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A novel hydrogel containing 4-methylcatechol for skin regeneration: in vitro and in vivo study

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Abstract

Skin damages are usual physical injuries and different studies have been done to improve wound healing. Hydrogel due to its properties like a moist environment and cooling wound site is a good option for wound treatment. In this study, we evaluated the consequence of using alginate/chitosan hydrogel contained various dosages of 4-Methylcatechol (0, 0.1, 1% (W/W)) on wound healing. After hydrogel fabrication, different tests like SEM, swelling, release, weight loss, and hemo- and cytocompatibility were done to characterize fabricated hydrogels. Finally, the rat model was used to assess Alginate/Chitosan hydrogel's therapeutic function containing 0.1 and 1% of 4-Methylcatechol. The pore size of hydrogel was between 24.5 ± 9 and 62.1 ± 11.63 µm and about 90% of hydrogel was lost after 14 days in the weight loss test. Blood compatibility and MTT assay showed that hydrogels were nontoxic and improved cell proliferation. In vivo test showed that Alginate/Chitosan/0.1%4-Methylcatechol improved wound healing and the results were significantly better than the gauze-treated wound. Our results showed dose depending effect of 4-Methylcatechol on wound healing. This study shows the treatment effect of 4-Methylcatechol on wound healing and the possibility of using it for treating skin injuries.

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References

  1. Nyame TT, Chiang HA, Leavitt T, et al. Tissue-engineered skin substitutes. Plast Reconstr Surg. 2015;136(6):1379–88.

    Google Scholar 

  2. Lazarus GS, Cooper DM, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Wound Repair Regen. 1994;2(3):165–70.

    Google Scholar 

  3. Chaudhari AA, Vig K, Baganizi DR, et al. Future prospects for scaffolding methods and biomaterials in skin tissue engineering: a review. Int J Mol Sci. 2016;17(12):1974.

    Google Scholar 

  4. Mogoşanu GD, Grumezescu AM. Natural and synthetic polymers for wounds and burns dressing. Int J Pharm. 2014;463(2):127–36.

    Google Scholar 

  5. Gonzalez ACDO, Costa TF, Andrade ZDA, et al. Wound healing-A literature review. An Bras Dermatol. 2016;91(5):614–20.

    Google Scholar 

  6. Talikowska M, Fu X, Lisak G. Application of conducting polymers to wound care and skin tissue engineering: a review. Biosensors and Bioelectronics. 2019.

  7. Jaffe L, Wu SC. Dressings, topical therapy, and negative pressure wound therapy. Clin Podiatr Med Surg. 2019;36(3):397–411.

    Google Scholar 

  8. Dhivya S, Padma VV, Santhini E. Wound dressings–a review. BioMedicine. 2015;5(4).

  9. O’brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today. 2011;14(3):88–95.

    Google Scholar 

  10. Carletti E, Motta A, Migliaresi C. Scaffolds for tissue engineering and 3D cell culture: 3D cell culture. Springer; 2011. p. 17–39.

    Google Scholar 

  11. Bendrea A-D, Cianga L, Cianga I. Progress in the field of conducting polymers for tissue engineering applications. J Biomater Appl. 2011;26(1):3–84.

    Google Scholar 

  12. Huynh CT, Lee DS. Controlling the properties of poly (amino ester urethane)–poly (ethylene glycol)–poly (amino ester urethane) triblock copolymer pH/temperature-sensitive hydrogel. Colloid Polym Sci. 2012;290(11):1077–86.

    Google Scholar 

  13. Jeong K-H, Park D, Lee Y-C. Polymer-based hydrogel scaffolds for skin tissue engineering applications: a mini-review. J Polym Res. 2017;24(7):112.

    Google Scholar 

  14. Bagher Z, Ehterami A, Safdel MH, et al. Wound healing with alginate/chitosan hydrogel containing hesperidin in rat model. J Drug Deliv Sci Technol. 2020;55: 101379.

    Google Scholar 

  15. Pereira R, Carvalho A, Vaz DC, et al. Development of novel alginate based hydrogel films for wound healing applications. Int J Biol Macromol. 2013;52:221–30.

    Google Scholar 

  16. Thu H-E, Zulfakar MH, Ng S-F. Alginate based bilayer hydrocolloid films as potential slow-release modern wound dressing. Int J Pharm. 2012;434(1–2):375–83.

    Google Scholar 

  17. Karimi S, Bagher Z, Najmoddin N, et al. Alginate-magnetic short nanofibers 3D composite hydrogel enhances the encapsulated human olfactory mucosa stem cells bioactivity for potential nerve regeneration application. Int J Biol Macromol. 2021;167:796–806.

    Google Scholar 

  18. Pereira R, Mendes A, Bártolo P. Alginate/Aloe vera hydrogel films for biomedical applications. Procedia CIRP. 2013;5:210–5.

    Google Scholar 

  19. Ribeiro MP, Espiga A, Silva D, et al. Development of a new chitosan hydrogel for wound dressing. Wound Repair Regen. 2009;17(6):817–24.

