A nonmulberry silk fibroin-based robust mandruka for rapid hemostasis treatment

Abstract

Uncontrolled hemorrhage resulting from traumas causes severe health risks. There is an urgent need for expeditious hemostatic materials to treat bleeding incidents. Here, we developed a natural protein-based hemostatic sponge extracted from nonmulberry cocoons that exhibited rapid coagulation and effective absorption. We first built a degumming and dissolution system suitable for the Dictyoploca japonica cocoons to obtain regenerated silk fibroin (DSF). The DSF was then combined with carboxymethyl chitosan (CMCS) by glutaraldehyde (GA) crosslinking to ensure the structural stability of sponges. The resulting DSF–CMCS–GA exhibited remarkable hemostatic properties, displaying the highest absorption rate. It also demonstrated comparable efficacy to commercial hemostatic sponges. The blood-clotting index and hemolysis test showed that the prepared sponge possessed hemostatic activity and good hemocompatibility. Compared with mulberry silk fibroin hemostatic sponges (SF–CMCS–GA), DSF–CMCS–GA showed slightly better effects, making them a potential alternative to mulberry silk. In conclusion, our study introduces the use of Dictyoploca japonica silk fibroin for hemostasis, highlighting the exploitation of wild silkworm resources and providing an excellent silk fibroin-based hemostatic sealant for acute accident wounds and biomedical applications involving massive hemorrhage.

Graphical abstract

Keywords

nonmulberry silk fibroin / Dictyoploca japonica / regenerated silk fibroin / hemostatic sponge

References

[1] Yu P Y, Zhong W . Hemostatic materials in wound care.Burns and Trauma, 2021, 9: tkab019

[2] Dries D J . The contemporary role of blood products and components used in trauma resuscitation.Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 2010, 18(1): 63–80

[3] Khan M A, Mujahid M . A review on recent advances in chitosan based composite for hemostatic dressings.International Journal of Biological Macromolecules, 2019, 124: 138–147

[4] Hickman D A, Pawlowski C L, Sekhon U D S, . Biomaterials and advanced technologies for hemostatic management of bleeding.Advanced Materials, 2018, 30(4): 1700859

[5] Blackbourne L H, Baer D G, Eastridge B J, . Military medical revolution: prehospital combat casualty care.Journal of Trauma and Acute Care Surgery, 2012, 73(6): S372–S377

[6] Mabry R, Mcmanus J G . Prehospital advances in the management of severe penetrating trauma.Critical Care Medicine, 2008, 36(7 Suppl): S258–S266

[7] Zou C Y, Li Q J, Hu J J, . Design of biopolymer-based hemostatic material: starting from molecular structures and forms.Materials Today Bio, 2022, 17: 100468

[8] Malik A, Rehman F U, Shah K U, . Hemostatic strategies for uncontrolled bleeding: a comprehensive update.Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2021, 109(10): 1465–1477

[9] Guo Y, Wang M, Liu Q, . Recent advances in the medical applications of hemostatic materials.Theranostics, 2023, 13(1): 161–196

[10] Wang L Y, You X R, Dai C L, . Hemostatic nanotechnologies for external and internal hemorrhage management.Biomaterials Science, 2020, 8(16): 4396–4412

[11] Rockwood D N, Preda R C, Yücel T, . Materials fabrication from bombyx mori silk fibroin.Nature Protocols, 2011, 6(10): 1612–1631

[12] Mushtaq A, Zhang H, Cui M Y, . ROS-responsive chlorin e6 and silk fibroin loaded ultrathin magnetic hydroxyapatite nanorods for T₁-magnetic resonance imaging guided photodynamic therapy in vitro.Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2023, 656(Part B): 130513

[13] Cui T T, Yu J F, Li Q, . Large-scale fabrication of robust artificial skins from a biodegradable sealant-loaded nanofiber scaffold to skin tissue via microfluidic blow-spinning.Advanced Materials, 2020, 32(32): 2000982

[14] Yao X, Zou S Z, Fan S N, . Bioinspired silk fibroin materials: from silk building blocks extraction and reconstruction to advanced biomedical applications.Materials Today Bio, 2022, 16: 100381

[15] Qiao Z W, Lv X L, He S H, . A mussel-inspired supramolecular hydrogel with robust tissue anchor for rapid hemostasis of arterial and visceral bleedings.Bioactive Materials, 2021, 6(9): 2829–2840

[16] Luo D D, Yao C X, Zhang R, . Silk fibroin/collagen blended membrane fabricated via a green papermaking method for potential guided bone regeneration application: in vitro and in vivo evaluation.ACS Biomaterials Science & Engineering, 2021, 7(12): 5788–5797

[17] Dai M N, Li M, Gong J J, . Silk fibroin/gelatin/calcium alginate composite materials: preparation, pore characteristics, comprehensive hemostasis in vitro.Materials & Design, 2022, 216: 110577

[18] Lee J, Choi H N, Cha H J, . Microporous hemostatic sponge based on silk fibroin and starch with increased structural retentivity for contact activation of the coagulation cascade.Biomacromolecules, 2023, 24(4): 1763–1773

