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Preparation of porous alginate-based smart dressings used in real-time monitoring of pH in chronic wounds by evaluating two fabrication routes: freeze-drying vs. electrospinning

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Abstract

Timely recognition the on-set of infection is very important for management and treatment of wounds. Regarding various biomarkers, pH of the wound milieu could be mentioned as one of the most effective tools for this purpose. In this work, some smart dressings were fabricated for detection of the change of pH in wounds due to infection. To do this, phenol red as a pH-indicator dye was incorporated into an alginate-based matrix. Two groups of dressings containing phenol red were prepared via freeze-drying and electrospinning techniques. Pore size of the freeze-dried dressings as well as mean diameter and pores size of the electrospun samples were estimated to be 62.24 μm, 204 nm, and 2.03 μm, respectively. Remarkable fluid absorption was determined for both electrospun (2125%) and freeze-dried (860%) samples. Measurements according to CIE L*a*b* and RGB color spaces revealed that the color difference between samples in buffers with different pHs of 4, 6, 7, 8, 9, and 10 could be distinguished well by the naked eye. In spite of less fluid absorption for the freeze-dried samples in comparison to electrospun ones, they exhibited better resistance to dye leaching and preserved their structure better after soaking in different pH buffers. Biological evaluation using adipose-derived mesenchymal stem cells, revealed no cytotoxic effects for samples containing phenol red. Moreover, the alginate matrix provides proper conditions for attachment as well as proliferation of the cells. Overall, the results suggest that samples which were fabricated through freeze-drying method could be considered as good candidates for application in management and monitoring of chronic wounds.

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References

  1. S. Ayu Lestari, M. Armayah, Modern Commercial Wound Dressings and Introducing New Wound Dressings for Wound Healing: A Revie, Polymerization. 8 (2016) 65–80

  2. A.R. Sadeghi-Avalshahr, S. Nokhasteh, A.M. Molavi, N. Mohammad-Pour, M. Sadeghi, Tailored PCL scaffolds as skin substitutes using sacrificial PVP fibers and collagen/chitosan blends. Int. J. Mol. Sci. 21 (2020). https://doi.org/10.3390/ijms21072311

  3. Functional wound dressings.pdf, (n.d.)

  4. L. Liu, X. Li, M. Nagao, A.L. Elias, R. Narain, H.J. Chung, A pH-Indicating colorimetric tough hydrogel patch towards applications in a substrate for smart wound dressings, polymers (Basel). 9 (2017). https://doi.org/10.3390/polym9110558

  5. Color changing of, smart fibrous materials for naked eye real-time monitoring of wound pH.pdf, (n.d.)

  6. M.B. Bazbouz, G. Tronci, Two-layer electrospun system enabling wound exudate management and visual infection response. Sens. (Switzerland). 19 (2019). https://doi.org/10.3390/s19050991

  7. J. Chalitangkoon, P. Monvisade, Synthesis of chitosan-based polymeric dyes as colorimetric pH-sensing materials: potential for food and biomedical applications. Carbohydr. Polym. 260 (2021). https://doi.org/10.1016/j.carbpol.2021.117836

  8. A.A. Arafa, A.A. Nada, A.Y. Ibrahim, P. Sajkiewicz, M.K. Zahran, O.A. Hakeim, Preparation and characterization of smart therapeutic pH-sensitive wound dressing from red cabbage extract and chitosan hydrogel. Int. J. Biol. Macromol. 182, 1820–1831 (2021). https://doi.org/10.1016/j.ijbiomac.2021.05.167

    Article  CAS  PubMed  Google Scholar 

  9. P. Kassal, M. Zubak, G. Scheipl, G.J. Mohr, M.D. Steinberg, I. Murković, Steinberg, Smart bandage with wireless connectivity for optical monitoring of pH. Sens. Actuators B Chem. 246, 455–460 (2017). https://doi.org/10.1016/j.snb.2017.02.095

    Article  CAS  Google Scholar 

  10. C. Gamerith, D. Luschnig, A. Ortner, N. Pietrzik, J.H. Guse, M. Burnet, M. Haalboom, J. van der Palen, A. Heinzle, E. Sigl, G.M. Gübitz, pH-responsive materials for optical monitoring of wound status. Sens. Actuators B Chem. 301 (2019). https://doi.org/10.1016/j.snb.2019.126966

  11. A. Truskewycz, V.K. Truong, A.S. Ball, S. Houshyar, N. Nassar, H. Yin, B.J. Murdoch, I. Cole, Fluorescent Magnesium Hydroxide Nanosheet Bandages with tailored Properties for Biocompatible Antimicrobial Wound Dressings and pH monitoring. ACS Appl. Mater. Interfaces. 13, 27904–27919 (2021). https://doi.org/10.1021/acsami.1c05908