    Google Scholar 

  20. Garakani SS, Khanmohammadi M, Atoufi Z, et al. Fabrication of chitosan/agarose scaffolds containing extracellular matrix for tissue engineering applications. Int J Biol Macromol. 2020;143:533–45.

    Google Scholar 

  21. Hilmi M, Bakar A, Halim AS, et al. Chitosan dermal substitute and chitosan skin substitute contribute to accelerated full-thickness wound healing in irradiated rats. BioMed Res Int. 2013;2013.

  22. Garakani SS, Davachi SM, Bagher Z, et al. Fabrication of chitosan/polyvinylpyrrolidone hydrogel scaffolds containing PLGA microparticles loaded with dexamethasone for biomedical applications. Int J Biol Macromol. 2020;164:356–70.

    Google Scholar 

  23. Murakami K, Aoki H, Nakamura S, et al. Hydrogel blends of chitin/chitosan, fucoidan and alginate as healing-impaired wound dressings. Biomaterials. 2010;31(1):83–90.

    Google Scholar 

  24. Torelli-Souza RR, Cavalcante Bastos LA, Nunes HG, et al. Sustained release of an antitumoral drug from alginate-chitosan hydrogel beads and its potential use as colonic drug delivery. J Appl Polym Sci. 2012;126(S1):E409–18.

    Google Scholar 

  25. Applová L, Karlíčková J, Warncke P, et al. 4-methylcatechol, a flavonoid metabolite with potent antiplatelet effects. Mol Nutr Food Res. 2019;63(20):1900261.

    Google Scholar 

  26. Thiede H-M, Kehr W. 4-methylcatechol Derivatives and Uses Thereof. Google Patents; 2019.

  27. Hsieh Y-L, Lin W-M, Lue J-H, et al. Effects of 4-methylcatechol on skin reinnervation: promotion of cutaneous nerve regeneration after crush injury. J Neuropathol Exp Neurol. 2009;68(12):1269–81.

    Google Scholar 

  28. Saita K, Ohi T, Hanaoka Y, et al. Effects of 4-methylcatechol, a stimulator of endogenous nerve growth factor synthesis, on experimental acrylamide-induced neuropathy in rats. Neurotoxicology. 1995;16(3):403–12.

    Google Scholar 

  29. Rahmati M, Ehterami A, Saberani R, et al. Improving sciatic nerve regeneration by using alginate/chitosan hydrogel containing berberine. Drug Deliv Transl Res. 2020:1–11.

  30. Abbaszadeh-Goudarzi G, Haghi-Daredeh S, Ehterami A, et al. Evaluating effect of alginate/chitosan hydrogel containing 4-Methylcatechol on peripheral nerve regeneration in rat model. Int J Polym Mater Polym Biomater. 2020:1–10.

  31. Ehterami A, Salehi M, Farzamfar S, et al. Chitosan/alginate hydrogels containing Alpha-tocopherol for wound healing in rat model. J Drug Deliv Sci Technol. 2019.

  32. Ehterami A, Salehi M, Farzamfar S, et al. In vitro and in vivo study of PCL/collagen wound dressing loaded with insulin-chitosan nanoparticles on cutaneous wound healing in rats model. Int J Biol Macromol. 2018.

  33. Salehi M, Vaez A, Naseri-Nosar M, et al. Naringin-loaded Poly (ε-caprolactone)/gelatin electrospun mat as a potential wound dressing: in vitro and in vivo evaluation. Fibers Polym. 2018;19(1):125–34.

    Google Scholar 

  34. Feng G, Nguyen TD, Yi X, et al. Evaluation of long-term inflammatory responses after implantation of a novel fully bioabsorbable scaffold composed of poly-l-lactic acid and amorphous calcium phosphate nanoparticles. J Nanomater. 2018;2018.

  35. Liao J, Jia Y, Wang B, et al. Injectable hybrid poly (ε-caprolactone)-b-poly (ethylene glycol)-b-poly (ε-caprolactone) porous microspheres/alginate hydrogel cross-linked by calcium gluconate crystals deposited in the pores of microspheres improved skin wound healing. ACS Biomater Sci Eng. 2018;4(3):1029–36.

    Google Scholar 

  36. Varaprasad K, Jayaramudu T, Kanikireddy V, et al. Alginate-based composite materials for wound dressing application: a mini review. Carbohydr Polym. 2020:116025.

  37. Das S, Pati F, Choi Y-J, et al. Bioprintable, cell-laden silk fibroin–gelatin hydrogel supporting multilineage differentiation of stem cells for fabrication of three-dimensional tissue constructs. Acta Biomater. 2015;11:233–46.

    Google Scholar 

  38. Karri VVSR, Kuppusamy G, Talluri SV, et al. Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing. Int J Biol Macromol. 2016;93:1519–29.

