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Research Article

Highly efficient artificial blood coagulation shortcut confined on Ca-zeolite surface

Lisha Yu1,§, Bin Yu1,§, Hao Chen1, Xiaoqiang Shang1, Min He2, Mengchi Lin1, Dan Li1, Wenzhao Zhang1, Zhengzhong Kang1, Jiachen Li1, Fangjun Wang2, Liping Xiao1, Qi Wang1( ), Jie Fan1( )
Department of Chemistry, Zhejiang University, Hangzhou 310027, China
CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China

§ Lisha Yu and Bin Yu contributed equally to this work.

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Abstract

It is challenging to develop an in vitro catalytic system to conduct natural surface-confined enzymatic reactions in a stable, efficient, and spatially defined manner. Here, we report that an artificial catalyst, which composes of trypsin and a calcium ion exchanged zeolite Y (trypsin/CaY), is capable of conducting surface-confined thrombin generation, and then constructs an artificial shortcut for classic, natural and complex blood coagulation cascade. The Ca2+ within the microporous cages play a key role in trypsin/CaY hybrid through tuning the bio-inorganic interaction and spatial orientation of the protease, which allows trypsin/CaY to display greatly enhanced catalytic performance in coagulation process. The in vivo efficiency of the artificial coagulation shortcut is further confirmed in massive bleeding and hemophilia animal models. Rapid hemostasis is achieved by trypsin/CaY hybrid in a hemophilia A mice tail bleeding model, where natural clotting system fails in response to bleeding event due to factor VIII deficiency. In a rabbit lethal femoral artery injury model, the blood loss of the artificial catalyst is decreased by 4-7 fold when compared to state-of-art clay- or zeolite-based topical agents.

