Skip to main content
Log in

Gelatin-based hydrogel functionalized with taurine moieties for in vivo skin tissue regeneration

  • Research Article
  • Published:
Bio-Design and Manufacturing Aims and scope Submit manuscript

Abstract

Functionalized hydrogels stimulate the migration and morphogenesis of endothelial cells (ECs) and are useful substrates for wound healing. The present study investigates the feasibility of covalent conjugation of taurine (Tau) on a gelatin-based hydrogel. This hydrogel is expected to maintain positive charged growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factors (VEGFs) near ECs within the hydrogel microenvironment. The gelatin was conjugated with hydroxyl phenol (Ph) and Tau moieties, and in following that Ph residues were crosslinked through a horseradish peroxidase-catalyzed reaction. The migration characteristics of ECs were analyzed by scratch migration assay and microparticle-based cell migration assay. Cellular morphology and amounts of angiopoietin 1 (Ang 1), bFGF, and VEGF proteins were evaluated for encapsulated cells. The potential of synthesized hydrogels in wound healing was assessed by the percentage of reduction from the original wound size and histopathological analyses of rat skin. The incorporated Tau molecules within the hydrogel remained stable through covalent bonds during incubation. During extended incubation, the gelatin-based hydrogel conjugated with Tau improved the migration distance and number of existing migrated ECs. Immobilized Tau within the gelatin-based hydrogel induced high motility of ECs, accompanied by robust cytoskeleton extension and a cell subpopulation that expressed CD44 and CD31 receptors as well as enhancement of Ang 1, bFGF, and VEGF. We found that injectable Gel-Ph-Tau effectively improves wound-healing parameters.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Dong RN, Guo BL (2021) Smart wound dressings for wound healing. Nano Today 41:101290. https://doi.org/10.1016/j.nantod.2021.101290

    Article  Google Scholar 

  2. Masson-Meyers DS, TaM A, Caetano GF et al (2020) Experimental models and methods for cutaneous wound healing assessment. Int J Exp Pathol 101(1–2):21–37. https://doi.org/10.1111/iep.12346

    Article  Google Scholar 

  3. Farahani M, Shafiee A (2021) Wound healing: from passive to smart dressings. Adv Healthc Mater 10(16):e2100477. https://doi.org/10.1002/adhm.202100477

    Article  Google Scholar 

  4. Liang YP, He JH, Guo BL (2021) Functional hydrogels as wound dressing to enhance wound healing. ACS Nano 15(8):12687–12722. https://doi.org/10.1021/acsnano.1c04206

    Article  Google Scholar 

  5. Zhang SH, Hou JY, Yuan QJ et al (2020) Arginine derivatives assist dopamine-hyaluronic acid hybrid hydrogels to have enhanced antioxidant activity for wound healing. Chem Eng J 392:123775. https://doi.org/10.1016/j.cej.2019.123775

    Article  Google Scholar 

  6. Rodrigues M, Kosaric N, Bonham CA et al (2019) Wound healing: a cellular perspective. Physiol Rev 99(1):665–706. https://doi.org/10.1152/physrev.00067.2017

    Article  Google Scholar 

  7. Han G, Ceilley R (2017) Chronic wound healing: a review of current management and treatments. Adv Ther 34(3):599–610. https://doi.org/10.1007/s12325-017-0478-y

    Article  Google Scholar 

  8. Khanmohammadi M, Sakai S, Taya M (2019) Characterization of encapsulated cells within hyaluronic acid and alginate microcapsules produced via horseradish peroxidase-catalyzed crosslinking. J Biomat Sci-Polym E 30(4):295–307. https://doi.org/10.1080/09205063.2018.1562637

    Article  Google Scholar 

  9. Wang P, Huang BS, Horng HC et al (2018) Wound healing. J Chin Med Assoc 2(81):94–101

    Article  Google Scholar 

  10. Rieger KA, Birch NP, Schiffman JD (2013) Designing electrospun nanofiber mats to promote wound healing - a review. J Mater Chem B 1(36):4531–4541. https://doi.org/10.1039/c3tb20795a

