Antimicrobial hydrogels with controllable mechanical properties for biomedical application

Abstract

The antibacterial hydrogels can be widely used in the biomedical area owing to their excellent properties. The main limitation of antibacterial hydrogels is their poor mechanical strength. In this study, the novel hydrogels were fabricated with a mixture of silk fibroin (SF), chitosan (CH), agarose (AG), and silver nanoparticles (SNPs) via facile reaction condition without inorganic substances. The mechanical property of these fabricated hydrogels can be modulated by the concentration of SF or AG. The rheological studies demonstrated enhanced elasticity of CH-doped hydrogels. Because of the presence of CH and Ag in hydrogels, the antimicrobial property against gram-positive and gram-negative bacteria was exhibited. Cytocompatibility test proved the very low toxic nature of the hydrogels. In addition, these composite hydrogels have a smaller porosity, higher swelling ratio, and good compatibility, indicating their great potential for biomedical application.

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References

  1. 1.

    R. Xu, G. Luo, H. Xia, W. He, J. Zhao, B. Liu, J. Tan, J. Zhou, D. Liu, Y. Wang, Z. Yao, R. Zhan, S. Yang, and J. Wu: Novel bilayer wound dressing composed of silicone rubber with particular micropores enhanced wound re-epithelialization and contraction. Biomaterials 40, 1–11 (2015).

    Article  CAS  Google Scholar 

  2. 2.

    C. Gong, Q. Wu, Y. Wang, D. Zhang, F. Luo, X. Zhao, Y. Wei, and Z. Qian: A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials 34, 6377–6387 (2013).

    CAS  Article  Google Scholar 

  3. 3.

    X. Zhao, H. Wu, B. Guo, R. Dong, Y. Qiu, and P.X. Ma: Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing. Biomaterials 122, 34–47 (2017).

    CAS  Article  Google Scholar 

  4. 4.

    A.R. Unnithan, G. Gnanasekaran, Y. Sathishkumar, Y.S. Lee, and C.S. Kim: Electrospun antibacterial polyurethane-cellulose acetate-zein composite mats for wound dressing. Carbohydr. Polym. 102, 884–892 (2014).

    CAS  Article  Google Scholar 

  5. 5.

    S. MacNeil: Progress and opportunities for tissue-engineered skin. Nature 445, 874–880 (2007).

    CAS  Article  Google Scholar 

  6. 6.

    S. Duchi, C. Onofrillo, C.D. O’Connell, R. Blanchard, C. Augustine, A.F. Quigley, R.M.I. Kapsa, P. Pivonka, G. Wallace, C. Di Bella, and P.F.M. Choong: Handheld co-axial bioprinting: Application to in situ surgical cartilage repair. Sci. Rep. 7, 5837 (2017).

    Article  CAS  Google Scholar 

  7. 7.

    J.L. Drury and D.J. Mooney: Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials 24, 4337–4351 (2003).

    CAS  Article  Google Scholar 

  8. 8.

    G.P. Raeber, M.P. Lutolf, and J.A. Hubbell: Molecularly engineered PEG hydrogels: A novel model system for proteolytically mediated cell migration. Biophys. J. 89, 1374–1388 (2005).

    CAS  Article  Google Scholar 

  9. 9.

    B.K. Mann, A.S. Gobin, A.T. Tsai, R.H. Schmedlen, and J.L. West: Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: Synthetic ECM analogs for tissue engineering. Biomaterials 22, 3045–3051 (2001).

    CAS  Article  Google Scholar 

  10. 10.

    T. Ngoc Quyen, Y.K. Joung, E. Lih, and K.D. Park: In situ forming and rutin-releasing chitosan hydrogels as injectable dressings for dermal wound healing. Biomacromolecules 12, 2872–2880 (2011).

    Article  CAS  Google Scholar 

  11. 11.

    B. Balakrishnan, M. Mohanty, A.C. Fernandez, P.V. Mohanan, and A. Jayakrishnan: Evaluation of the effect of incorporation of dibutyryl cyclic adenosine monophosphate in an in situ-forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials 27, 1355–1361 (2006).

    CAS  Article  Google Scholar 

  12. 12.

    J.Z. Yang, Y.S. Zhang, K. Yue, and A. Khademhosseini: Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta Biomater. 57, 1–25 (2017).

    CAS  Article  Google Scholar 

  13. 13.

    W. Li, X. Li, W. Li, T. Wang, X. Li, S. Pan, and H. Deng: Nanofibrous mats layer-by-layer assembled via electrospun cellulose acetate and electrosprayed chitosan for cell culture. Eur. Polym. J. 48, 1846–1853 (2012).

    CAS  Article  Google Scholar 

  14. 14.

