Conventional self-assembling peptide hydrogels are effective as topical hemostatic agents. However, there is a possibility to harm living tissues due to their low pH. The aim of the present study was to demonstrate the efficacy of SPG-178, a neutral self-assembling peptide hydrogel, as a topical hemostatic agent. First, we measured the bleeding duration of incisions made on rat livers after application of SPG-178 (1.0% w/v), SPG-178 (1.5% w/v), RADA16 (1.0% w/v), and saline (n = 12/group). Second, we observed the bleeding surfaces by transmission electron microscopy immediately after hemostasis. Third, we measured the elastic and viscous responses (G′ and G″, respectively) of the hydrogels using a rheometer. Our results showed that bleeding duration was significantly shorter in the SPG-178 group than in the RADA16 group and that there were no significant differences in transmission electron microscopy findings between the groups. The greater the G′ value of a hydrogel, the shorter was the bleeding duration. We concluded that SPG-178 is more effective and has several advantages: it is non-biological, transparent, nonadherent, and neutral and can be sterilized by autoclaving.
References
[1]
Carson JL, Poses RM, Spence RK, Bonavita G (1988) Severity of anaemia and operative mortality and morbidity. Lancet 1: 727–729. doi: 10.1016/s0140-6736(88)91536-x
[2]
Wu WC, Trivedi A, Friedmann PD, Henderson WG, Smith TS, et al. (2012) Association between hospital intraoperative blood transfusion practices for surgical blood loss and hospital surgical mortality rates. Ann Surg 255: 708–714. doi: 10.1097/sla.0b013e31824a55b9
[3]
Achneck HE, Sileshi B, Jamiolkowski RM, Jamiolkowski RM, Albala DM, et al. (2010) A comprehensive review of topical hemostatic agents: efficacy and recommendations for use. Ann Surg 251: 217–228. doi: 10.1097/sla.0b013e3181c3bcca
[4]
Emilia M, Luca S, Francesca B, Luca B, Paolo S, et al. (2011) Topical hemostatic agents in surgical practice. Transfus Apher Sci 45: 305–311. doi: 10.1016/j.transci.2011.10.013
[5]
Lang CJ, Heckmann JG, Neund？rfer B (1998) Creutzfeldt-Jakob disease via dural and corneal transplants. J Neurol Sci 160: 128–39. doi: 10.1016/s0022-510x(98)00226-3
[6]
Yasunaga H (2007) Risk of authoritarianism: fibrinogen-transmitted hepatitis C in Japan. Lancet 370: 2063–2067. doi: 10.1016/s0140-6736(07)61867-4
[7]
Ellis-Behnke RG, Liang YX, Tay DK, Kau PW, Schneider GE, et al. (2006) Nano hemostat solution: immediate hemostasis at the nanoscale. Nanomedicine 2: 207–215. doi: 10.1016/j.nano.2006.08.001
[8]
Zhang S, Holmes T, Lockshin C, Rich A (1993) Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proc Natl Acad Sci USA 90: 3334–3338. doi: 10.1073/pnas.90.8.3334
[9]
Zhang S, Holems TC, DiPersio CM, Hynes RO, Su X, et al. (1995) Self-complementary oligopeptide matrices support mammalian cell attachment. Biomaterials 16: 1385–1393. doi: 10.1016/0142-9612(95)96874-y
[10]
Yokoi H, Kinoshita T, Zhang S (2005) Dynamic reassembly of peptide RADA16 nanofiber scaffold. Proc Natl Acad Sci USA 102: 8414–8419. doi: 10.1073/pnas.0407843102
[11]
Song H, Zhang L, Zhao X (2010) Hemostatic efficacy of biological self-assembling peptide nanofibers in a rat kidney model. Macromol Biosci 10: 33–39. doi: 10.1002/mabi.200900129
[12]
Luo Z, Wang S, Zhang S (2011) Fabrication of self-assembling D-form peptide nanofiber scaffold d-EAK16 for rapid hemostasis. Biomaterials 32: 2013–2020. doi: 10.1016/j.biomaterials.2010.11.049
[13]
Masuhara H, Fujii T, Watanabe Y, Koyama N, Tokuhiro K (2012) Novel infectious agent-free hemostatic material (TDM-621) in cardiovascular surgery. Ann Thorac Cardiovasc Surg 18: 444–451. doi: 10.5761/atcs.oa.12.01977
[14]
Semino CE, Merok JR, Crane GG, Panaqiotakos G, Zhang S (2003) Functional differentiation of hepatocyte-like spheroid structures form putative liver progenitor cells in three-dimensional peptide scaffolds. Differentiation 71: 262–270. doi: 10.1046/j.1432-0436.2003.7104503.x