    Article  Google Scholar 

  11. Alven S, Aderibigbe B (2019) Combination therapy strategies for the treatment of malaria. Molecules 24(19):3601. https://doi.org/10.3390/molecules24193601

    Article  Google Scholar 

  12. Opt Veld RC, van den Boomen OI, Lundvig DMS et al (2018) Thermosensitive biomimetic polyisocyanopeptide hydrogels may facilitate wound repair. Biomaterials 181(392):401. https://doi.org/10.1016/j.biomaterials.2018.07.038

    Article  Google Scholar 

  13. Lin KS, Wang SY, Fan LJ et al (2017) Adipose-derived stem cells seeded in pluronic F-127 hydrogel promotes diabetic wound healing. J Surg Res 217:63–74. https://doi.org/10.1016/j.jss.2017.04.032

    Article  Google Scholar 

  14. Zhu JM, Marchant RE (2011) Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devic 8(5):607–626. https://doi.org/10.1586/Erd.11.27

    Article  Google Scholar 

  15. Catanzano O, Quaglia F, Boateng JS (2021) Wound dressings as growth factor delivery platforms for chronic wound healing. Expert Opin Drug Del 18(6):737–759. https://doi.org/10.1080/17425247.2021.1867096

    Article  Google Scholar 

  16. Jo H, Yoon M, Gajendiran M et al (2020) Recent strategies in fabrication of gradient hydrogels for tissue engineering applications. Macromol Biosci 20(3):1900300. https://doi.org/10.1002/mabi.201900300

    Article  Google Scholar 

  17. Hsu YY, Liu KL, Yeh HH et al (2019) Sustained release of recombinant thrombomodulin from cross-linked gelatin/hyaluronic acid hydrogels potentiate wound healing in diabetic mice. Eur J Pharm Biopharm 135:61–71. https://doi.org/10.1016/j.ejpb.2018.12.007

    Article  Google Scholar 

  18. Dang LH, Huynh NT, Pham NO et al (2019) Injectable nanocurcumin-dispersed gelatin-pluronic nanocomposite hydrogel platform for burn wound treatment. B Mater Sci 42(2):71. https://doi.org/10.1007/s12034-019-1745-0

    Article  Google Scholar 

  19. Khamrai M, Banerjee SL, Paul S et al (2019) Curcumin entrapped gelatin/ionically modified bacterial cellulose based self-healable hydrogel film: an eco-friendly sustainable synthesis method of wound healing patch. Int J Biol Macromol 122:940–953. https://doi.org/10.1016/j.ijbiomac.2018.10.196

    Article  Google Scholar 

  20. Mansoori-Kermani A, Khalighi S, Akbarzadeh I et al (2022) Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer. Mater Today Bio 16:100349. https://doi.org/10.1016/j.mtbio.2022.100349

    Article  Google Scholar 

  21. Singaravelu S, Ramanathan G, Raja MD et al (2016) Biomimetic interconnected porous keratin–fibrin–gelatin 3D sponge for tissue engineering application. Int J Biol Macromol 86:810–819. https://doi.org/10.1016/j.ijbiomac.2016.02.021

    Article  Google Scholar 

  22. Benskin LL (2018) Evidence for polymeric membrane dressings as a unique dressing subcategory, using pressure ulcers as an example. Adv Wound Care 7(12):419–426. https://doi.org/10.1089/wound.2018.0822

    Article  Google Scholar 

  23. Ye HL, Cheng JW, Yu K (2019) In situ reduction of silver nanoparticles by gelatin to obtain porous silver nanoparticle/chitosan composites with enhanced antimicrobial and wound-healing activity. Int J Biol Macromol 121:633–642. https://doi.org/10.1016/j.ijbiomac.2018.10.056

    Article  Google Scholar 

  24. Ndlovu SP, Ngece K, Alven S et al (2021) Gelatin-based hybrid scaffolds: promising wound dressings. Polymers 13(17):2959. https://doi.org/10.3390/polym13172959

    Article  Google Scholar 

  25. Dias JR, Baptista-Silva S, De Oliveira CMT et al (2017) In situ crosslinked electrospun gelatin nanofibers for skin regeneration. Eur Polym J 95:161–173. https://doi.org/10.1016/j.eurpolymj.2017.08.015

