journal article·2022-12Open access

Mussel-inspired hydrogel with injectable self-healing and antibacterial properties promotes wound healing in burn wound infection

Ao Sun, Danrong Hu, Xinye He, Xiao Ji, Tao Li, Xiawei Wei, Zhiyong Qian

NPG Asia Materials· Volume 14· Issue 1

Abstract

Abstract Burn wound infections cause serious problems for public health. More than 180,000 patients die from burns every year worldwide. In addition, the difficulty of healing wounds and wound infections caused by burns affects the mental health of patients. Therefore, it is very important to develop a wound dressing that can promote wound repair and exhibits good antibacterial effects. Here, we used oxidized konjac glucomannan (OKGM), γ-poly(glutamic acid) modified with dopamine and L-cysteine (γ-PGA-DA-Cys) and ε-polylysine (ε-PL) to produce an OKGM/γ-PGA-DA-Cys/ε-PL (OKPP) hydrogel. This hydrogel was produced by thiol-aldehyde addition and Schiff-base reactions and has the ability to be injected and self-heal. The results showed that the hydrogel exhibits good antibacterial effects on Pseudomonas aeruginosa and Staphylococcus aureus and has antioxidant effects in vitro. Moreover, the hydrogel also exhibits good adhesion. In a burn wound infection model, the hydrogel promoted wound healing and reduced the production of inflammation. These results proved that the hydrogel has clinical potential as a wound dressing for burn wound infection.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Antimicrobial agents and applications · Wound Healing and Treatments · Biopolymer Synthesis and Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (51)

