МЕТОДЫ И ИННОВАЦИОННЫЕ ПОДХОДЫ ДЛЯ ОСТАНОВКИ ОБШИРНОГО КРОВОТЕЧ ЕНИЯ

Неконтролируемое кровотечение может стать опасной для жизни травмой менее чем за пять минут. Целью данной работы является обзор перспективных технологий создания геля для остановки массивного кровотечения. Биополимеры - это природные соединения, которые включают в себя несколько полисахаридов и полипептидов. Благодаря своей особой молекулярной структуре и биологической активности они вызвали любопытство биомедицинских исследователей и продемонстрировали высокий потенциал для терапевтических изменений. Биополимеры продемонстрировали превосходную способность к биологическому разложению, надежную биосовместимость и неэкзотермическую реактивность при оказании первой помощи при гемостазе по сравнению с синтетическими полимерами и неорганическими кровоостанавливающими материалами. Учитывая растущую важность функционализации биополимеров, мы исследовали модификацию полимеров на основе их функциональных свойств, таких как биоадгезия, стимуляция заряда и включение функциональных групп и ионов-прокоагулянтов. Многочисленные исследования продемонстрировали превосходный гемостатический эффект, однако все еще необходимо дальнейшее изучение того, как различные виды материалов влияют на процесс гемостаза. Клиническая трансформация гемостатических материалов отстает от их фундаментальных исследований. В целом, материалы с небольшим количеством базовых компонентов лучше поддаются трансформации, но это увеличило необходимость тщательного планирования при их проектировании. Наконец, при проектировании следует уделять больше внимания молекулярным структурам и формам кровоостанавливающих материалов. Важно тщательно изучить, как компоненты взаимодействуют в процессе коагуляции. Ожидается, что соответствующие конструкции кровоостанавливающих материалов позволят быстро перейти от лабораторных разработок к постели пациента.

1. Ahmadian Z., Correia A., Hasany M., Figueiredo P., Dobakhti F., Eskandari M.R., Hosseini S.H., Abiri R., Khorshid S., Hirvonen J., Santos H.A., Shahbazi M.A., 2021. A Hydrogen-Bonded Extracellular Matrix-Mimicking Bactericidal Hydrogel with Radical Scavenging and Hemostatic Function for pH-Responsive Wound Healing Acceleration. Adv Healthc Mater 10. https://doi.org/10.1002/adhm.202001122.

2. An S., Jeon E.J., Jeon J., Cho S.W., 2019. A serotonin- modified hyaluronic acid hydrogel for multifunctional hemostatic adhesives inspired by a platelet coagulation mediator. Mater Horiz 6, 1169 – 1178. https://doi.org/10.1039/c9mh00157c.

3. Aydemir Sezer U., Sahin İ., Aru B., Olmez H., Yanıkkaya Demirel G., Sezer S., 2019. Cytotoxicity, bactericidal and hemostatic evaluation of oxidized cellulose microparticles: Structure and oxidation degree approach. Carbohydr Polym 219, 87 – 94. https://doi.org/10.1016/j.carbpol.2019.05.005.

4. Bal-Ozturk A., Cecen B., Avci-Adali M., Topkaya S.N., Alarcin E., Yasayan G., Li Y.C.E., Bulkurcuoglu B., Akpek A., Avci H., Shi K., Shin S.R., Hassan S., 2021a/b. Tissue adhesives: From research to clinical translation. Nano Today. https://doi.org/10.1016/j.nantod.2020.101049.

5. Che C., Liu L., Wang X., Zhang X., Luan S., Yin J., Li X., Shi H., 2020a/b. Surface-Adaptive and On-Demand Antibacterial Sponge for Synergistic Rapid Hemostasis and Wound Disinfection. ACS Biomater Sci Eng 6, 1776 – 1786. https://doi.org/10.1021/acsbiomaterials.0c00069.

6. Chen J., Qiu L., Li Q., Ai J., Liu H., Chen Q., 2021. Rapid hemostasis accompanied by antibacterial action of calcium crosslinking tannic acid-coated mesoporous silica/silver Janus nanoparticles. Materials Science and Engineering C 123. https://doi.org/10.1016/j.msec.2021.111958.

7. Bulger, E.M., Snyder, D., Schoelles, K., Gotschall, C., Dawson, D., Lang, E., Sanddal, N.D., Butler, F.K., Fallat, M., Taillac, P., White, L., Salomone, J.P., Seifarth, W., Betzner, M.J., Johannigman, J., McSwain, N., 2014. An evidence- based prehospital guideline for external hemorrhage control: American college of surgeons committee on trauma. Prehospital Emergency Care 18, 163–173. https://doi.org/10.3109/10903127.2014.896962.