    Article  Google Scholar 

  26. Rath G, Hussain T, Chauhan G et al (2016) Development and characterization of cefazolin loaded zinc oxide nanoparticles composite gelatin nanofiber mats for postoperative surgical wounds. Mat Sci Eng C Mater 58:242–253. https://doi.org/10.1016/j.msec.2015.08.050

    Article  Google Scholar 

  27. Campiglio CE, Contessi Negrini N, Fare S et al (2019) Cross-linking strategies for electrospun gelatin scaffolds. Materials 12(15):2476. https://doi.org/10.3390/ma12152476

    Article  Google Scholar 

  28. Badali E, Hosseini M, Mohajer M et al (2021) Enzymatic crosslinked hydrogels for biomedical application. Polym Sci Ser A 63(Suppl 1):S1–S22. https://doi.org/10.1134/S0965545x22030026

    Article  Google Scholar 

  29. Khanmohammadi M, Dastjerdi MB, Ai A et al (2018) Horseradish peroxidase-catalyzed hydrogelation for biomedical applications. Biomater Sci 6(6):1286–1298. https://doi.org/10.1039/c8bm00056e

    Article  Google Scholar 

  30. Davachi SM, Haramshahi SMA, Akhavirad SA et al (2022) Development of chitosan/hyaluronic acid hydrogel scaffolds via enzymatic reaction for cartilage tissue engineering. Mater Today Commun 30:103230. https://doi.org/10.1016/j.mtcomm.2022.103230

    Article  Google Scholar 

  31. Badali E, Hosseini M, Varaa N et al (2022) Production of uniform size cell-enclosing silk derivative vehicles through coaxial microfluidic device and horseradish crosslinking reaction. Eur Polym J 172:111237. https://doi.org/10.1016/j.eurpolymj.2022.111237

    Article  Google Scholar 

  32. Liu Y, Wong CW, Chang SW et al (2021) An injectable, self-healing phenol-functionalized chitosan hydrogel with fast gelling property and visible light-crosslinking capability for 3D printing. Acta Biomater 122:211–219. https://doi.org/10.1016/j.actbio.2020.12.051

    Article  Google Scholar 

  33. Deng LL, Du CZ, Song PY et al (2021) The role of oxidative stress and antioxidants in diabetic wound healing. Oxid Med Cell Longev 2021:8852759. https://doi.org/10.1155/2021/8852759

    Article  Google Scholar 

  34. Xu ZJ, Han SY, Gu ZP et al (2020) Advances and impact of antioxidant hydrogel in chronic wound healing. Adv Healthc Mater 9(5):1901502. https://doi.org/10.1002/adhm.201901502

    Article  Google Scholar 

  35. Zdunska K, Dana A, Kolodziejczak A et al (2018) Antioxidant properties of ferulic acid and its possible application. Skin Pharmacol Phys 31(6):332–336. https://doi.org/10.1159/000491755

    Article  Google Scholar 

  36. Farzamfar S, Naseri-Nosar M, Samadian H et al (2018) Taurine-loaded poly (ε-caprolactone)/gelatin electrospun mat as a potential wound dressing material: in vitro and in vivo evaluation. J Bioact Compat Pol 33(3):282–294. https://doi.org/10.1177/0883911517737103

    Article  Google Scholar 

  37. Vittorazzi C, Endringer DC, De Andrade TU et al (2016) Antioxidant, antimicrobial and wound healing properties of Struthanthus vulgaris. Pharm Biol 54(2):331–337. https://doi.org/10.3109/13880209.2015.1040515

    Article  Google Scholar 

  38. Li M, Chen J, Shi MT et al (2019) Electroactive anti-oxidant polyurethane elastomers with shape memory property as non-adherent wound dressing to enhance wound healing. Chem Eng J 375:121999. https://doi.org/10.1016/j.cej.2019.121999

    Article  Google Scholar 

  39. Qu J, Zhao X, Liang YP et al (2018) Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing. Biomaterials 183:185–199. https://doi.org/10.1016/j.biomaterials.2018.08.044