Show source-provided references
1. Markiewicz-G. A. et al. Burn wound healing: clinical complications, medical care, treatment, and dressing types: the current state of knowledge for clinical practice. Int. J. Environ. Res. Public Health. 19, 1338 (2022).10.3390/ijerph19031338 ↗
2. Greenhalgh, D. G. Management of burns. N. Engl. J. Med. 380, 2349–2359 (2019).10.1056/NEJMra1807442 ↗
3. Pereira, R. F., Barrias, C. C., Granja, P. L. & Bartolo, P. J. Advanced biofabrication strategies for skin regeneration and repair. Nanomedicine 8, 603–621 (2013).10.2217/nnm.13.50 ↗
4. Rowan, M. P. et al. Burn wound healing and treatment: review and advancements. Crit. Care 19, 243 (2015).10.1186/s13054-015-0961-2 ↗
5. Stanojcic, M., Vinaik, R. & Jeschke, M. G. Status and challenges of predicting and diagnosing sepsis in burn patients. Surg. Infect. 19, 168–175 (2018).10.1089/sur.2017.288 ↗
6. MacNeil, S. Progress and opportunities for tissue-engineered skin. Nature 445, 874–880 (2007).10.1038/nature05664 ↗
7. Wang, Y. W. et al. Burn injury: challenges and advances in burn wound healing, infection, pain and scarring. Adv. Drug Deliv. Rev. 123, 3–17 (2018).10.1016/j.addr.2017.09.018 ↗
8. Atiyeh, B. S., Gunn, S. W. & Hayek, S. N. State of the art in burn treatment. World J. Surg. 29, 131–148 (2005).10.1007/s00268-004-1082-2 ↗
9. Weng, T. T. et al. 3D bioprinting for skin tissue engineering: Current status and perspectives. J. Tissue Eng. 12, 20417314211028574 (2021).10.1177/20417314211028574 ↗
10. Bay, C. et al. Comparison of skin substitutes for acute and chronic wound management. Semin. Plast. Surg. 35, 171–180 (2021).10.1055/s-0041-1731463 ↗
11. Mofazzal Jahromi, M. A. et al. Nanomedicine and advanced technologies for burns: preventing infection and facilitating wound healing. Adv. Drug Deliv. Rev. 123, 33–64 (2018).10.1016/j.addr.2017.08.001 ↗
12. Groeber, F., Holeiter, M., Hampel, M., Hinderer, S. & Schenke-Layland, K. Skin tissue engineering — in vivo and in vitro applications. Adv. Drug Deliv. Rev. 63, 352–366 (2011).10.1016/j.addr.2011.01.005 ↗
13. Zhou, W. J. et al. Quantum dots-hydrogel composites for biomedical applications. Chin. Chem. Lett. 33, 1245–1253 (2022).10.1016/j.cclet.2021.09.027 ↗
14. Wang, C. G. et al. Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics 9, 65–76 (2019).10.7150/thno.29766 ↗
15. Pan, P. P. et al. A fast on-demand preparation of injectable self-healing nanocomposite hydrogels for efficient osteoinduction. Chin. Chem. Lett. 32, 2159–2163 (2021).10.1016/j.cclet.2020.12.001 ↗
16. Cheng, L. et al. Injectable polypeptide-protein hydrogels for promoting infected wound healing. Adv. Funct. Mater. 30, 2001196 (2020).10.1002/adfm.202001196 ↗
17. Liang, Y., Li, Z., Huang, Y., Yu, R. & Guo, B. Dual-dynamic-bond cross-linked antibacterial adhesive hydrogel sealants with on-demand removability for post-wound-closure and infected wound healing. ACS Nano 15, 7078–7093 (2021).10.1021/acsnano.1c00204 ↗
18. Liu, Y., Yang, Y., Wang, C. & Zhao, X. Stimuli-responsive self-assembling peptides made from antibacterial peptides. Nanoscale 5, 6413–6421 (2013).10.1039/c3nr00225j ↗
19. Rahal, A. et al. Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed. Res. Int. 2014, 761264 (2014).10.1155/2014/761264 ↗
20. Dong, R., Zhao, X., Guo, B. & Ma, P. X. Self-healing conductive injectable hydrogels with antibacterial activity as cell delivery carrier for cardiac cell therapy. ACS Appl. Mater. Interfaces 8, 17138–17150 (2016).10.1021/acsami.6b04911 ↗
21. Tian, R. et al. Fabrication of self-healing hydrogels with on-demand antimicrobial activity and sustained biomolecule release for infected skin regeneration. ACS Appl. Mater. Interfaces 10, 17018–17027 (2018).10.1021/acsami.8b01740 ↗
22. Hong, Y., Gong, Y., Gao, C. & Shen, J. Collagen-coated polylactide microcarriers/chitosan hydrogel composite: Injectable scaffold for cartilage regeneration. J. Biomed. Mater. Res. Part A 85A, 628–637 (2008).10.1002/jbm.a.31603 ↗
23. Liu, P. et al. Ionic liquid functionalized non-releasing antibacterial hydrogel dressing coupled with electrical stimulation for the promotion of diabetic wound healing. Chem. Eng. J. 415, 129025 (2021).10.1016/j.cej.2021.129025 ↗
24. Yu, H. & Xiao, C. Synthesis and properties of novel hydrogels from oxidized konjac glucomannan crosslinked gelatin for in vitro drug delivery. Carbohydr. Polym. 72, 479–489 (2008).10.1016/j.carbpol.2007.09.023 ↗
25. Zhu, L., Chen, J., Mao, X. & Tang, S. A γ-PGA/KGM-based injectable hydrogel as immunoactive and antibacterial wound dressing for skin wound repair. Mater. Sci. Eng. C 129, 112374 (2021).10.1016/j.msec.2021.112374 ↗
26. Kanniyappan, H., Thangavel, P., Chakraborty, S., Arige, V. & Muthuvijayan, V. Design and evaluation of Konjac glucomannan-based bioactive interpenetrating network (IPN) scaffolds for engineering vascularized bone tissues. Int. J. Biol. Macromol. 143, 30–40 (2020).10.1016/j.ijbiomac.2019.12.012 ↗