    Article  CAS  PubMed  Google Scholar 

  12. S. Li, H. Vu, J. Senkowsky, W. Hu, L. Tang, A near-infrared fluorescent pH sensing film for wound milieu pH monitoring. Exp. Dermatol. 29, 107–111 (2020). https://doi.org/10.1111/exd.14046

    Article  CAS  PubMed  Google Scholar 

  13. A. Agarwal, A. Raheja, T.S. Natarajan, T.S. Chandra, Sensors and actuators B: Chemical Development of universal pH sensing electrospun nanofibers. Sens. Actuators B Chem. 161, 1097–1101 (2012)

    Article  CAS  Google Scholar 

  14. alginate 2021.pdf, (n.d.)

  15. G. Schoukens, Bioactive dressings to promote wound healing. Adv. Text. Wound Care. 135–167 (2019). https://doi.org/10.1016/b978-0-08-102192-7.00005-9

  16. K.Y. Lee, D.J. Mooney, Alginate: Properties and biomedical applications. Prog Polym. Sci. 37, 106–126 (2012). https://doi.org/10.1016/j.progpolymsci.2011.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. S.G. Reddy, A.-A.S. Product, Its Properties and Applications, Prop. Appl. Alginates. (2021). https://doi.org/10.5772/INTECHOPEN.98831

    Article  Google Scholar 

  18. Perspectives of chitosan, and alginate membranes for biomedical applications | Request PDF, (n.d.)

  19. M.I. Neves, L. Moroni, C.C. Barrias, Modulating Alginate Hydrogels for Improved Biological Performance as Cellular 3D microenvironments, Front. Bioeng. Biotechnol. 8, 665 (2020). https://doi.org/10.3389/FBIOE.2020.00665/BIBTEX

    Article  Google Scholar 

  20. Alginate, in Wound Dressings.pdf, (n.d.)

  21. S. Dhivya, V.V. Padma, E. Santhini, Wound dressings – a review.pdf, (2015) 24–28

  22. Z.M. Huang, Y.Z. Zhang, M. Kotaki, S. Ramakrishna, A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos. Sci. Technol. 63, 2223–2253 (2003). https://doi.org/10.1016/S0266-3538(03)00178-7

    Article  CAS  Google Scholar 

  23. M.S. Islam, B.C. Ang, A. Andriyana, A.M. Afifi, A review on fabrication of nanofibers via electrospinning and their applications. SN Appl. Sci. 1 (2019). https://doi.org/10.1007/s42452-019-1288-4

  24. N. Bhattarai, D. Edmondson, O. Veiseh, F.A. Matsen, M. Zhang, Electrospun chitosan-based nanofibers and their cellular compatibility. Biomaterials. 26, 6176–6184 (2005). https://doi.org/10.1016/j.biomaterials.2005.03.027

    Article  CAS  PubMed  Google Scholar 

  25. Chap, 10 - Centrifugal Spinning—High Rate Production of Nanofibers.pdf, n.d

  26. L.H. Chong, N.Z. Zarith, N. Sultana, Poly(Caprolactone)/chitosan-based scaffold using freeze drying technique for bone tissue engineering application, 2015 10th Asian Control Conf. Emerg. Control Tech. a Sustain. World, ASCC 2015. (2015). https://doi.org/10.1109/ASCC.2015.7244570

  27. Shukla, FREEZE DRYING PROCESS: A REVIEW Soham Shukla* Department of Pharmaceutical Technology, Patel Pharmacy College, Saffrony Institute of Technology, Near Saffrony Holiday Resort, Ahmedabad-Mehsana Highway, at & Post Linch-384435, Mahesana, Gujarat, Indi. Int. J. Pharm. Sci. Res. 2, 3061–3068 (2011). https://ijpsr.com/bft-article/freeze-drying-process-a-review/?view=fulltext

    CAS  Google Scholar 

  28. C.A. Bonino, M.D. Krebs, C.D. Saquing, S.I. Jeong, K.L. Shearer, E. Alsberg, S.A. Khan, Electrospinning alginate-based nanofibers: from blends to crosslinked low molecular weight alginate-only systems. Carbohydr. Polym. 85, 111–119 (2011). https://doi.org/10.1016/j.carbpol.2011.02.002

    Article  CAS  Google Scholar 

  29. K. Tarun, N. Gobi, Calcium alginate/PVA blended nano fibre matrix for wound dressing. Indian J. Fibre Text. Res. 37, 127–132 (2012)