    Article  Google Scholar 

  40. Lambert IH, Kristensen DM, Holm JB et al (2015) Physiological role of taurine–from organism to organelle. Acta Physiol 213(1):191–212. https://doi.org/10.1111/apha.12365

    Article  Google Scholar 

  41. Goodarzi A, Khanmohammadi M, Ebrahimi-Barough S et al (2019) Alginate-based hydrogel containing taurine-loaded chitosan nanoparticles in biomedical application. Arch Neurosci 6(2):e86349. https://doi.org/10.5812/ans.86349

    Article  Google Scholar 

  42. Khorani M, Bobe G, Matthews DG et al (2022) The impact of the hAPP695SW transgene and associated amyloid-β accumulation on murine hippocampal biochemical pathways. J Alzheimers Dis 85(4):1601–1619. https://doi.org/10.3233/Jad-215084

    Article  Google Scholar 

  43. Khanmohammadi M, Sakai S, Taya M (2017) Impact of immobilizing of low molecular weight hyaluronic acid within gelatin-based hydrogel through enzymatic reaction on behavior of enclosed endothelial cells. Int J Biol Macromol 97:308–316. https://doi.org/10.1016/j.ijbiomac.2016.12.088

    Article  Google Scholar 

  44. Wu L, Zhang QW, Li Y et al (2021) Collagen sponge prolongs taurine release for improved wound healing through inflammation inhibition and proliferation stimulation. Ann Transl Med 9(12):1010. https://doi.org/10.21037/atm-21-2739

    Article  Google Scholar 

  45. Comino-Sanz IM, Lopez-Franco MD, Castro B et al (2021) The role of antioxidants on wound healing: a review of the current evidence. J Clin Med 10(16):3558. https://doi.org/10.3390/jcm10163558

    Article  Google Scholar 

  46. Baek YY, Cho DH, Choe J et al (2012) Extracellular taurine induces angiogenesis by activating ERK-, Akt-, and FAK-dependent signal pathways. Eur J Pharmacol 674(2–3):188–199. https://doi.org/10.1016/j.ejphar.2011.11.022

    Article  Google Scholar 

  47. Khoshfetrat AB, Khanmohammadi M, Sakai S et al (2016) Enzymatically-gellable galactosylated chitosan: hydrogel characteristics and hepatic cell behavior. Int J Biol Macromol 92:892–899. https://doi.org/10.1016/j.ijbiomac.2016.08.003

    Article  Google Scholar 

  48. Khanmohammadi M, Sakai S, Ashida T et al (2016) Production of hyaluronic-acid-based cell-enclosing microparticles and microcapsules via enzymatic reaction using a microfluidic system. J Appl Polym Sci 133(16):43107. https://doi.org/10.1002/app.43107

    Article  Google Scholar 

  49. Firouzi N, Khoshfetrat AB, Kazemi D (2020) Enzymatically gellable gelatin improves nano-hydroxyapatite-alginate microcapsule characteristics for modular bone tissue formation. J Biomed Mater Res A 108(2):340–350. https://doi.org/10.1002/jbm.a.36820

    Article  Google Scholar 

  50. Wu M, Du Y, Liu YW et al (2014) Low molecular weight hyaluronan induces lymphangiogenesis through LYVE-1-mediated signaling pathways. PLoS ONE 9(3):e92857. https://doi.org/10.1371/journal.pone.0092857

    Article  Google Scholar 

  51. Karimifard S, Rezaei N, Jamshidifar E et al (2022) pH-responsive chitosan-adorned niosome nanocarriers for co-delivery of drugs for breast cancer therapy. ACS Appl Nano Mater 5(7):8811–8825. https://doi.org/10.1021/acsanm.2c00861

    Article  Google Scholar 

  52. Vernon RB, Sage EH (1999) A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices. Microvasc Res 57(2):118–133. https://doi.org/10.1006/mvre.1998.2122