    S. Mohammed, G. Chouhan, O. Anuforom, M. Cooke, A. Walsh, P. Morgan-Warren, M. Jenkins, and F. de Cogan: Thermosensitive hydrogel as an in situ gelling antimicrobial ocular dressing. Mater. Sci. Eng., C 78, 203–209 (2017).

    CAS  Article  Google Scholar 

  15. 15.

    V. Normand, D.L. Lootens, E. Amici, K.P. Plucknett, and P. Aymard: New insight into agarose gel mechanical properties. Biomacromolecules 1, 730–738 (2000).

    CAS  Article  Google Scholar 

  16. 16.

    Y. Yuan, L. Wang, R.J. Mu, J.N. Gong, Y.Y. Wang, Y.Z. Li, J.Q. Ma, J. Pang, and C.H. Wu: Effects of konjac glucomannan on the structure, properties, and drug release characteristics of agarose hydrogels. Carbohydr. Polym. 190, 196–203 (2018).

    CAS  Article  Google Scholar 

  17. 17.

    H.M. Pauly, L.W. Place, T.L.H. Donahue, and M.J. Kipper: Mechanical properties and cell compatibility of agarose hydrogels containing proteoglycan mimetic graft copolymers. Biomacromolecules 18, 2220–2229 (2017).

    CAS  Article  Google Scholar 

  18. 18.

    N.R. Raia, B.P. Partlow, M. McGill, E.P. Kimmerling, C.E. Ghezzi, and D.L. Kaplan: Enzymatically crosslinked silk-hyaluronic acid hydrogels. Biomaterials 131, 58–67 (2017).

    CAS  Article  Google Scholar 

  19. 19.

    L. Tozzi, P.A. Laurent, C.A. Di Buduo, X. Mu, A. Massaro, R. Bretherton, W. Stoppel, D.L. Kaplan, and A. Balduini: Multi-channel silk sponge mimicking bone marrow vascular niche for platelet production. Biomaterials 178, 122–133 (2018).

    CAS  Article  Google Scholar 

  20. 20.

    P. Dubey, S. Kumar, V.K. Aswal, S. Ravindranathan, P.R. Rajamohanan, A. Prabhune, and A. Nisal: Silk fibroin-sophorolipid gelation: Deciphering the underlying mechanism. Biomacromolecules 17, 3318–3327 (2016).

    CAS  Article  Google Scholar 

  21. 21.

    R. Gharibi, H. Yeganeh, A. Rezapour-Lactoee, and Z.M. Hassan: Stimulation of wound healing by electroactive, antibacterial, and antioxidant polyurethane/siloxane dressing membranes: In vitro and in vivo evaluations. ACS Appl. Mater. Interfaces 7, 24296–24311 (2015).

    CAS  Article  Google Scholar 

  22. 22.

    W-Y. Chen, H-Y. Chang, J-K. Lu, Y-C. Huang, S.G. Harroun, Y-T. Tseng, Y-J. Li, C-C. Huang, and H-T. Chang: Self-assembly of antimicrobial peptides on gold nanodots: Against multidrug-resistant bacteria and wound-healing application. Adv. Funct. Mater. 25, 7189–7199 (2015).

    CAS  Article  Google Scholar 

  23. 23.

    M. Dash, F. Chiellini, R.M. Ottenbrite, and E. Chiellini: Chitosan-A versatile semi-synthetic polymer in biomedical applications. Prog. Polym. Sci. 36, 981–1014 (2011).

    CAS  Article  Google Scholar 

  24. 24.

    H. Ueno, T. Mori, and T. Fujinaga: Topical formulations and wound healing applications of chitosan. Adv. Drug Delivery Rev. 52, 105–115 (2001).

    CAS  Article  Google Scholar 

  25. 25.

    R.R. Klossner, H.A. Queen, A.J. Coughlin, and W.E. Krause: Correlation of chitosan’s rheological properties and its ability to electrospin. Biomacromolecules 9, 2947–2953 (2008).

    CAS  Article  Google Scholar 

  26. 26.

    J. Chedly, S. Soares, A. Montembault, Y. von Boxberg, M. Veron-Ravaille, C. Mouffle, M.N. Benassy, J. Taxi, L. David, and F. Nothias: Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration. Biomaterials 138, 91–107 (2017).

    CAS  Article  Google Scholar 

  27. 27.

    H. Pirvanescu, M. Balasoiu, M.E. Ciurea, A.T. Balasoiu, and R. Manescu: Wound infections with multi-drug resistant bacteria. Chirurgia 109, 73–79 (2014).

    CAS  Google Scholar 

  28. 28.

    D. Liang, Z. Lu, H. Yang, J. Gao, and R. Chen: Novel asymmetric wettable AgNPs/chitosan wound dressing: In vitro and in vivo evaluation. ACS Appl. Mater. Interfaces 8, 3958–3968 (2016).

    CAS  Article  Google Scholar 

  29. 29.