[19] Biswas S, Bhunia B K, Janani G, . Silk fibroin based formulations as potential hemostatic agents.ACS Biomaterials Science & Engineering, 2022, 8(6): 2654–2663

[20] Mehrotra S, de Melo B A G, Hirano M, . Nonmulberry silk based ink for fabricating mechanically robust cardiac patches and endothelialized myocardium-on-a-chip application.Advanced Functional Materials, 2020, 30(12): 1907436

[21] Sapru S, Das S, Mandal M, . Prospects of nonmulberry silk protein sericin-based nanofibrous matrices for wound healing — in vitro and in vivo investigations.Acta Biomaterialia, 2018, 78: 137–150

[22] Naskar D, Ghosh A K, Mandal M, . Dual growth factor loaded nonmulberry silk fibroin/carbon nanofiber composite 3D scaffolds for in vitro and in vivo bone regeneration.Biomaterials, 2017, 136: 67–85

[23] Sahu N, Baligar P, Midha S, . Nonmulberry silk fibroin scaffold shows superior osteoconductivity than mulberry silk fibroin in calvarial bone regeneration.Advanced Healthcare Materials, 2015, 4(11): 1709–1721

[24] Zou S Z, Yao X, Shao H L, . Nonmulberry silk fibroin-based biomaterials: impact on cell behavior regulation and tissue regeneration.Acta Biomaterialia, 2022, 153: 68–84

[25] Mehrotra S, Nandi S K, Mandal B B . Stacked silk‒cell monolayers as a biomimetic three dimensional construct for cardiac tissue reconstruction.Journal of Materials Chemistry B: Materials for Biology and Medicine, 2017, 5(31): 6325–6338

[26] Zou S Z, Wang X R, Fan S N, . Fabrication and characterization of regenerated antheraea pernyi silk fibroin scaffolds for schwann cell culturing.European Polymer Journal, 2019, 117: 123–133

[27] Fang G Q, Sapru S, Behera S, . Exploration of the tight structural‒mechanical relationship in mulberry and non-mulberry silkworm silks.Journal of Materials Chemistry B: Materials for Biology and Medicine, 2016, 4(24): 4337–4347

[28] Zhou C Z, Confalonieri F, Medina N, . Fine organization of bombyx mori fibroin heavy chain gene.Nucleic Acids Research, 2000, 28(12): 2413–2419

[29] Holland C, Numata K, Rnjak-Kovacina J, . The biomedical use of silk: past, present, future.Advanced Healthcare Materials, 2019, 8(1): 1800465

[30] Vepari C, Kaplan D L . Silk as a biomaterial.Progress in Polymer Science, 2007, 32(8‒9): 991–1007

[31] Ode Boni B O, Bakadia B M, Osi A R, . Immune response to silk sericin‒fibroin composites: potential immunogenic elements and alternatives for immunomodulation.Macromolecular Bioscience, 2022, 22(1): 2100292

[32] Wang H Y, Wei Z G, Zhang Y Q . Dissolution and regeneration of silk from silkworm bombyx mori in ionic liquids and its application to medical biomaterials.International Journal of Biological Macromolecules, 2020, 143: 594–601

[33] Bian X Y, Cui C Y, Qi Y, . Amino acid surfactant-induced superfast gelation of silk fibroin for treating noncompressible hemorrhage.Advanced Functional Materials, 2022, 32(44): 2207349

[34] Zhang Y B, Wang H J, Raza A, . Preparation and evaluation of chitosan/polyvinylpyrrolidone/zein composite hemostatic sponges.International Journal of Biological Macromolecules, 2022, 205: 110–117

[35] Zhang Y Q . Applications of natural silk protein sericin in biomaterials.Biotechnology Advances, 2002, 20(2): 91–100

[36] Fan L H, Yang H, Yang J, . Preparation and characterization of chitosan/gelatin/PVA hydrogel for wound dressings.Carbohydrate Polymers, 2016, 146: 427–434

Authors’ contributions

H.Z., S.L., Y.L. and X.K. designed the research. H.Z., S.L., W.Y., Y.L. and X.K. performed the research. All authors analyzed and interpreted the data. Y.L., H.Z., P.R.K. and X.K. wrote and revised the paper.

Declaration of competing interests

The authors declare that they have no competing interests.

Acknowledgements

This research was financially supported by the National Natural Science Foundation of China (Grant Nos. 51672250, 32301177, and 51902289), the Key Research & Development Program of Zhejiang Province (Grant Nos. 2021C01180 and 2019C04020), and the Scientific Research Foundation of Zhejiang Sci-Tech University (Grant No. 22212238-Y).

Electronic supplementary information

Supplementary materials can be found in the online version at https://doi.org/10.1007/s11706-023-0660-x and https://journal.hep.com.cn/foms/EN/10.1007/s11706-023-0660-x, which include Figs. S1‒S4 and Table S1.

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2023 Higher Education Press