Keywords

surface-confinedCa-zeoliteblood coagulationtrypsin

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References

[1]
Küchler, A.; Yoshimoto, M.; Luginbuhl, S.; Mavelli, F.; Walde, P. Enzymatic reactions in confined environments. Nat. Nanotechnol. 2016, 11, 409-420.
Google Scholar
[2]
Chapin, J. C.; Hajjar, K. A. Fibrinolysis and the control of blood coagulation. Blood Rev. 2015, 29, 17-24.
Google Scholar
[3]
Vogler, E. A.; Siedlecki, C. A. Contact activation of blood-plasma coagulation. Biomaterials 2009, 30, 1857-1869.
Google Scholar
[4]
Hanefeld, U.; Gardossi, L.; Magner, E. Understanding enzyme immobilisation. Chem. Soc. Rev. 2009, 38, 453-468.
Google Scholar
[5]
Sheldon, R. A.; van Pelt, S. Enzyme immobilisation in biocatalysis: Why, what and how. Chem. Soc. Rev. 2013, 42, 6223-6235.
Google Scholar
[6]
Fu, J. L.; Liu, M. H.; Liu, Y.; Woodbury, N. W.; Yan, H. Interenzyme substrate diffusion for an enzyme cascade organized on spatially addressable DNA nanostructures. J. Am. Chem. Soc. 2012, 134, 5516-5519.
Google Scholar
[7]
Tabaei, S. R.; Rabe, M.; Zetterberg, H.; Zhdanov, V. P.; Höök, F. Single lipid vesicle assay for characterizing single-enzyme kinetics of phospholipid hydrolysis in a complex biological fluid. J. Am. Chem. Soc. 2013, 135, 14151-14158.
Google Scholar
[8]
Johnson, B. J.; Algar, W. R.; Malanoski, A. P.; Ancona, M. G.; Medintz, I. L. Understanding enzymatic acceleration at nanoparticle interfaces: Approaches and challenges. Nano Today 2014, 9, 102-131.
Google Scholar
[9]
Dahlbäck, B. Blood coagulation. Lancet 2000, 355, 1627-1632.
Google Scholar
[10]
Versteeg, H. H.; Heemskerk, J. W. M.; Levi, M.; Reitsma, P. H. New fundamentals in hemostasis. Physiol. Rev. 2013, 93, 327-358.
Google Scholar
[11]
Krishnaswamy, S. The transition of prothrombin to thrombin. J. Thromb. Haemost. 2013, 11, 265-276.
Google Scholar
[12]
Monroe, D. M.; Hoffman, M.; Roberts, H. R. Platelets and thrombin generation. Arterioscler., Thromb., Vasc. Biol. 2002, 22, 1381-1389.
Google Scholar
[13]
Young, G.; Sørensen, B.; Dargaud, Y.; Negrier, C.; Brummel-Ziedins, K.; Key, N. S. Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: Current state of art and future perspectives. Blood 2013, 121, 1944-1950.
Google Scholar
[14]
Blajchman, M. A. Substitutes and alternatives to platelet transfusions in thrombocytopenic patients. J. Thromb. Haemost. 2003, 1, 1637-1641.
Google Scholar
[15]
Shin, M.; Park, S.; Oh, B. C.; Kim, K.; Jo, S.; Lee, M. S.; Oh, S. S.; Hong, S. H.; Shin, E. C.; Kim, K. S. et al. Complete prevention of blood loss with self-sealing haemostatic needles. Nat. Mater. 2017, 16, 147-152.
Google Scholar
[16]
Hoffman, M. Remodeling the blood coagulation cascade. J. Thromb. Thrombolysis. 2003, 16, 17-20.
Google Scholar
[17]
Hickman, D. A.; Pawlowski, C. L.; Sekhon, U. D. S.; Marks, J.; Gupta, A. S. Biomaterials and advanced technologies for hemostatic management of bleeding. Adv. Mater. 2018, 30, 1700859.
Google Scholar
[18]
Eagle, H.; Harris, T. N. Studies in blood coagulation: V. The coagulation of blood by proteolytic enzymes (trypsin, papain). J. Gen. Physiol. 1937, 20, 543-560.
Google Scholar
[19]
Ferguson, J. H.; Wilson, E. G.; Iatridis, S. G.; Rierson, H. A.; Johnston, B. R. Enzymes and blood clotting. I. Trypsin as an accessory factor. J. Clin. Invest. 1960, 39, 1942-1952.
Google Scholar
[20]
Grunwald, P. Biocatalysis: Biochemical Fundamentals and Applications, 2nd ed.; World Scientific: New Jersey, 2017.
[21]
Achneck, H. E.; Sileshi, B.; Jamiolkowski, R. M.; Albala, D. M.; Shapiro, M. L.; Lawson, J. H. A comprehensive review of topical hemostatic agents: Efficacy and recommendations for use. Ann. Surg. 2010, 251, 217-228.
Google Scholar
[22]
Pourshahrestani, S.; Zeimaran, E.; Djordjevic, I.; Kadri, N. A.; Towler, M. R. Inorganic hemostats: The state-of-the-art and recent advances. Mater. Sci. Eng.: C 2016, 58, 1255-1268.
Google Scholar
[23]
Bennett, B. L.; Littlejohn, L. Review of new topical hemostatic dressings for combat casualty care. Mil. Med. 2014, 179, 497-514.
Google Scholar
[24]
Kheirabadi, B. S.; Mace, J. E.; Terrazas, I. B.; Fedyk, C. G.; Estep, J. S.; Dubick, M. A.; Blackbourne, L. H. Safety evaluation of new hemostatic agents, smectite granules, and kaolin-coated gauze in a vascular injury wound model in swine. J. Trauma. 2010, 68, 269-278.
Google Scholar
[25]
Huang, R. X.; Carney, R. P.; Ikuma, K.; Stellacci, F.; Lau, B. L. T. Effects of surface compositional and structural heterogeneity on nanoparticle-protein interactions: Different protein configurations. ACS Nano 2014, 8, 5402-5412.
Google Scholar
[26]