    Z. Lu, J. Gao, Q. He, J. Wu, D. Liang, H. Yang, and R. Chen: Enhanced antibacterial and wound healing activities of microporous chitosan-Ag/ZnO composite dressing. Carbohydr. Polym. 156, 460–469 (2017).

    CAS  Article  Google Scholar 

  30. 30.

    T. Jayaramudu, K. Varaprasad, G.M. Raghavendra, E.R. Sadiku, K. Mohana Raju, and J. Amalraj: Green synthesis of tea Ag nanocomposite hydrogels via mint leaf extraction for effective antibacterial activity. J. Biomater. Sci., Polym. Ed. 28, 1588–1602 (2017).

    CAS  Article  Google Scholar 

  31. 31.

    M. Ahamed, M.S. AlSalhi, and M.K.J. Siddiqui: Silver nanoparticle applications and human health. Clin. Chim. Acta 411, 1841–1848 (2010).

    CAS  Article  Google Scholar 

  32. 32.

    P. Matricardi, C. Di Meo, T. Coviello, W.E. Hennink, and F. Alhaique: Interpenetrating polymer networks polysaccharide hydrogels for drug delivery and tissue engineering. Adv. Drug Delivery Rev. 65, 1172–1187 (2013).

    CAS  Article  Google Scholar 

  33. 33.

    Z.H. Ayub, M. Arai, and K. Hirabayashi: Mechanism of the gelation of fibroin solution. Biosci., Biotechnol., Biochem. 57, 1910–1912 (1993).

    CAS  Article  Google Scholar 

  34. 34.

    T. Asakura, A. Kuzuhara, R. Tabeta, and H. Saito: Conformation characterization of bombyx mori silk fibroin in the solid state by high-frequency 13c cross polarization–magic angle spinning NMR, X-ray diffraction, and infrared spectroscopy. Macromolecules 18, 1841–1845 (1985).

    CAS  Article  Google Scholar 

  35. 35.

    J. Magoshi, Y. Magoshi, M.A. Becker, and S. Nakamura: Biospinning by bombyx mori silkworm. Abstr. Pap. 212, 53–CELL (1996).

    Google Scholar 

  36. 36.

    T. Hanawa, A. Watanabe, T. Tsuchiya, R. Ikoma, M. Hidaka, and M. Sugihara: New oral dosage form for elderly patients—preparation and characterization of silk fibroin gel. Chem. Pharm. Bull. 43, 284–288 (1995).

    CAS  Article  Google Scholar 

  37. 37.

    Y. Zhou, Q. Dong, H. Yang, X. Liu, X. Yin, Y. Tao, Z. Bai, and W. Xu: Photocrosslinked maleilated chitosan/methacrylated poly(vinyl alcohol) bicomponent nanofibrous scaffolds for use as potential wound dressings. Carbohydr. Polym. 168, 220–226 (2017).

    CAS  Article  Google Scholar 

  38. 38.

    Y.P. Singh, N. Bhardwaj, and B.B. Mandal: Potential of agarose/silk fibroin blended hydrogel for in vitro cartilage tissue engineering. ACS Appl. Mater. Interfaces 8, 21236–21249 (2016).

    CAS  Article  Google Scholar 

  39. 39.

    M.V. Priya, R.A. Kumar, A. Sivashanmugam, S.V. Nair, and R. Jayakumar: Injectable amorphous chitin-agarose composite hydrogels for biomedical applications. J. Funct. Biomater. 6, 849–862 (2015).

    CAS  Article  Google Scholar 

  40. 40.

    K.J. Le Goff, C. Gaillard, W. Helbert, C. Garnier, and T. Aubry: Rheological study of reinforcement of agarose hydrogels by cellulose nanowhiskers. Carbohydr. Polym. 116, 117–123 (2015).

    Article  CAS  Google Scholar 

  41. 41.

    L.Y. Zheng and J.A.F. Zhu: Study on antimicrobial activity of chitosan with different molecular weights. Carbohydr. Polym. 54, 527–530 (2003).

    CAS  Article  Google Scholar 

  42. 42.

    M. Rai, A. Yadav, and A. Gade: Silver nanoparticles as a new generation of antimicrobials. Biotechnol. Adv. 27, 76–83 (2009).

    CAS  Article  Google Scholar 

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Acknowledgments

The research was supported by the Hi-Tech Research and Development 863 Program of China Grant (No. 2013AA102507), Funds of China Agriculture Research System (No. CARS-18-ZJ0102), and Chongqing Research Program of Basic Research and Frontier Technology (No. cstc2017jcyjAX0087).

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Correspondence to Fang-Yin Dai.

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Chen, SH., Li, Z., Liu, ZL. et al. Antimicrobial hydrogels with controllable mechanical properties for biomedical application. Journal of Materials Research 34, 1911–1921 (2019). https://doi.org/10.1557/jmr.2019.77

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