Novel hemostatic agents based on gelatin-microbial transglutaminase mix
Hemostasis is a major challenge in surgical procedures and traumas. Conventional hemostatic methods have limited efficacy and may cause additional tissue damage. In this study, we designed a novel hemostatic agent based on the in situ gel formation of gelatin cross-linked by a novel microbial transglutaminase (mTGase), in which the amino acid sequences differed from commercial mTGases. The new hemostatic agent showed the same biochemical crosslinking chemistry as the final stages of the blood coagulation cascade while using gelatin as a “structural” protein (rather than fibrin) and a calcium-independent mTGase as the crosslinking catalyst (rather than factor XIIIa). In rat liver hemostasis models, the hemostatic agent not only showed a similar hemostatic effect as that of SURGIFLO® (positive control), but also stronger adhesion strength and elasticity than SURGIFLO®. Therefore, this biomimetic gelatin-mTGase mix hemostatic is a novel and effective surgical sealant.
Keywordsmicrobial transglutaminase gelatin crosslinking biomimetic hemostatic
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This work was supported by the Major State Basic Research Development Program of China (2015CB910400, 2012CB910400), and National Natural Science Foundation of China (81472788, 81272463, 81330049).
- Carraway, J.W., Kent, D., Young, K., Cole, A., Friedman, R., and Ward, K.R. (2008). Comparison of a new mineral based hemostatic agent to a commercially available granular zeolite agent for hemostasis in a swine model of lethal extremity arterial hemorrhage. Resuscitation 78, 230–235.CrossRefPubMedGoogle Scholar
- Chen, T., Janjua, R., McDermott, M.K., Bernstein, S.L., Steidl, S.M., and Payne, G.F. (2006). Gelatin-based biomimetic tissue adhesive. Potential for retinal reattachment. J Biomed Mater Res 77B, 416–422.Google Scholar
- Lang, H., Mouracade, P., Gimel, P., Bernhard, J.C., Pignot, G., Zini, L., Crepel, M., Rigaud, J., Salomon, L., Bellec, L., Vaessen, C., Roupret, M., Jung, J.L., Mourey, E., Martin, X., Bigot, P., Bruyère, F., Berger, J., Ansieau, J.P., Salome, F., Hubert, J., Pfister, C., Trifard, F., Gigante, M., Baumert, H., Méjean, A., and Patard, J.J. (2014). National prospective study on the use of local haemostatic agents during partial nephrectomy. BJU Int 113, E56–E61.CrossRefPubMedGoogle Scholar
- Sahoo, N., Sahoo, R.K., Biswas, N., Guha, A., and Kuotsu, K. (2015). Recent advancement of gelatin nanoparticles in drug and vaccine delivery.Google Scholar
- Int J Biol Macromol 81, 317–331.Google Scholar
- Shen, Y., Dai, L., Li, X., Liang, R., Guan, G., Zhang, Z., Cao, W., Liu, Z., Mei, S., Liang, W., Qin, S., Xu, J., and Chen, H. (2014). Epidermal stem cells cultured on collagen-modified chitin membrane induce in situ tissue regeneration of full-thickness skin defects in mice. PLoS ONE 9, e87557.CrossRefPubMedPubMedCentralGoogle Scholar
- Wu, X., Ren, J., Wang, G., Wang, J., Wang, F., Fan, Y., Li, Y., Han, G., Zhou, Y., Song, X., Quan, B., Yao, M., and Li, J. (2015). Evaluating the use of fibrin glue for sealing low-output enterocutaneous fistulas: study protocol for a randomized controlled trial. Trials 16, 445.CrossRefPubMedPubMedCentralGoogle Scholar