    Google Scholar 

  39. Mndlovu H, du Toit LC, Kumar P, et al. Development of a fluid-absorptive alginate-chitosan bioplatform for potential application as a wound dressing. Carbohyd Polym. 2019;222: 114988.

    Google Scholar 

  40. Venkatesan J, Lee J-Y, Kang DS, et al. Antimicrobial and anticancer activities of porous chitosan-alginate biosynthesized silver nanoparticles. Int J Biol Macromol. 2017;98:515–25.

    Google Scholar 

  41. Miguel SP, Moreira AF, Correia IJ. Chitosan based-asymmetric membranes for wound healing: a review. Int J Biol Macromol. 2019;127:460–75.

    Google Scholar 

  42. Hsieh Y-L, Kan H-W, Chiang H, et al. Distinct TrkA and Ret modulated negative and positive neuropathic behaviors in a mouse model of resiniferatoxin-induced small fiber neuropathy. Exp Neurol. 2018;300:87–99.

    Google Scholar 

  43. Thiede H-M, Kehr W. 4-methylcatechol Derivatives and Uses Thereof. Google Patents; 2016.

  44. Furukawa Y, Urano T, Minamimura M, et al. 4-Methylcatechol-induced heme oxygenase-1 exerts a protective effect against oxidative stress in cultured neural stem/progenitor cells via PI3 kinase/Akt pathway. Biomed Res. 2010;31(1):45–52.

    Google Scholar 

  45. Hung S-Y, Liou H-C, Fu W-M. The mechanism of heme oxygenase-1 action involved in the enhancement of neurotrophic factor expression. Neuropharmacology. 2010;58(2):321–9.

    Google Scholar 

  46. Li J, Mooney DJ. Designing hydrogels for controlled drug delivery. Nat Rev Mater. 2016;1(12):1–17.

    Google Scholar 

  47. Yannas I, Lee E, Orgill DP, et al. Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. Proc Natl Acad Sci. 1989;86(3):933–7.

    Google Scholar 

  48. O’Brien FJ, Harley BA, Yannas IV, et al. The effect of pore size on cell adhesion in collagen-GAG scaffolds. Biomaterials. 2005;26(4):433–41.

    Google Scholar 

  49. Ahmadi F, Oveisi Z, Samani SM, et al. Chitosan based hydrogels: characteristics and pharmaceutical applications. Res Pharm Sci. 2015;10(1):1.

    Google Scholar 

  50. Caló E, Khutoryanskiy VV. Biomedical applications of hydrogels: a review of patents and commercial products. Eur Polymer J. 2015;65:252–67.

    Google Scholar 

  51. Venkatesan J, Bhatnagar I, Kim S-K. Chitosan-alginate biocomposite containing fucoidan for bone tissue engineering. Mar Drugs. 2014;12(1):300–16.

    Google Scholar 

  52. Prang P, Müller R, Eljaouhari A, et al. The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels. Biomaterials. 2006;27(19):3560–9.

    Google Scholar 

  53. Jagetia GC, Ravikiran P. Acceleration of wound repair and regeneration by Nigella sativa in the deep dermal excision wound of mice whole body exposed to different doses of γ-radiation. Am Res J Med Surg. 2015;1(3):1–17.

    Google Scholar 

  54. Senger DR, Cao S. Diabetic wound healing and activation of Nrf2 by herbal medicine. J Nat Sci. 2016;2(11).

  55. Ehterami A, Salehi M, Farzamfar S, et al. A promising wound dressing based on alginate hydrogels containing vitamin D3 cross-linked by calcium carbonate/d-glucono-δ-lactone. Biomed Eng Lett. 2020:1–11.

  56. Salehi M, Ehterami A, Farzamfar S, et al. Accelerating healing of excisional wound with alginate hydrogel containing naringenin in rat model. Drug Deliv Transl Res. 2020:1–12.

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Acknowledgements

The present study was supported by Shahroud University of Medical Sciences, Shahroud, Iran (Grant No. 97151).

Funding

The present study was supported by Shahroud University of Medical Sciences, Shahroud, Iran (Grant No. 97151).

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Authors and Affiliations

  1. Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Jilla Majidi Ghatar, Simin Nazarnezhad, Maryam Sadat Hassani, Nariman Rezaei Kolarijani & Solmaz Mahami

  2. Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland

    Arian Ehterami

  3. Health Technology Incubator Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Majid Salehi

  4. Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Majid Salehi

  5. Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Majid Salehi

  6. Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Majid Salehi

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  1. Jilla Majidi Ghatar
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Correspondence to Majid Salehi.

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Animal experiments were approved by the ethics committee of the Shahroud university of medical sciences (ethical code: IR.SHMU.REC.1397.167) and were carried out in accordance with the university’s guidelines.

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Majidi Ghatar, J., Ehterami, A., Nazarnezhad, S. et al. A novel hydrogel containing 4-methylcatechol for skin regeneration: in vitro and in vivo study. Biomed. Eng. Lett. 13, 429–439 (2023). https://doi.org/10.1007/s13534-023-00273-z

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