8. Chen K., Pan H., Yan Z., Li Y., Ji D., Yun K., Su Y., Liu D., Pan W., 2021. A novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers for postoperative rapid hemostasis and prevention of tumor recurrence. Int J Biol Macromol 182, 1339 – 1350. https://doi.org/10.1016/j.ijbiomac.2021.05.074.

9. Chen Y., Wu L., Li P., Hao X., Yang X., Xi G., Liu W., Feng Y., He H., Shi C., 2020. Polysaccharide Based Hemostatic Strategy for Ultrarapid Hemostasis. Macromol Biosci. https://doi.org/10.1002/mabi.201900370.

10. Chen Z., Wu H., Wang H., Zaldivar-Silva D., Agüero L., Liu Y., Zhang Z., Yin Y., Qiu B., Zhao J., Lu X., Wang S., 2021. An injectable anti-microbial and adhesive hydrogel for the effective noncompressible visceral hemostasis and wound repair. Materials Science and Engineering C 129. https://doi.org/10.1016/j.msec.2021.112422.

11. Cheng F., Liu C., Wei X., Yan T., Li H., He J., Huang Y., 2017. Preparation and Characterization of 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO)-Oxidized Cellulose Nanocrystal/Alginate Biodegradable Composite Dressing for Hemostasis Applications. ACS Sustain Chem Eng 5, 3819 – 3828. https://doi.org/10.1021/acssuschemeng.6b02849.

12. Cheng J., Feng S., Han S., Zhang X., Chen Y., Zhou X., Wang R., Li X., Hu H., Zhang J., 2016. Facile Assembly of Cost-Effective and Locally Applicable or Injectable Nanohemostats for Hemorrhage Control. ACS Nano 10, 9957 – 9973. https://doi.org/10.1021/acsnano.6b04124.

13. Cheng J., Liu J., Li M., Liu Z., Wang X., Zhang L., Wang Z., 2021. Hydrogel-Based Biomaterials Engineered from Natural-Derived Polysaccharides and Proteins for Hemostasis and Wound Healing. Front Bioeng Biotechnol. https://doi.org/10.3389/fbioe.2021.780187.

14. de La Harpe K.M., Kondiah P.P.D., Choonara Y.E., Marimuthu T., du Toit L.C., Pillay V., 2019. The hemocompatibility of nanoparticles: A review of cell-nanoparticle interactions and hemostasis. Cells. https://doi.org/10.3390/cells8101209.

15. Deng Y., Chen J., Huang J., Yang X., Zhang X., Yuan S., Liao W., 2020. Preparation and characterization of cellulose/flaxseed gum composite hydrogel and its hemostatic and wound healing functions evaluation. Cellulose 27, 3971–3988. https://doi.org/10.1007/s10570-020-03055-3.

16. di Lena F., 2014. Hemostatic polymers: The concept, state of the art and perspectives. J Mater Chem B. https:// doi.org/10.1039/c3tb21739f.

17. Fernando I.P.S., Lee W.W., Han E.J., Ahn G., 2020. Alginate-based nanomaterials: Fabrication techniques, properties, and applications. Chemical Engineering Journal. https://doi.org/10.1016/j.cej.2019.123823.

18. Ghimire S., Sarkar P., Rigby K., Maan A., Mukherjee S., Crawford K.E., Mukhopadhyay K., 2021a/b. Polymeric materials for hemostatic wound healing. Pharmaceutics. https://doi.org/10.3390/pharmaceutics13122127.

19. Zheng C., Zeng Q., Pimpi S., Wu W., Han K., Dong K., Lu T., 2020. Research status and development potential of composite hemostatic materials. J Mater Chem B. https:// doi.org/10.1039/d0tb00906g.

20. Graça M.F.P., Miguel S.P., Cabral C.S.D., Correia I.J., 2020. Hyaluronic acid - Based wound dressings: A review. Carbohydr Polym. https://doi.org/10.1016/j.carbpol.2020.116364.

21. Granville-Chapman J., Jacobs N., Midwinter M.J., 2011. Pre-hospital haemostatic dressings: A systematic review. Injury. https://doi.org/10.1016/j.injury.2010.09.037.

22. Guo T., Li W., Wang J., Luo T., Lou D., Wang B., Hao S., 2018. Recombinant human hair keratin proteins for halting bleeding. Artif Cells Nanomed Biotechnol 46, 456 – 461. https://doi.org/10.1080/21691401.2018.1459633.