    CAS  Google Scholar 

  30. S. Alborzi, L.T. Lim, Y. Kakuda, Electrospinning of sodium alginate-pectin ultrafine fibers. J. Food Sci. 75, 100–107 (2010). https://doi.org/10.1111/j.1750-3841.2009.01437.x

    Article  CAS  Google Scholar 

  31. H. Hajiali, J.A. Heredia-Guerrero, I. Liakos, A. Athanassiou, E. Mele, Alginate Nanofibrous Mats with adjustable degradation rate for Regenerative Medicine. Biomacromolecules. 16, 936–943 (2015). https://doi.org/10.1021/bm501834m

    Article  CAS  PubMed  Google Scholar 

  32. M. Castellano, M. Alloisio, R. Darawish, A. Dodero, S. Vicini, Electrospun composite mats of alginate with embedded silver nanoparticles: synthesis and characterization. J. Therm. Anal. Calorim. 137, 767–778 (2019). https://doi.org/10.1007/s10973-018-7979-z

    Article  CAS  Google Scholar 

  33. N. Bhattarai, M. Zhang, Controlled synthesis and structural stability of alginate-based nanofibers. Nanotechnology. 18 (2007). https://doi.org/10.1088/0957-4484/18/45/455601

  34. BS EN, 13726-1-2002.pdf, (n.d.)

  35. CIE_Lab_info.pdf, (n.d.)

  36. H. Wen, W. Xiao, S. Biswas, Z.Q. Cong, X.M. Liu, K.S. Lam, Y.H. Liao, W. Deng, Alginate Hydrogel modified with a ligand interacting with α3β1 integrin receptor promotes the differentiation of 3D neural Spheroids toward Oligodendrocytes in Vitro. ACS Appl. Mater. Interfaces. 11, 5821–5833 (2019). https://doi.org/10.1021/acsami.8b19438

    Article  CAS  PubMed  Google Scholar 

  37. N. Bahrami, A. Farzin, F. Bayat, A. Goodarzi, M. Salehi, R. Karimi, A. Mohamadnia, A. Parhiz, J. Ai, Optimization of 3D Alginate Scaffold Properties with interconnected porosity using freeze-drying method for cartilage tissue Engineering Application. Arch. Neurosci. 6, 4–11 (2019). https://doi.org/10.5812/ans.85122

    Article  Google Scholar 

  38. A. Sergeeva, N. Feoktistova, V. Prokopovic, D. Gorin, D. Volodkin, Design of porous Alginate Hydrogels by Sacrificial CaCO3 templates: pore formation mechanism. Adv. Mater. Interfaces. 2, 1–10 (2015). https://doi.org/10.1002/admi.201500386

    Article  CAS  Google Scholar 

  39. A. Vincent, Study of Porosity of Gelatin-Alginate Hydrogels to Model Brain Study of Porosity of Gelatin-Alginate Hydrogels to Model Brain Matter for Studying Traumatic Brain Injuries Matter for Studying Traumatic Brain Injuries, (2022). https://opencommons.uconn.edu/srhonors_theses/887

  40. V.A. Petrova, A.S. Golovkin, A.I. Mishanin, D.P. Romanov, D.D. Chernyakov, D.N. Poshina, Y.A. Skorik, Cytocompatibility of Bilayer Sca ff olds Electrospun from Nanowhiskers, Chitosan Alginate-chitin. Biomedicines. 8, 305 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. B. Vigani, S. Rossi, G. Sandri, M.C. Bonferoni, G. Milanesi, G. Bruni, F. Ferrari, Coated electrospun alginate-containing fibers as novel delivery systems for regenerative purposes. Int. J. Nanomedicine. 13, 6531–6550 (2018). https://doi.org/10.2147/IJN.S175069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. R. Wongkanya, P. Chuysinuan, C. Pengsuk, S. Techasakul, K. Lirdprapamongkol, J. Svasti, P. Nooeaid, Electrospinning of alginate/soy protein isolated nanofibers and their release characteristics for biomedical applications. J. Sci. Adv. Mater. Devices. 2, 309–316 (2017). https://doi.org/10.1016/j.jsamd.2017.05.010

    Article  Google Scholar 

  43. E. U.M.D.E.C.D, Los, No 主観的健康感を中心とした在宅高齢者における 健康関連指標に関する共分散構造分析 Title, (n.d.).

  44. J. Grenier, H. Duval, F. Barou, P. Lv, B. David, D. Letourneur, Mechanisms of pore formation in hydrogel scaffolds textured by freeze-drying. Acta Biomater. 94, 195–203 (2019). https://doi.org/10.1016/j.actbio.2019.05.070