27. Liang, Y., Zhao, X., Hu, T., Han, Y. & Guo, B. Mussel-inspired, antibacterial, conductive, antioxidant, injectable composite hydrogel wound dressing to promote the regeneration of infected skin. J. Colloid Interface Sci. 556, 514–528 (2019).10.1016/j.jcis.2019.08.083 ↗
28. Li, S. D. et al. Bioinspired double-dynamic-bond crosslinked bioadhesive enables post-wound closure care. Adv. Funct. Mater. 30, 2000130 (2020).10.1002/adfm.202000130 ↗
29. Zhou, C. C. et al. A photopolymerized antimicrobial hydrogel coating derived from epsilon-poly-l-lysine. Biomaterials 32, 2704–2712 (2011).10.1016/j.biomaterials.2010.12.040 ↗
30. Wang, R. et al. A biomimetic mussel-inspired ε-poly-l-lysine hydrogel with robust tissue-anchor and anti-infection capacity. Adv. Funct. Mater. 27, 1604894 (2017).10.1002/adfm.201604894 ↗
31. Xu, H.-L. et al. Thiolated γ-polyglutamic acid as a bioadhesive hydrogel-forming material: evaluation of gelation, bioadhesive properties and sustained release of KGF in the repair of injured corneas. Biomater. Sci. 7, 2582–2599 (2019).10.1039/C9BM00341J ↗
32. Buescher, J. M. & Margaritis, A. Microbial biosynthesis of polyglutamic acid biopolymer and applications in the biopharmaceutical, biomedical and food industries. Crit. Rev. Biotechnol. 27, 1–19 (2007).10.1080/07388550601166458 ↗
33. Tong, Z. R. et al. In situ synthesis of poly (γ- glutamic acid)/alginate/AgNP composite microspheres with antibacterial and hemostatic properties. Carbohydr. Polym. 221, 21–28 (2019).10.1016/j.carbpol.2019.05.035 ↗
34. Yang, R. et al. Bioinspired poly (γ-glutamic acid) hydrogels for enhanced chondrogenesis of bone marrow-derived mesenchymal stem cells. Int. J. Biol. Macromol. 142, 332–344 (2020).10.1016/j.ijbiomac.2019.09.104 ↗
35. Weng, Y., Cao, Y., Arevalo, C., Vacanti, M. P. & Vacanti, C. A. Tissue-engineered composites of bone and cartilage for mandible condylar reconstruction. J. Oral. Maxillofac. Surg. 59, 185–190 (2001).10.1053/joms.2001.20491 ↗
36. Mirończuk-Chodakowska, I., Witkowska, A. M. & Zujko, M. E. Endogenous non-enzymatic antioxidants in the human body. Adv. Med. Sci. 63, 68–78 (2018).10.1016/j.advms.2017.05.005 ↗
37. Ulrich, K. & Jakob, U. The role of thiols in antioxidant systems. Free Radic. Biol. Med. 140, 14–27 (2019).10.1016/j.freeradbiomed.2019.05.035 ↗
38. Bernkop-Schnürch, A., Schwarz, V. & Steininger, S. Polymers with thiol groups: a new generation of mucoadhesive polymers? Pharm. Res. 16, 876–881 (1999).10.1023/A:1018830204170 ↗
39. Wang, L., Li, Y., Lin, L., Mu, R. & Pang, J. Novel synthesis of mussel inspired and Fe3+ induced pH-sensitive hydrogels: Adhesion, injectable, shapeable, temperature properties, release behavior and rheological characterization. Carbohydr. Polym. 236, 116045 (2020).10.1016/j.carbpol.2020.116045 ↗
40. He, X. Y. et al. Mussel-inspired antimicrobial gelatin/chitosan tissue adhesive rapidly activated in situ by H2O2/ascorbic acid for infected wound closure. Carbohydr. Polym. 247, 116692 (2020).10.1016/j.carbpol.2020.116692 ↗
41. Han, L. et al. Mussel-inspired adhesive and tough hydrogel based on nanoclay confined dopamine polymerization. ACS Nano 11, 2561–2574 (2017).10.1021/acsnano.6b05318 ↗
42. Liao, M. H. et al. Wearable, healable, and adhesive epidermal sensors assembled from mussel-inspired conductive hybrid hydrogel framework. Adv. Funct. Mater. 27, 1703852 (2017).10.1002/adfm.201703852 ↗
43. Fan, C., Fu, J., Zhu, W. & Wang, D.-A. A mussel-inspired double-crosslinked tissue adhesive intended for internal medical use. Acta Biomater. 33, 51–63 (2016).10.1016/j.actbio.2016.02.003 ↗
44. Chen, H. L. et al. An injectable self-healing hydrogel with adhesive and antibacterial properties effectively promotes wound healing. Carbohydr. Polym. 201, 522–531 (2018).10.1016/j.carbpol.2018.08.090 ↗
45. Yang, R. et al. Injectable adaptive self-healing hyaluronic acid/poly (γ-glutamic acid) hydrogel for cutaneous wound healing. Acta Biomater. 127, 102–115 (2021).10.1016/j.actbio.2021.03.057 ↗
46. Gharibi, R., Yeganeh, H., Rezapour-Lactoee, A. & Hassan, Z. M. 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).10.1021/acsami.5b08376 ↗
47. Zhang, D.-Y. et al. Multi-enzyme mimetic ultrasmall iridium nanozymes as reactive oxygen/nitrogen species scavengers for acute kidney injury management. Biomaterials 271, 120706 (2021).10.1016/j.biomaterials.2021.120706 ↗
48. Zhu, Q. Y. et al. Enhanced healing activity of burn wound infection by a dextran-HA hydrogel enriched with sanguinarine. Biomater. Sci. 6, 2472–2486 (2018).10.1039/C8BM00478A ↗
49. Huang, H. et al. Injectable hydrogel for postoperative synergistic photothermal-chemodynamic tumor and anti-infection therapy. Biomaterials 280, 121289 (2022).10.1016/j.biomaterials.2021.121289 ↗
50. Church, D., Elsayed, S., Reid, O., Winston, B. & Lindsay, R. Burn wound infections. Clin. Microbiol. Rev. 19, 403–434 (2006).10.1128/CMR.19.2.403-434.2006 ↗
51. Zheng, Y. Y. et al. Injectable supramolecular gelatin hydrogel loading of resveratrol and histatin-1 for burn wound therapy. Biomater. Sci. 8, 4810–4820 (2020).10.1039/D0BM00391C ↗