[15]
Genové E, Shen C, Zhang S, Semino CE (2005) The effect of functionalized self-assembling peptide scaffolds on human aortic endothelial cell function. Biomaterials 26: 3341–3351. doi: 10.1016/j.biomaterials.2004.08.012
[16]
Davis ME, Motion JPM, Narmoneva DA, Takahashi T, Hakuno D, et al. (2005) Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation 111: 442–450. doi: 10.1161/01.cir.0000153847.47301.80
[17]
Holmes TC, de Lacalle S, Su X, Liu G, Rich A, et al. (2000) Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. Proc Natl Acad Sci USA 97: 6728–6733. doi: 10.1073/pnas.97.12.6728
[18]
Nagai Y, Unsworth LD, Koutsopoulos S, Zhang S (2006) Slow release of molecules in self-assembling peptide nanofiber scaffold. J Control Release 115: 18–25. doi: 10.1016/j.jconrel.2006.06.031
[19]
Koutsopoulos S, Unsworth LD, Nagai Y, Zhang S (2008) Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold. Proc Natl Acad Sci USA 106: 4623–4628. doi: 10.1073/pnas.0807506106
[20]
Schneider A, Garlick JA, Egles C (2008) Self-assembling peptide nanofiber scaffolds accelerate wound healing. PloS One 3: e1410. doi: 10.1371/journal.pone.0001410
[21]
Meng H, Chen L, Ye Z, Wang S, Zhao X (2009) The effect of a self-assembling peptide nanofiber scaffold (peptide) when used as a wound dressing for the treatment of deep second degree burns in rats. J Biomed Mater Res B Appl Biomater 89: 379–391. doi: 10.1002/jbm.b.31226
[22]
Leugn GKK, Wang YC (2012) Wu Wutian (2012) Peptide nanofiber for brain tissue reconstruction. Methods Enzymol 508: 177–190. doi: 10.1016/b978-0-12-391860-4.00009-4
[23]
Liedmann A, Rolf A, Frech MJ (2012) Cultivation of human neural progenitor cells in a 3-dimensional self-assembling peptide hydrogel. J. Vis. Exp 59: e3830. doi: 10.3791/3830
[24]
Akiyama N, Yamamoto-Fukuda T, Takahashi H, Koji T (2013) In situ tissue engineering with synthetic self-assembling peptide nanofiber scaffolds, PuraMatrix, for mucosal regeneration in the rat middle-ear. Int J Nanomedicine 8: 2629–2640. doi: 10.2147/ijn.s47279
[25]
Kim MS, Yeon JH, Park JK (2007) A microfluidic platform for 3-dimensional cell culture and cell-based assays. Biomed Microdevices 9: 25–34. doi: 10.1007/s10544-006-9016-4
[26]
Um E, Lee DS, Pyo HB, Park JK (2008) Continuous generation of hydrogel beads and encapsulation of biological materials using a microfluidic droplet-merging channel. Microfluid Nanofluid 5: 541–549. doi: 10.1007/s10404-008-0268-6
[27]
Shivachar AC (2008) Isolation and culturing of glial, neuronal and neural stem cell types encapsulated in biodegradable peptide hydrogel. Topics in tissue engineering 4 : chapter 8.
[28]
Moradi F, Bahktiari M, Joghataei MT, Nobakht M, Soleimani M, et al. (2012) BD PuraMatrix peptide hydrogel as a culture system for human fetal schwann cells in spinal cord regeneration. J. Neurosci. Res 90: 2335–2348. doi: 10.1002/jnr.23120
[29]
Guo J, Su H, Zeng Y, Liang YX, Wong WM, et al. (2007) Reknitting the injured spinal cord by self-assembling peptide nanofiber scaffold. Nanomedicine 3: 311–321. doi: 10.1016/j.nano.2007.09.003
[30]
Dégano IR, Quintana L, Vilalta M, Horna D, Rubio N, et al. (2009) The effect of self-assembling peptide nanofiber scaffolds on mouse embryonic fibroblast implantation and proliferation. Biomaterials 30: 1156–1165. doi: 10.1016/j.biomaterials.2008.11.021
[31]
Zhao Y, Yokoi H, Tanaka M, Kinoshita T, Tan T (2008) Self-assembled pH-responsive hydrogels composed of the RATEA16 peptide. Biomacromolecules 9: 1511e8. doi: 10.1021/bm701143g
[32]
Nagai Y, Yokoi H, Kaihara K, Naruse K (2012) The mechanical stimulation of cells in 3D culture within a self-assembling peptide hydrogel. Biomaterials 33: 1044–1051. doi: 10.1016/j.biomaterials.2011.10.049
[33]
Cylwik D, Mogielnicki A, Kramkowski K, Stokowski J, Buczko W (2004) Antithrombotic effect of L-arginine in hypertensive rats. J Physiol Pharmacol 55: 563–74.
