Please wait a minute...
Frontiers of Materials Science

ISSN 2095-025X

ISSN 2095-0268(Online)

CN 11-5985/TB

Postal Subscription Code 80-974

2018 Impact Factor: 1.701

Front. Mater. Sci.    2023, Vol. 17 Issue (4) : 230660    https://doi.org/10.1007/s11706-023-0660-x
RESEARCH ARTICLE
A nonmulberry silk fibroin-based robust mandruka for rapid hemostasis treatment
Hao Zhang1, Siyuan Luo1, Weili Yang1, Qisheng Luo1, Perumal Ramesh Kannan1, Yao Li1,2(), Xiangdong Kong1,2()
1. Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China
2. Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China
 Download: PDF(5755 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
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.

Keywords nonmulberry silk fibroin      Dictyoploca japonica      regenerated silk fibroin      hemostatic sponge     
Corresponding Author(s): Yao Li,Xiangdong Kong   
About author: Peng Lei and Charity Ngina Mwangi contributed equally to this work.
Issue Date: 20 October 2023
 Cite this article:   
Hao Zhang,Siyuan Luo,Weili Yang, et al. A nonmulberry silk fibroin-based robust mandruka for rapid hemostasis treatment[J]. Front. Mater. Sci., 2023, 17(4): 230660.
 URL:  
https://academic.hep.com.cn/foms/EN/10.1007/s11706-023-0660-x
https://academic.hep.com.cn/foms/EN/Y2023/V17/I4/230660
Fig.1  The preparation of DSF. (A) The photograph of the silkworm cocoon, the Dictyoploca japonica (upper) and Mulberry (below), and SEM images of the cocoon with different degumming conditions. Different concentrations (upper) and different time (below). (B) The photograph of the silk after degumming, the Dictyoploca japonica (upper) and Mulberry (below), and the SF solution extraction procedure uses different solvent systems (n = 3). (C) SEM images of DSF and SF after dissolving in LiSCN. The inserted photograph shows the solubility of DSF (left) and SF (right).
Fig.2  (A) Schematic illustration for the preparation of SF-based sponge. (B) SEM images of LiSCN-treated DSF (left), LiSCN-treated SF (middle), and CaCl2-treated SF (right). (C) XRD patterns of DSF and SF treated with LiSCN and CaCl2 solvent systems. (D) FTIR spectra of DSF as well as SFs treated with LiSCN and CaCl2 solvent systems, respectively. (E) Conformational analyses of sponges by FTIR spectroscopy.
Fig.3  Photographic images of DSF-based sponge. Representative SEM images show the microtopography of various formulations of SF-based sponge after lyophilization. The right side images show the magnified views.
Fig.4  DSF-based sponge for hemostasis. (A) Moisture absorption performance of SF-based hemostatic sponge and (B) the relative PBS absorption rate. (C) Clotting photographs of DSF–CMCS–GA after contact with blood for 1, 2, 3, and 4 min. (D) The quantitative blood absorption rate (n = 3). (E) Coagulation effect of DSF–CMCS–GA sponge after incubating with rabbit blood using filter-paper method.
Fig.5  Blood compatibility assay. (A) The BCI evaluation of DSF?CMCS?GA. (B) Hemolytic test of DSF?CMCS?GA. The inserted photograph shows the hemolysis performance. DI water was used as the positive control and PBS was the negative control (n = 3).
1 P Y, Yu W Zhong . Hemostatic materials in wound care.Burns and Trauma, 2021, 9: tkab019
https://doi.org/10.1093/burnst/tkab019
2 D J Dries . 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
https://doi.org/10.1186/1757-7241-18-63
3 M A, Khan M Mujahid . A review on recent advances in chitosan based composite for hemostatic dressings.International Journal of Biological Macromolecules, 2019, 124: 138–147
https://doi.org/10.1016/j.ijbiomac.2018.11.045
4 D A, Hickman C L, Pawlowski U D S, Sekhon et al.. Biomaterials and advanced technologies for hemostatic management of bleeding.Advanced Materials, 2018, 30(4): 1700859
https://doi.org/10.1002/adma.201700859
5 L H, Blackbourne D G, Baer B J, Eastridge et al.. Military medical revolution: prehospital combat casualty care.Journal of Trauma and Acute Care Surgery, 2012, 73(6): S372–S377
https://doi.org/10.1097/TA.0b013e3182755662
6 R, Mabry J G Mcmanus . Prehospital advances in the management of severe penetrating trauma.Critical Care Medicine, 2008, 36(7 Suppl): S258–S266
https://doi.org/10.1097/CCM.0b013e31817da674
7 C Y, Zou Q J, Li J J, Hu et al.. Design of biopolymer-based hemostatic material: starting from molecular structures and forms.Materials Today Bio, 2022, 17: 100468
https://doi.org/10.1016/j.mtbio.2022.100468
8 A, Malik F U, Rehman K U, Shah et al.. Hemostatic strategies for uncontrolled bleeding: a comprehensive update.Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2021, 109(10): 1465–1477
https://doi.org/10.1002/jbm.b.34806
9 Y, Guo M, Wang Q, Liu et al.. Recent advances in the medical applications of hemostatic materials.Theranostics, 2023, 13(1): 161–196
https://doi.org/10.7150/thno.79639
10 L Y, Wang X R, You C L, Dai et al.. Hemostatic nanotechnologies for external and internal hemorrhage management.Biomaterials Science, 2020, 8(16): 4396–4412
https://doi.org/10.1039/D0BM00781A
11 D N, Rockwood R C, Preda T, Yücel et al.. Materials fabrication from bombyx mori silk fibroin.Nature Protocols, 2011, 6(10): 1612–1631