    Article  CAS  PubMed  Google Scholar 

  45. M. Guastaferro, L. Baldino, E. Reverchon, S. Cardea, Production of porous agarose-based structures: freeze-drying vs. supercritical CO2 drying. Gels. 7 (2021). https://doi.org/10.3390/gels7040198

  46. Z. Zhang, Y. Feng, L. Wang, D. Liu, C. Qin, Y. Shi, A review of preparation methods of porous skin tissue engineering scaffolds. Mater. Today Commun. 32, 104109 (2022). https://doi.org/10.1016/J.MTCOMM.2022.104109

    Article  CAS  Google Scholar 

  47. Y. Zhang, M. Zhang, D. Cheng, S. Xu, C. Du, L. Xie, W. Zhao, Applications of electrospun scaffolds with enlarged pores in tissue engineering. Biomater. Sci. 10, 1423–1447 (2022). https://doi.org/10.1039/D1BM01651B

    Article  CAS  PubMed  Google Scholar 

  48. I. Negut, G. Dorcioman, V. Grumezescu, Scaffolds for Wound Healing Applications, Polymers (Basel). 12 (2020) 1–19. https://doi.org/10.3390/POLYM12092010

  49. A. Deng, Y. Yang, S. Du, Tissue Engineering 3D Porous Scaffolds Prepared from Electrospun Recombinant Human Collagen (RHC) Polypeptides/Chitosan Nanofibers, Appl. Sci. 2021, Vol. 11, Page 5096. 11 (2021) 5096. https://doi.org/10.3390/APP11115096

  50. A. Ahmed, G. Getti, J. Boateng, Ciprofloxacin-loaded calcium alginate wafers prepared by freeze-drying technique for potential healing of chronic diabetic foot ulcers. Drug Deliv. Transl. Res. 8, 1751–1768 (2018). https://doi.org/10.1007/s13346-017-0445-9

    Article  CAS  PubMed  Google Scholar 

  51. T.C. Trevisol, A.R.M. Fritz, S.M.A.G.U. de Souza, A.C.K. Bierhalz, J.A.B. Valle, Alginate and carboxymethyl cellulose in monolayer and bilayer films as wound dressings: Effect of the polymer ratio. J. Appl. Polym. Sci. 136 (2019). https://doi.org/10.1002/app.46941

  52. K.R. Aadil, A. Nathani, C.S. Sharma, N. Lenka, P. Gupta, Fabrication of biocompatible alginate-poly(vinyl alcohol) nanofibers scaffolds for tissue engineering applications. Mater. Technol. 33, 507–512 (2018). https://doi.org/10.1080/10667857.2018.1473234

    Article  CAS  Google Scholar 

  53. T.K.V. Urquiza, O.P. Pérez, M.G. Saldaña, Effect of the cross-linking with calcium ions on the structural and thermo-mechanical properties of alginate films, Mater. Res. Soc. Symp. Proc. 1355 (2011) 16–21. https://doi.org/10.1557/opl.2011.1136

  54. S.Y. Park, W.J. Kim, J.B. Choi, S. Kim, Physical and mechanical properties of alginate-based hydrogel film as carrier for release of acetylthiocholine. Int. J. Precis Eng. Manuf. 19, 129–135 (2018). https://doi.org/10.1007/s12541-018-0015-1

    Article  Google Scholar 

  55. T.M.S. Udenni Gunathilake, Y.C. Ching, K.Y. Ching, C.H. Chuah, L.C. Abdullah, Biomedical and microbiological applications of bio-based porous materials: a review. Polym. (Basel). 9, 1–16 (2017). https://doi.org/10.3390/polym9050160

    Article  CAS  Google Scholar 

  56. D. Wu, F. Xu, B. Sun, R. Fu, H. He, K. Matyjaszewski, Design and preparation of porous polymers. Chem. Rev. 112, 3959–4015 (2012). https://doi.org/10.1021/CR200440Z. /ASSET/IMAGES/CR200440Z.SOCIAL.JPEG_V03

    Article  CAS  PubMed  Google Scholar 

  57. L. De Smet, G. Vancoillie, P. Minshall, K. Lava, I. Steyaert, E. Schoolaert, E. Van De Walle, P. Dubruel, K. De Clerck, R. Hoogenboom, Plasma dye coating as straightforward and widely applicable procedure for dye immobilization on polymeric materials. Nat. Commun. 2018. 91(9), 1–11 (2018). https://doi.org/10.1038/s41467-018-03583-4