23. Guo Y., Wang Y., Zhao X., Li X., Wang Q., Zhong W., Mequanint K., Zhan R., Xing M., Luo G., 2021. Snake extract-laden hemostatic bioadhesive gel cross-linked by visible light, Sci. Adv.

24. Hamedi H., Moradi S., Hudson S.M., Tonelli A.E., 2018. Chitosan based hydrogels and their applications for drug delivery in wound dressings: A review. Carbohydr Polym. https://doi.org/10.1016/j.carbpol.2018.06.114.

25. Han K., Bai Q., Wu W., Sun N., Cui N., Lu T., 2021. Gelatin-based adhesive hydrogel with self-healing, hemostasis, and electrical conductivity. Int J Biol Macromol 183, 2142–2151. https://doi.org/10.1016/j.ijbiomac.2021.05.147.

26. He Q., Gong K., Ao Q., Ma T., Yan Y., Gong Y., Zhang X., 2013. Positive charge of chitosan retards blood coagulation on chitosan films. J Biomater Appl 27, 1032–1045. https://doi.org/10.1177/0885328211432487.

27. He X.Y., Sun A., Li T., Qian Y.J., Qian H., Ling Y.F., Zhang L.H., Liu Q.Y., Peng T., Qian Z., 2020. Mussel- inspired antimicrobial gelatin/chitosan tissue adhesive rapidly activated in situ by H2O2/ascorbic acid for infected wound closure. Carbohydr Polym 247. https://doi.org/10.1016/j.carbpol.2020.116692.

28. He Y., Wang J., Si Y., Wang X., Deng H., Sheng Z.G., Li Y., Liu J.L., Zhao J., 2021. A novel gene recombinant collagen hemostatic sponge with excellent biocompatibility and hemostatic effect. Int J Biol Macromol 178, 296–305. https://doi.org/10.1016/j.ijbiomac.2021.02.162.

29. Hickman D.S.A., Pawlowski C.L., Sekhon U.D.S., Marks J., Gupta A. sen, 2018. Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding. Advanced Materials. https://doi.org/10.1002/adma.201700859.

30. Zheng Y., Pan N., Liu Y., Ren X., 2021. Novel porous chitosan/N-halamine structure with efficient antibacterial and hemostatic properties. Carbohydr Polym 253. https://doi.org/10.1016/j.carbpol.2020.117205.

31. Huang X., Fu Q., Deng Y., Wang F., Xia B., Chen Z., Chen G., 2021. Surface roughness of silk fibroin/alginate microspheres for rapid hemostasis in vitro and in vivo. Carbohydr Polym 253. https://doi.org/10.1016/j.carbpol.2020.117256.

32. Kerris E.W.J., Hoptay C., Calderon T., Freishtat R.J., 2020. Platelets and platelet extracellular vesicles in hemostasis and sepsis. Journal of Investigative Medicine. https:// doi.org/10.1136/jim-2019-001195.

33. Khan M.A., Mujahid M., 2019. A review on recent advances in chitosan based composite for hemostatic dressings. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2018.11.045.

34. Kim S.D., Hong S.L., Kim M.J., Kim J.Y., Kim Y.W., Koo S.K., Cho K.S., 2018. Effectiveness of hemostatic gelatin sponge as a packing material after septoplasty: A prospective, randomized, multicenter study. Auris Nasus Larynx 45, 286–290. https://doi.org/10.1016/j.anl.2017.05.007.

35. Kumar V.A., Taylor N.L., Jalan A.A., Hwang L.K., Wang B.K., Hartgerink J.D., 2014. A nanostructured synthetic collagen mimic for hemostasis. Biomacromolecules 15, 1484–1490. https://doi.org/10.1021/bm500091e.

36. Lan G., Li Q., Lu F., Yu K., Lu B., Bao R., Dai F., 2020. Improvement of platelet aggregation and rapid induction of hemostasis in chitosan dressing using silver nanoparticles. Cellulose 27, 385–400. https://doi.org/10.1007/s10570-019-02795-1.

37. Li G., Quan K., Xu C.C., Deng B., Wang X., 2018. Synergy in thrombin-graphene sponge for improved hemostatic efficacy and facile utilization. Colloids Surf B Biointerfaces 161, 27–34. https://doi.org/10.1016/j.colsurfb.2017.10.021.

38. Ma Y., Yao J., Liu Q., Han T., Zhao J., Ma X., Tong Y., Jin G., Qu K., Li B., Xu F., 2020. Liquid Bandage Harvests Robust Adhesive, Hemostatic, and Antibacterial Performances as a First-Aid Tissue Adhesive. Adv Funct Mater 30. https://doi.org/10.1002/adfm.202001820.