De, M.; You, C. C.; Srivastava, S.; Rotello, V. M. Biomimetic interactions of proteins with functionalized nanoparticles: A thermodynamic study. J. Am. Chem. Soc. 2007, 129, 10747-10753.
Google Scholar
[27]
Sandros, M. G.; Gao, D.; Gokdemir, C.; Benson, D. E. General, high-affinity approach for the synthesis of fluorophore appended protein nanoparticle assemblies. Chem. Commun. 2005, 2832-2834.
Google Scholar
[28]
Zhou, Y.; Liu, Z. Y.; Zhang, J. B.; Dou, T. Y.; Chen, J.; Ge, G. B.; Zhu, S. J.; Wang, F. J. Prediction of ligand modulation patterns on membrane receptors via lysine reactivity profiling. Chem. Commun. 2019, 55, 4311-4314.
Google Scholar
[29]
Liu, Z. Y.; Zhou, Y.; Liu, J.; Chen, J.; Heck, A. J. R.; Wang, F. J. Reductive methylation labeling, from quantitative to structural proteomics. TrAC Trends Anal. Chem. 2019, 118, 771-778.
Google Scholar
[30]
Zhou, Y.; Wu, Y.; Yao, M. D.; Liu, Z. Y.; Chen, J.; Chen, J.; Tian, L. R.; Han, G. Y.; Shen, J. R.; Wang, F. J. Probing the lysine proximal microenvironments within membrane protein complexes by active dimethyl labeling and mass spectrometry. Anal. Chem. 2016, 88, 12060-12065.
Google Scholar
[31]
Boersema, P. J.; Raijmakers, R.; Lemeer, S.; Mohammed, S.; Heck, A. J. R. Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics. Nat. Protoc. 2009, 4, 484-494.
Google Scholar
[32]
Lozano, R.; Naghavi, M.; Foreman, K.; Lim, S.; Shibuya, K.; Aboyans, V.; Abraham, J.; Adair, T.; Aggarwal, R.; Ahn, S. Y. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the global burden of disease study 2010. Lancet 2012, 380, 2095-2128.
Google Scholar
[33]
Butler, F. K. Jr.; Blackbourne, L. H. Battlefield trauma care then and now: A decade of tactical combat casualty care. J. Trauma Acute Care Surg. 2012, 73, S395-S402.
Google Scholar
[34]
Kauvar, D. S.; Lefering, R.; Wade, C. E. Impact of hemorrhage on trauma outcome: An overview of epidemiology, clinical presentations, and therapeutic considerations. J. Trauma 2006, 60, S3-S11.
Google Scholar
[35]
Cannon, J. W. Hemorrhagic shock. N. Engl. J. Med. 2018, 378, 370-379.
Google Scholar
[36]
Levy, J. H.; Goodnough, L. T. How I use fibrinogen replacement therapy in acquired bleeding. Blood 2015, 125, 1387-1393.
Google Scholar
[37]
Behrens, A. M.; Sikorski, M. J.; Kofinas, P. Hemostatic strategies for traumatic and surgical bleeding. J. Biomed. Mater. Res. 2014, 102, 4182-4194.
Google Scholar
[38]
Bertram, J. P.; Williams, C. A.; Robinson, R.; Segal, S. S.; Flynn, N. T.; Lavik, E. B. Intravenous hemostat: Nanotechnology to halt bleeding. Sci. Transl. Med. 2009, 1, 11ra22.
Google Scholar
[39]
Chan, L. W.; Wang, X.; Wei, H.; Pozzo, L. D.; White, N. J.; Pun, S. H. A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis. Sci. Transl. Med. 2015, 7, 277ra29.
Google Scholar
[40]
Gordy, S. D.; Rhee, P.; Schreiber, M. A. Military applications of novel hemostatic devices. Expert Rev. Med. Devic. 2011, 8, 41-47.
Google Scholar
[41]
Kheirabadi, B. Evaluation of topical hemostatic agents for combat wound treatment. US Army Med. Dep. J. 2011, 25-37.
Google Scholar
[42]
Chen, H.; Shang, X. Q.; Yu, L. S.; Xiao, L. P.; Fan, J. Safety evaluation of a low-heat producing zeolite granular hemostatic dressing in a rabbit femoral artery hemorrhage model. J. Biomater. Appl. 2020, 34, 988-997.
Google Scholar
[43]
Yu, L. S.; Shang, X. Q.; Chen, H.; Xiao, L. P.; Zhu, Y. H.; Fan, J. A tightly-bonded and flexible mesoporous zeolite-cotton hybrid hemostat. Nat. Commun. 2019, 10, 1932.
Google Scholar
[44]
Transue, T. R.; Krahn, J. M.; Gabel, S. A.; DeRose, E. F.; London, R. E. X-ray and NMR characterization of covalent complexes of trypsin, borate, and alcohols. Biochemistry 2004, 43, 2829-2839.
Google Scholar
[45]
Gabrieli, A.; Sant, M.; Demontis, P.; Suffritti, G. B. Development and optimization of a new force field for flexible aluminosilicates, enabling fast molecular dynamics simulations on parallel architectures. J. Phys. Chem. C. 2013, 117, 503-509.
Google Scholar
[46]
Huang, J.; Mackerell, A. D. Jr. CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data. J. Comput. Chem. 2013, 34, 2135-2145.
Google Scholar
Nano Research
Volume 14 Issue 9,
September 2021
Pages 3309-3318
DOI: 10.1007/s12274-021-3394-z
Cite this article:
Yu L, Yu B, Chen H, et al. Highly efficient artificial blood coagulation shortcut confined on Ca-zeolite surface. Nano Research, 2021, 14(9): 3309-3318. https://doi.org/10.1007/s12274-021-3394-z
Topics:
Bioactivity
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Received: 29 December 2020
Revised: 07 February 2021
Accepted: 08 February 2021
Published: 18 March 2021
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021
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