surgical procedures.
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References
World Health Organisation, “Cause-specific Mortality and Morbidity”, http://www.who.int/whosis/whostat/EN_WHS09_Table2.pdf (Accessed March 3, 2020).
L. Holness, M. A. Knippen, L. Simmons, and P. A. Lachenbruch, Transfus. Med. Rev., 18, 184 (2004).
X. Sun, Z. Tang, M. Pan, Z. Wang, H. Yang, and H. Liu, Carbohydr. Polym., 177, 135 (2017).
W. D. Spotnitz and S. Burks, Transfusion, 48, 1502 (2008).
M. Kabiri, S. H. Emami, M. Rafienia, and M. Tahriri, Curr. Appl. Phys., 11, 457 (2011).
F. G. Torres, S. Commeaux, and O. P. T. Heros, Starch-Starke, 65, 543 (2013).
F. Cheng, C. Liu, H. Li, X. Wei, T. Yan, Y. Wang, Y. Song, J. He, and Y. Huang, Carbohydr. Polym., 183, 246 (2018).
F. Wang, S. Hu, Q. Jia, and L. Zhang, J. Nanomater., 1, 8719859 (2020).
B. Bellich, I. D’Agostino, S. Semeraro, A. Gamini, and A. Cesaro, Mar. Drugs, 14, 99 (2016).
J. Han, D. Zhao, D. Li, X. Wang, Z. Jin, and K. Zhao, Polymers, 10, 31 (2018).
J. C. Courtenay, R. I. Sharma, and J. L. Scott, Molecules, 23, 654 (2018).
S. Kaila, A. Dufresne, B. M. Cherian, B. S. Kaith, L. Averous, J. Njuguna, and E. Nassiopoulos, Int. J. Polym. Sci., 2011, 1 (2011).
R. Song, M. Murphy, C. Li, K. Ting, C. Soo, and Z. Zheng, Drug Des. Devel. Ther., 12, 3117 (2018).
S. Gorgieva and V. Kokol, “Biomaterials Applications for Nanomedicine”, IntechOpen, doi: https://doi.org/10.5772/241182011 (2011).
Drug Bank, “Gelatin”, https://www.drugbank.ca/drugs/ DB11242 (Accessed March 3, 2020).
E. M. Masutani, C. K. Kinoshita, T. T. Tanaka, A. K. D. Ellison, and B. A. Yoza, Int. J. Biomater., 1, 979636 (2014).
G. Yang, Z. Xiao, X. Ren, H. Long, H. Qian, K. Ma, and Y. Guo, Peer J., 4, e2497 (2016).
A. Bigi, G. Cojazzi, S. Panzavolta, K. Rubini, and N. Roveri, Biomaterials, 22, 763 (2001).
T. Salsa, M. E. Pina, and J. J. C. Teixeira-Dias, Appl. Spectrosc., 50, 1314 (1996).
K. Tomihata and Y. Ikada, Tissue Eng., 2, 307 (1996).
A. Bigi, G. Cojazzi, S. Panzavolta, N. Roveri, and K. Rubini, Biomaterials, 23, 4827 (2002).
G. Yang, Z. Xiao, H. Long, K. Ma, J. Zhang, X. Ren, and J. Zhang, Sci. Rep., 8, 1616 (2018).
Y. Zhao, Z. Li, W. Yang, C. Xue, Y. Wang, J. Dong, and Y. Xue, Int. J. Food Prop., 19, 731 (2016).
C. Klockenbusch and J. Kast, Biomed. Res. Int., 1, 927585 (2010).
B. W. Sutherland, J. Toews, and J. Kast, J. Mass. Spectrom., 43, 699 (2008).
H. P. Jenkins and R. Janda, Ann. Surg., 124, 952 (1946).
H. Ueno, T. Mori, and T. Fujinaga, Adv. Drug Deliv. Rev., 52, 105 (2001).
K. Ulubayram, E. Aksu, S. I. D. Gurhan, K. Serbetci, and N. Hasirci, J. Biomater. Sci. Polym. Ed., 13, 1203 (2002).
R. Imani, M. Rafienia, and S. H. Emami, Bio-Med Mater. Eng., 23, 211 (2013).
H. W. Kang, Y. Tabata, and Y. Ikada, Biomaterials, 20, 1339 (1999).
S. A. Poursamar, A. N. Lehner, M. Azami, S. Ebrahimi-Barough, A. Samadikuchaksaraei, and A. P. M. Antunes, Mater. Sci. Eng. C., 63, 1 (2016).