39. Malik A., Rehman F.U., Shah K.U., Naz S.S., Qaisar S., 2021. Hemostatic strategies for uncontrolled bleeding: A comprehensive update. J Biomed Mater Res B Appl Biomater. https://doi.org/10.1002/jbm.b.34806.

40. Manon-Jensen T., Kjeld N.G., Karsdal M.A., 2016. Collagen-mediated hemostasis. Journal of Thrombosis and Haemostasis 14, 438–448. https://doi.org/10.1111/jth.13249.

41. Mizuno Y., Mizuta R., Hashizume M., Taguchi T., 2017. Enhanced sealing strength of a hydrophobically-modified Alaska pollock gelatin-based sealant. Biomater Sci 5, 982–989. https://doi.org/10.1039/c6bm00829a.

42. Muir V.G., Burdick J.A., 2021. Chemically Modified Biopolymers for the Formation of Biomedical Hydrogels. Chem Rev. https://doi.org/10.1021/acs.chemrev.0c00923.

43. Muthiah Pillai N.S., Eswar K., Amirthalingam S., Mony U., Kerala Varma P., Jayakumar R., 2019. Injectable Nano Whitlockite Incorporated Chitosan Hydrogel for Effective Hemostasis. ACS Appl Bio Mater 2, 865 – 873. https://doi.org/10.1021/acsabm.8b00710.

44. Nam S., Mooney D., 2021a/b. Polymeric Tissue Adhesives. Chem Rev. https://doi.org/10.1021/acs.chemrev.0c00798.

45. Pourshahrestani S., Kadri N.A., Zeimaran E., Towler M.R., 2019. Well-ordered mesoporous silica and bioactive glasses: Promise for improved hemostasis. Biomater Sci. https://doi.org/10.1039/c8bm01041b.

46. Pourshahrestani S., Zeimaran E., Kadri N.A., Mutlu N., Boccaccini A.R., 2020. Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing. Adv Healthc Mater. https://doi.org/10.1002/adhm.202000905.

47. Qiao Z., Lv X., He S., Bai S., Liu X., Hou L., He J., Tong D., Ruan R., Zhang J., Ding J., Yang H., 2021. A mussel-inspired supramolecular hydrogel with robust tissue anchor for rapid hemostasis of arterial and visceral bleedings. Bioact Mater 6, 2829 - 2840. https://doi.org/10.1016/j.bioactmat.2021.01.039.

48. Roberts I., Ageron F.X., 2022. The role of tranexamic acid in trauma - a life-saving drug with proven benefit. Nat Rev Dis Primers. https://doi.org/10.1038/s41572-022-00367-5.

49. Sang Y., Roest M., de Laat B., de Groot P.G., Huskens D., 2021. Interplay between platelets and coagulation. Blood Rev. https://doi.org/10.1016/j.blre.2020.100733.

50. Su H., Wei S., Chen F., Cui R., Liu C., 2019. Tranexamic acid-loaded starch hemostatic microspheres. RSC Adv 9, 6245 – 6253. https://doi.org/10.1039/c8ra06662k.

51. Sultan M.T., Hong H., Lee O.J., Ajiteru O., Lee Y.J., Lee J.S., Lee H., Kim S.H., Park C.H., 2022. Silk Fibroin-Based Biomaterials for Hemostatic Applications. Biomolecules. https://doi.org/10.3390/biom12050660.

52. Sun Z., Chen X., Ma X., Cui X., Yi Z., Li X., 2018. Cellulose/keratin-catechin nanocomposite hydrogel for wound hemostasis. J Mater Chem B 6, 6133 – 6141. https:// doi.org/10.1039/C8TB01109E.

53. Sung Y.K., Lee D.R., Chung D.J., 2021. Advances in the development of hemostatic biomaterials for medical application. Biomater Res. https://doi.org/10.1186/s40824-021-00239-1.

54. Taboada G.M., Yang K., Pereira M.J.N., Liu S.S., Hu Y., Karp J.M., Artzi N., Lee Y., 2020. Overcoming the translational barriers of tissue adhesives. Nat Rev Mater. https://doi.org/10.1038/s41578-019-0171-7.

55. Tang Q., Chen C., Jiang Y., Huang J., Liu Y., Nthumba P.M., Gu G., Wu X., Zhao Y., Ren J., 2020. Engineering an adhesive based on photosensitive polymer hydrogels and silver nanoparticles for wound healing. J Mater Chem B 8, 5756–5764. https://doi.org/10.1039/d0tb00726a.