    Article  CAS  Google Scholar 

  58. T. De Meyer, I. Steyaert, K. Hemelsoet, R. Hoogenboom, V. Van Speybroeck, K. De Clerck, Halochromic properties of sulfonphthaleine dyes in a textile environment: the influence of substituents. Dye. Pigment. 124, 249–257 (2016). https://doi.org/10.1016/J.DYEPIG.2015.09.007

    Article  Google Scholar 

  59. E. Schoolaert, I. Steyaert, G. Vancoillie, J. Geltmeyer, K. Lava, R. Hoogenboom, K. De Clerck, Blend electrospinning of dye-functionalized chitosan and poly(ε-caprolactone): towards biocompatible pH-sensors. J. Mater. Chem. B 4, 4507–4516 (2016). https://doi.org/10.1039/C6TB00639F

    Article  CAS  PubMed  Google Scholar 

  60. M. Ernst, C. Schmid, E.R. Froesch, Phenol red mimics biological actions of estradiol: enhancement of osteoblast proliferation in vitro and of type I collagen gene expression in bone and uterus of rats in vivo. J. Steroid Biochem. 33, 907–914 (1989). https://doi.org/10.1016/0022-4731(89)90239-2

    Article  CAS  PubMed  Google Scholar 

  61. A. Morgan, D. Babu, B. Reiz, R. Whittal, L.Y.K. Suh, A.G. Siraki, Caution for the routine use of phenol red - it is more than just a pH indicator. Chem. Biol. Interact. 310 (2019). https://doi.org/10.1016/J.CBI.2019.108739

  62. N. Kuncharoenwirat, W. Chatuphonprasert, K. Jarukamjorn, Effect of phenol red on cell cultures. Isan J. Pharm. Sci. IJPS (Isan J. Pharm. Sci). 17, 13–23 (2021). https://doi.org/10.14456/IJPS.2021.2

    Article  Google Scholar 

  63. R. Phenol, powder, BioReagent, cell culture mammalian 143-74-8, (n.d.)

  64. N. Ansari, S. Müller, E.H.K. Stelzer, F. Pampaloni, Quantitative 3D cell-based assay performed with Cellular Spheroids and fluorescence Microscopy. Methods Cell. Biol. 113, 295–309 (2013). https://doi.org/10.1016/B978-0-12-407239-8.00013-6

    Article  CAS  PubMed  Google Scholar 

  65. P. Held, D. Ph, B. Instruments, p p l i c a t i o n o t e Using Phenol Red to Assess pH in Tissue Culture Media, (1966)

  66. L. Bennison, C. Miller, R. Summers, A. Minnis, G. Sussman, W. McGuiness, Bennison, 25 (2017) 63–69

  67. E.M. Jones, C.A. Cochrane, S.L. Percival, The Effect of pH on the Extracellular Matrix and Biofilms. Adv. Wound Care. 4, 431–439 (2015). https://doi.org/10.1089/wound.2014.0538

    Article  Google Scholar 

  68. S.L. Percival, S. McCarty, J.A. Hunt, E.J. Woods, The effects of pH on wound healing, biofilms, and antimicrobial efficacy. Wound Repair. Regen. 22, 174–186 (2014). https://doi.org/10.1111/wrr.12125

    Article  PubMed  Google Scholar 

  69. Y. Hwang, N. Sangaj, S. Varghese, Interconnected macroporous poly(Ethylene Glycol) cryogels as a cell scaffold for cartilage tissue engineering. Tissue Eng. - Part. A 16, 3033–3041 (2010). https://doi.org/10.1089/ten.tea.2010.0045

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Materials Research, Iranian Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch, Mashhad, Iran

    Mahsa Haghbin, Alireza Sadeghi-Avalshahr, Ahmad Moloodi & Zahra Harati

  2. Department of Stem Cell and Regenerative Medicine Research, Iranian Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch, Mashhad, Iran

    Halimeh Hassanzadeh

  3. Department of Mechanical and Materials Engineering, Sadjad University of Technology, Mashhad, Iran

    Mahsa Haghbin & Zahra Harati

  4. Tissue Engineering Research Group (TERG), Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 917794-8564, Iran

    Alireza Sadeghi-Avalshahr

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Haghbin, M., Sadeghi-Avalshahr, A., Hassanzadeh, H. et al. Preparation of porous alginate-based smart dressings used in real-time monitoring of pH in chronic wounds by evaluating two fabrication routes: freeze-drying vs. electrospinning. J Porous Mater 30, 1953–1963 (2023). https://doi.org/10.1007/s10934-023-01477-5

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