A. Siew, Pharm. Technol., 42, 18 (2018).
A. Gupta, IJDDR, 4, 35 (2012).
S. Kanokpanont, S. Damrongsakkul, J. Ratanavaraporn, and P. Aramwitt, Int. J. Pharm., 436, 141 (2012).
M. P. Das, P. R. Suguna, K. Prasad, J. V. Vijayalakshmi, and M. Renuka, Int. J. Pharm. Sci., 9, 239 (2017).
L. Khadidja, C. Asma, B. Mahmoud, and E. Meriem, Polym. Bull., 74, 4899 (2017).
J. S. Lee, C. Y. Hsu, and W. H. Lin, U.S. Patent, 6693180B2 (2002).
S. M. M. Alam, M. A. A. Faruque, E. Sarker, K. Sowrov, T. Alam, and A. N. M. A. Haque, Adv. Res. Text. Eng., 3, 1021 (2018).
W. Li, J. Zhou, and Y. Xu, Biomed. Rep., 3, 617 (2015).
J. P. Boutrand, “Biocompatability and Performance of Medical Devices”, 2nd ed., pp.123–166, Woodhead-Publishing, Elsevier, Cambridge, 2019.
ISO 10993-10:2010, “Biological Evaluation of Medical Devices — Part 10: Tests for Irritation and Skin Sensitization”, 2010.
P. C. K. Sankar, G. Rajmohan, and M. J. Rosemary, Mater. Lett., 208, 130 (2017).
G. A. Babitha, S. C. K. Yadav, S. D. Christopher, N. Singh, and S. Prakash, Adv. Dent. Oral Health, 7, 555707 (2017).
J. Y. Lai, D. H. K. Ma, M. H. Lai, Y. T. Li, R. J. Chang, and L. M. Chen, PLoS One, 8, e54058 (2013).
S. Thomas, J. Wound Care, 9, 56 (2000).
V. Kumar, N. Sharma, and S. S. Maitra, Int. Nano Lett., 7, 243 (2017).
M. O. Wang, J. M. Etheridge, J. A. Thompson, C. E. Vorwald, D. Dean, and J. P. Fisher, Biomacromolecules, 14, 1321 (2013).
U. T. Seyfert, V. Biehl, and J. Schenk, Biomol. Eng., 19, 91 (2002).
M. Weber, H. Steinle, S. Golombek, L. Hann, C. Schlensak, H. P. Wendel, and M. A. Adali, Front Bioeng Biotechnol., 6, 99 (2018).
M. Koseoglu, A. Hur, A. Atay, and S. Cuhadar, Biochem. Med., 21, 79 (2011).
J. K. Jackson and D. P. Derleth, Arch Dis Child Fetal Neonatal Ed., 83, F130 (2000).
R. N. Makroo, V. Raina, A. Bhatia, R. Gupta, A. Majid, U. K. Thakur, and N. L. Rosamma, Asian J. Transfus. Sci., 5, 15 (2011).
J. Timmons, Wounds UK, 5, 122 (2009).
R. F. Wallin, “A Practical Guide to ISO 10993-10: Irritation”, https://www.mddionline.com/news/practical-guide-iso-10993-10-irritation (Accessed March 3, 2020).
B. V. Reddy and S. Satyanandam, J. Glob. Trends. Pharm., 5, 1706 (2014).
R. F. Wallin, “A Practical Guide to ISO 10993-10: Sensitization”, https://www.mddionline.com/news/practical-guide-iso-10993-10-irritation (Accessed March 3, 2020).
G. M. Ko, A. Rosenkranz, C. R. A. Bertoncini, N. H. Jurkiewicz, M. G. Franco, and A. Jurkiewicz, BJPS, 46, 251 (2010).
Acknowledgements
RMJ is grateful to HLL Lifecare Limited for financial support. The authors would also like to acknowledge Nitta Gelatin India Limited for giving free gelatin raw material.
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was fully supported by HLL Lifecare Limited under the study number 14/03.
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Sneha Letha, S., Shukla, S.K., Haridas, N. et al. In vitro and In vivo Biocompatibility Evaluation of Freeze Dried Gelatin Haemostat. Fibers Polym 22, 621–628 (2021). https://doi.org/10.1007/s12221-021-0268-7
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DOI: https://doi.org/10.1007/s12221-021-0268-7