56. Versteeg H.H., Heemskerk J.W.M., Levi M., Reitsma P.H., 2013. New Fundamentals in hemostasis. Physiol Rev. https://doi.org/10.1152/physrev.00016.2011.

57. Wang D., Li W., Wang Y., Yin H., Ding Y., Ji J., Wang B., Hao S., 2019. Fabrication of an expandable keratin sponge for improved hemostasis in a penetrating trauma. Colloids Surf B Biointerfaces 182. https://doi.org/10.1016/j.colsurfb.2019.110367.

58. Zhu T., Wu J., Zhao N., Cai C., Qian Z., Si F., Luo H., Guo J., Lai X., Shao L., Xu J., 2018. Superhydrophobic/Superhydrophilic Janus Fabrics Reducing Blood Loss. Adv Healthc Mater 7. https://doi.org/10.1002/adhm.201701086.

59. Wang Y., Li X., Zhang Z., Ding S., Jiang H., Li J., Shen J., Xia X., 2016. Simultaneous determination of nitroimidazoles, benzimidazoles, and chloramphenicol components in bovine milk by ultra-high performance liquid chromatography- tandem mass spectrometry. Food Chem 192, 280–287. https://doi.org/10.1016/j.foodchem.2015.07.033.

60. Wang Y., Zhao Y., Qiao L., Zou F., Xie Y., Zheng Y., Chao Y., Yang Y., He W., Yang S., 2021. Cellulose fibers-reinforced self-expanding porous composite with multiple hemostatic efficacy and shape adaptability for uncontrollable massive hemorrhage treatment. Bioact Mater 6, 2089–2104. https://doi.org/10.1016/j.bioactmat.2020.12.014.

61. Wei W., Liu J., Peng Z. bin Liang M., Wang Y.S., Wang X.Q., 2020. Gellable silk fibroin-polyethylene sponge for hemostasis. Artif Cells Nanomed Biotechnol 48, 28–36. https://doi.org/10.1080/21691401.2019.1699805.

62. Weisel J.W., Litvinov R.I., 2019. Red blood cells: the forgotten player in hemostasis and thrombosis. Journal of Thrombosis and Haemostasis. https://doi.org/10.1111/jth.14360.

63. Wu X., Tang Z., Liao X., Wang Z., Liu H., 2020. Fabrication of chitosan@calcium alginate microspheres with porous core and compact shell, and application as a quick traumatic hemostat. Carbohydr Polym 247. https:// doi.org/10.1016/j.carbpol.2020.116669.

64. Yan S., Han G., Wang Q., Zhang S., You R., Luo Z., Xu A., Li X., Li M., Zhang Q., Kaplan D.L., 2019. Directed assembly of robust and biocompatible silk fibroin/hyaluronic acid composite hydrogels. Compos B Eng 176. https://doi.org/10.1016/j.compositesb.2019.107204.

65. Yan S., Wang W., Li X., Ren J., Yun W., Zhang K., Li G., Yin J., 2018. Preparation of mussel-inspired injectable hydrogels based on dual-functionalized alginate with improved adhesive, self-healing, and mechanical properties. J Mater Chem B 6, 6377–6390. https://doi.org/10.1039/C8TB01928B.

66. Yang H., Song L., Zou Y., Sun D., Wang L., Yu Z., Guo J., 2021. Role of Hyaluronic Acids and Potential as Regenerative Biomaterials in Wound Healing. ACS Appl Bio Mater. https://doi.org/10.1021/acsabm.0c01364.

67. Yu Y., Li P., Zhu C., Ning N., Zhang S., Vancso G.J., 2019. Multifunctional and Recyclable Photothermally Responsive Cryogels as Efficient Platforms for Wound Healing. Adv Funct Mater 29. https://doi.org/10.1002/adfm.201904402.

68. Zhang S., Li J., Chen S., Zhang X., Ma J., He J., 2020. Oxidized cellulose-based hemostatic materials. Carbohydr Polym. https://doi.org/10.1016/j.carbpol.2019.115585.

69. Zhang X., Chen X., Hong H., Hu R., Liu J., Liu C., 2022. Decellularized extracellular matrix scaffolds: Recent trends and emerging strategies in tissue engineering. Bioact Mater. https://doi.org/10.1016/j.bioactmat.2021.09.014.

70. Zhao X., Liang Y., Guo B., Yin Z., Zhu D., Han Y., 2021. Injectable dry cryogels with excellent blood-sucking expansion and blood clotting to cease hemorrhage for lethal deep-wounds, coagulopathy and tissue regeneration. Chemical Engineering Journal 403. https://doi.org/10.1016/j.cej.2020.126329.