    Article  Google Scholar 

  53. Yang XM, Sarvestani SK, Moeinzadeh S et al (2013) Effect of CD44 binding peptide conjugated to an engineered inert matrix on maintenance of breast cancer stem cells and tumorsphere formation. PLoS ONE 8(3):e59147. https://doi.org/10.1371/journal.pone.0059147

    Article  Google Scholar 

  54. Reno C, Marchuk L, Sciore P et al (1997) Rapid isolation of total RNA from small samples of hypocellular, dense connective tissues. Biotechniques 22(6):1082. https://doi.org/10.2144/97226bm16

    Article  Google Scholar 

  55. Guo R, Xu SJ, Ma L et al (2011) The healing of full-thickness burns treated by using plasmid DNA encoding VEGF-165 activated collagen–chitosan dermal equivalents. Biomaterials 32(4):1019–1031. https://doi.org/10.1016/j.biomaterials.2010.08.087

    Article  Google Scholar 

  56. Badali E, Goodarzi A, Khodayari H et al (2022) Layered dermal reconstitution through epigallocatechin 3-gallate loaded chitosan nanoparticle within enzymatically crosslinked polyvinyl alcohol/collagen fibrous mat. J Biomater Appl 37(3):502–516. https://doi.org/10.1177/08853282221104175

    Article  Google Scholar 

  57. Salehi M, Zamiri S, Samadian H et al (2021) Chitosan hydrogel loaded with Aloe vera gel and tetrasodium ethylenediaminetetraacetic acid (EDTA) as the wound healing material: in vitro and in vivo study. J Appl Polym Sci 138(16):e50225. https://doi.org/10.1002/app.50225

    Article  Google Scholar 

  58. Pardue EL, Ibrahim S, Ramamurthi A (2008) Role of hyaluronan in angiogenesis and its utility to angiogenic tissue engineering. Organogenesis 4(4):203–214. https://doi.org/10.4161/org.4.4.6926

    Article  Google Scholar 

  59. Chen WS, He SP, Xiang DM (2021) Hypoxia-induced retinal pigment epithelium cell-derived bFGF promotes the migration and angiogenesis of HUVECs through regulating TGF-β1/smad2/3 pathway. Cancer Lett 328(1):18–26. https://doi.org/10.1016/j.gene.2021.145695

    Article  Google Scholar 

  60. Fagiani E, Christofori G (2013) Angiopoietins in angiogenesis. Cancer Lett 328(1):18–26. https://doi.org/10.1016/j.canlet.2012.08.018

    Article  Google Scholar 

  61. Napoli S, Scuderi C, Gattuso G et al (2020) Functional roles of matrix metalloproteinases and their inhibitors in melanoma. Cells 9(5):1511. https://doi.org/10.3390/cells9051151

    Article  Google Scholar 

  62. Kandhwal M, Behl T, Singh S et al (2022) Role of matrix metalloproteinase in wound healing. Am J Transl Res 14(7):4391–4405

    Google Scholar 

  63. Tampa M, Georgescu SR, Mitran MI et al (2021) Current perspectives on the role of matrix metalloproteinases in the pathogenesis of basal cell carcinoma. Biomolecules 11(6):903. https://doi.org/10.3390/biom11060903

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

FR, AG (Aida Goodarzi), and MK contributed to conceptualization; FN, NA, FR, SS, and SH contributed to formal analysis and investigation; NA, FN, and AG (Arash Goodarzi) contributed to writing—original draft preparation; AG (Arash Goodarzi) and MK contributed to supervision.

Corresponding authors

Correspondence to Mehdi Khanmohammadi or Arash Goodarzi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All institutional and national guidelines for the care and use of laboratory animals were followed. Animal use and care were approved with National Ethics Committee of Fasa University of Medical Sciences (Ethical code: IR.FUMS.REC.1399.160) and were performed in accordance with the university’s guidelines. Furthermore, all animal experiments comply with the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978).

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rahimi, F., Ahmadkhani, N., Goodarzi, A. et al. Gelatin-based hydrogel functionalized with taurine moieties for in vivo skin tissue regeneration. Bio-des. Manuf. 6, 284–297 (2023). https://doi.org/10.1007/s42242-022-00227-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42242-022-00227-x

Keywords

Navigation