https://doi.org/10.1038/nprot.2011.379
12 A, Mushtaq H, Zhang M Y, Cui et al.. 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
https://doi.org/10.1016/j.colsurfa.2022.130513
13 T T, Cui J F, Yu Q, Li et al.. 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
https://doi.org/10.1002/adma.202000982
14 X, Yao S Z, Zou S N, Fan et al.. Bioinspired silk fibroin materials: from silk building blocks extraction and reconstruction to advanced biomedical applications.Materials Today Bio, 2022, 16: 100381
https://doi.org/10.1016/j.mtbio.2022.100381
15 Z W, Qiao X L, Lv S H, He et al.. A mussel-inspired supramolecular hydrogel with robust tissue anchor for rapid hemostasis of arterial and visceral bleedings.Bioactive Materials, 2021, 6(9): 2829–2840
https://doi.org/10.1016/j.bioactmat.2021.01.039
16 D D, Luo C X, Yao R, Zhang et al.. 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
https://doi.org/10.1021/acsbiomaterials.1c01060
17 M N, Dai M, Li J J, Gong et al.. Silk fibroin/gelatin/calcium alginate composite materials: preparation, pore characteristics, comprehensive hemostasis in vitro.Materials & Design, 2022, 216: 110577
https://doi.org/10.1016/j.matdes.2022.110577
18 J, Lee H N, Choi H J, Cha et al.. 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
https://doi.org/10.1021/acs.biomac.2c01512
19 S, Biswas B K, Bhunia G, Janani et al.. Silk fibroin based formulations as potential hemostatic agents.ACS Biomaterials Science & Engineering, 2022, 8(6): 2654–2663
https://doi.org/10.1021/acsbiomaterials.2c00170
20 S, Mehrotra Melo B A G, de M, Hirano et al.. Nonmulberry silk based ink for fabricating mechanically robust cardiac patches and endothelialized myocardium-on-a-chip application.Advanced Functional Materials, 2020, 30(12): 1907436
https://doi.org/10.1002/adfm.201907436
21 S, Sapru S, Das M, Mandal et al.. Prospects of nonmulberry silk protein sericin-based nanofibrous matrices for wound healing — in vitro and in vivo investigations.Acta Biomaterialia, 2018, 78: 137–150
https://doi.org/10.1016/j.actbio.2018.07.047
22 D, Naskar A K, Ghosh M, Mandal et al.. 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
https://doi.org/10.1016/j.biomaterials.2017.05.014
23 N, Sahu P, Baligar S, Midha et al.. Nonmulberry silk fibroin scaffold shows superior osteoconductivity than mulberry silk fibroin in calvarial bone regeneration.Advanced Healthcare Materials, 2015, 4(11): 1709–1721
https://doi.org/10.1002/adhm.201500283
24 S Z, Zou X, Yao H L, Shao et al.. Nonmulberry silk fibroin-based biomaterials: impact on cell behavior regulation and tissue regeneration.Acta Biomaterialia, 2022, 153: 68–84
https://doi.org/10.1016/j.actbio.2022.09.021
25 S, Mehrotra S K, Nandi B B Mandal . 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
https://doi.org/10.1039/C7TB01494E
26 S Z, Zou X R, Wang S N, Fan et al.. Fabrication and characterization of regenerated antheraea pernyi silk fibroin scaffolds for schwann cell culturing.European Polymer Journal, 2019, 117: 123–133
https://doi.org/10.1016/j.eurpolymj.2019.04.056
27 G Q, Fang S, Sapru S, Behera et al.. 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
https://doi.org/10.1039/C6TB01049K
28 C Z, Zhou F, Confalonieri N, Medina et al.. Fine organization of bombyx mori fibroin heavy chain gene.Nucleic Acids Research, 2000, 28(12): 2413–2419
https://doi.org/10.1093/nar/28.12.2413
29 C, Holland K, Numata J, Rnjak-Kovacina et al.. The biomedical use of silk: past, present, future.Advanced Healthcare Materials, 2019, 8(1): 1800465
https://doi.org/10.1002/adhm.201800465
30 C, Vepari D L Kaplan . Silk as a biomaterial.Progress in Polymer Science, 2007, 32(8‒9): 991–1007
https://doi.org/10.1016/j.progpolymsci.2007.05.013
31 Boni B O, Ode B M, Bakadia A R, Osi et al.. Immune response to silk sericin‒fibroin composites: potential immunogenic elements and alternatives for immunomodulation.Macromolecular Bioscience, 2022, 22(1): 2100292
https://doi.org/10.1002/mabi.202100292
32 H Y, Wang Z G, Wei Y Q Zhang . 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
https://doi.org/10.1016/j.ijbiomac.2019.12.066
33 X Y, Bian C Y, Cui Y, Qi et al.. Amino acid surfactant-induced superfast gelation of silk fibroin for treating noncompressible hemorrhage.Advanced Functional Materials, 2022, 32(44): 2207349
https://doi.org/10.1002/adfm.202207349
34 Y B, Zhang H J, Wang A, Raza et al.. Preparation and evaluation of chitosan/polyvinylpyrrolidone/zein composite hemostatic sponges.International Journal of Biological Macromolecules, 2022, 205: 110–117
https://doi.org/10.1016/j.ijbiomac.2022.02.013
35 Y Q Zhang . Applications of natural silk protein sericin in biomaterials.Biotechnology Advances, 2002, 20(2): 91–100
https://doi.org/10.1016/S0734-9750(02)00003-4
36 L H, Fan H, Yang J, Yang et al.. Preparation and characterization of chitosan/gelatin/PVA hydrogel for wound dressings.Carbohydrate Polymers, 2016, 146: 427–434
https://doi.org/10.1016/j.carbpol.2016.03.002
[1] FMS-23660-OF-Zh_suppl_1 Download
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed