Design of Novel 3D-Scaffold as a Potential Material to Induct Epidermal-Dermal Keratinocytes of Human-Adipose-Derived Stem Cells and Promote Fibroblast Cells Proliferation for Skin Regeneration

Abstract

Dermal lesions and chronic wounds associated with burns or some diseases like diabetes are the more important public health concerns which can affect the quality of life. Currently, tissue engineering is considered as the most effective therapeutic method although the design of polymeric substrates for epidermal-dermal differentiation and wound healing (scar-free) is the main challenge. For this purpose, we designed a hybrid three-dimensional scaffold (CPCP) based on collagen/chitosan modified by PEG/PCL composite that can imitate differentiation pattern of both epidermis/dermis cells, via mimicking the structure and function of human skin. The physicochemical, mechanical and biological properties of designed scaffolds were evaluated to study their function for skin tissue engineering applications. Comparison of FTIR analysis showed a chemical similarity between CPCP and decellularized dermal matrix (DDM). Our results showed that combination of two natural/two synthetic polymers led to the formation of stronger 3D-network together with higher modulus (-18), water absorption (4-fold), porosity (-92) and consequently lower pores size (-54 um), compared to natural, synthetic and natural/ synthetic copolymer-based scaffolds. The observation of human skin fibroblast cells proliferation and morphology showed that CPCP was more beneficial to cell adhesion, proliferation, and extension than that of other designed scaffolds due to its hydrophilicity and higher wettability (WCA=60°). According to the results of RT-PCR, the more expression of epidermal-dermal keratinocytes induced by human-adipose-derived stem cells was observed on the CPCP along with a pattern similar to skin. The results demonstrate CPCP can act as a super-absorbent substrate/dressing for continuous absorption of wound exudates. Furthermore, it can potentially be effective for re-epithelialization of skin together with its derivative (hair follicles, sebaceous/sweat glands). This study indicates new insights into the design of skin- engineered scaffolds.

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References

  1. 1.

    A. I. Aghmiuni and A. A. Khiavi in “Aromatic and Medicinal Plants - Back to Nature” (H. A. El-Shemy Ed.), pp.1–28, InTech, Rijeka, https://doi.org/10.5772/67062, 2017.

    Google Scholar 

  2. 2.

    C. Harvey, Orthop. Nurs., 24, 143 (2005).

    PubMed  Google Scholar 

  3. 3.

    A. S. Halim, T. L. Khoo, and S. J. Mohd Yussof, Indian J. Plast. Surg. Off. Publ. Assoc. Plast. Surg. India, 43, S23 (2010).

    Article  Google Scholar 

  4. 4.

    I. Brockmann, J. Ehrenpfordt, T. Sturmheit, M. Brandenburger, C. Kruse, M. Zille, D. Rose, and J. Boltze, Stem Cells Int., 2018, 1 (2018).

    Article  CAS  Google Scholar 

  5. 5.

    O. S. Somuncu, C. Karahan, S. Somuncu, and F. Sahin in “Stem Cells in Clinical Practice and Tissue Engineering”, (R. Sharma Ed.), pp.315–333, IntechOpen, Rijeka, https://doi.org/10.5772/intechopen.69905, 2018.

    Google Scholar 

  6. 6.

    K. Vig, A. Chaudhari, S. Tripathi, S. Dixit, R. Sahu, S. Pillai, V. Dennis, and S. Singh, Int. J. Mol. Sci., 18, 789 (2017).

    PubMed Central  Article  CAS  Google Scholar 

  7. 7.

    N. Bhardwaj, D. Chouhan, and B. B. Mandal, Curr Pharm. Des., 23, 3455 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    C. Pang, A. Ibrahim, N. W. Bulstrode, and P. Ferretti, Int. Wound J., 14, 450 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    N. Sultana in “Functional 3D Tissue Engineering Scaffolds” (Y. Deng and J. Kuiper Eds.), pp.1–21, Woodhead Publishing, http://www.sciencedirect.com/science/article/pii/B978008100979600001X, 2018.

  10. 10.

    V. Andreu, G. Mendoza, M. Arruebo, and S. frusta, Materials (Basel), 8, 5154 (2015).

    Article  Google Scholar 

  11. 11.

    Y. Xu, D. Xia, J. Han, S. Yuan, H. Lin, and C. Zhao, Carbohydr. Polym., doi:https://doi.org/10.1016/j.carbpol.2017.08.069 (2017).

    Google Scholar 

  12. 12.

    F. Khan and S. R. Ahmad, Macromol. Biosci., 13, 395 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    S. Ahmed and S. Ikram, Achiev. Life Sci., 10, 27 (2016).

    Google Scholar 

  14. 14.

    S. Ahmed and M. Ahmad, Immunochem. Immunopathol, 1, 2 (2015).

    Article  Google Scholar 

  15. 15.

    R. Zhao, X. Li, B. Sun, Y. Zhang, D. Zhang, Z. Tang, X. Chen, and C. Wang, Int. J. Biol. Macromol, 68, 92 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    N. Cai, C. Li, C. Han, X. Luo, L. Shen, Y. Xue, and F. Yu, Appl. Surf. Sci., 369, 492 (2016).

    CAS  Article  Google Scholar 

  17. 17.

    M. Mori, S. Rossi, F. Ferrari, M. C. Bonferoni, G. Sandri, T. Chlapanidas, M. L. Torre, and C. Caramella, J. Pharm. Sci, 105, 1180 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    B. H. Leon-Mancilla, M. A. Araiza-Tellez, J. O. Flores-Flores, and M. C. Pina-Barba, J. Appl. Res. Technol, 14, 77 (2016).

    Article  Google Scholar 

  19. 19.

    M. Rodriguez-Vazquez, B. Vega-Ruiz, R. Ramos-Zuniga, D. A. Saldana-Koppel, and L. F. Quinones-Olvera, Biomed Res. Int., 2015, 1 (2015).

    Google Scholar 

  20. 20.

    G. Kim, S. Ann, Y. Kim, Y. Cho, and W. Chun, J. Mater. Chem., 21, 6165 (2011).

    CAS  Article  Google Scholar 

  21. 21.

    L. Ma, C. Gao, Z. Mao, J. Zhou, J. Shen, X. Hu, and C. Han, Biomaterials, 24, 4833 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    C. Tangsadthakun, S. Kanokpanont, N. Sanchavanakit, T. Banaprasert, and S. Damrongsakkul, J. Met. Mater. Miner, 16, 37 (2006).

    CAS  Google Scholar 

  23. 23.

    D. Indrani, F. Lukitowati, and Y Yulizar, IOP Conf. Ser Mater. Sci. Eng, 202, 12020 (2017).

    Article  Google Scholar 

  24. 24.

    V. T. Tchemtchoua, G. Atanasova, A. Aqil, P. Filee, N. Garbacki, O. Vanhooteghem, C. Deroanne, A. Noel, C. Jerome, B. Nusgens, Y. Poumay, and A. Colige, Bio-macromolecules, 12, 3194 (2011).

    CAS  Article  Google Scholar 

  25. 25.

    Y. Yan, X. Zhang, C. Li, Y Huang, Q. Ding, and X. Pang, Appl. Surf. Sci., 332, 62 (2015).

    CAS  Article  Google Scholar 

  26. 26.

    G. BaoLin and P. X. Ma, Sci China. Chem., 57, 490 (2014).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  27. 27.

    B. Dhandayuthapani, Y. Yoshida, T. Maekawa, and D. S. Kumar, Int. J. Polym. Sci, {2011}, doi:https://doi.org/10.1155/2011/290602 (2011).

    Google Scholar 

  28. 28.

    M. Mir, M. N. Ali, A. Barakullah, A. Gulzar, M. Arshad, S. Fatima, and M. Asad, Prog. Biomater, 7, 1 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  29. 29.

    S.-H. Chen, C.-T. Tsao, C.-H. Chang, Y.-T. Lai, M.-F. Wu, C.-N. Chuang, H.-C. Chou, C.-K. Wang, and K.-H. Hsieh, Mater. Sci. Eng. C, 33, 2584 (2013).

    CAS  Article  Google Scholar 

  30. 30.

    S. Eshraghi and S. Das, Acta Biomater, 6, 2467 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    K. T. Shalumon, K. H. Anulekha, K. P. Chennazhi, H. Tamura, S. V Nair, and R. Jayakumar, Int. J. Biol. Macromol., 48, 571 (2011).

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Y. Wu and Y. Han in “Functional 3D Tissue Engineering Scaffolds”, pp.367–390, Elsevier, https://doi.org/10.1016/B978-0-08-100979-6.00014-8, 2017.

    Google Scholar 

  33. 33.

    Z. Fereshteh in “Functional 3D Tissue Engineering Scaffolds” (Y. Deng and J. Kuiper Eds.), pp.151–174, Elsevier, http://www.sciencedirect.com/science/article/pii/B9780081009796000070), 2018.

  34. 34.

    S. P. Huang, C. C. Hsu, S. C. Chang, C. H. Wang, S. C. Deng, N. T. Dai, T. M. Chen, J. Y. H. Chan, S. G Chen, and S. M. Huang, Ann. Plast. Surg, 69, 656 (2012).

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    W. K. Ong and S. Sugii, Int. J. Biochem. Cell Biol., 45, 1083 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  36. 36.

    R. Dai, Z. Wang, R. Samanipour, K. Koo, and K. Kim, Stem Cells Int., 2016, 1 (2016).

    CAS  Google Scholar 

  37. 37.

    L. Frese, P. E. Dijkman, and S. P. Hoerstrup, Transfus. Med. Hemotherapy, 43, 268 (2016).

    Article  Google Scholar 

  38. 38.

    available at https://www.astm.org/DATABASE.CART/HISTORICAL/D3039D3039M-00.htm.

  39. 39.

    U. J. Kim, J. Park, H. Joo Kim, M. Wada, and D. L. Kaplan, Biomaterials, 26, 2775 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    K. K. Nayak and P. Gupta, Int. J. Biol. Macromol, 81, 1 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    S. Miguel, M. Ribeiro, P. Coutinho, and I. Correia, Polymers (Basel), 9, 183 (2017).

    Article  CAS  Google Scholar 

  42. 42.

    S. Heidari Keshel, M. Rostampour, G. Khosropour, B. A. Bandbon, A. Baradaran-Rafii, and E. Biazar, J. Biomater. Sci. Polym. Ed, 27, 339 (2015).

    Article  CAS  Google Scholar 

  43. 43.

    S. S. Sarvandi, M. T. Joghataei, K. Parivar, M. Khosravi, A. Sarveazad, and N. Sanadgol, Ira n. J. Basic Med. Sci, 18, 89 (2015).

    Google Scholar 

  44. 44.

    P. Thevenot, W. Hu, and L. Tang, Curr Top. Med. Chem., 8, 270 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    B. G. Keselowsky, D. M. Collard, and A. J. Garcia, J. Biomed. Mater. Res. A, 66, 247 (2003).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  46. 46.

    T. Riaz, R. Zeeshan, F. Zarif, K. Ilyas, N. Muhammad, S. Z. Safi, A. Rahim, S. A. A. Rizvi, and I. U. Rehman, Appl. Spectrosc. Rev., 53, 703 (2018).

    CAS  Article  Google Scholar 

  47. 47.

    F. Selmin, F. Cilurzo, A. Aluigi, S. Franze, and P. Minghetti, Results PharmaSci, 2, 72 (2012).

    Article  Google Scholar 

  48. 48.

    D. M. Mackie in Sensing Technologies for Global Health, Military Medicine, Disaster Response, and Environmental Monitoring II; and Biometric Technology for Human Identification IX, Vol. 8371, pp.83711T-83711T-8 (2012).

  49. 49.

    G. Ahn, K. H. Min, C. Kim, J. S. Lee, D. Kang, J. Y. Won, D. W. Cho, J. Y. Kim, S. Jin, W. S. Yun, and J. H. Shim, Sci. Rep., 7, I (2017).

    Google Scholar 

  50. 50.

    N. I. Afanasyeva, Macromol. Symp., 141, 117 (1999).

    CAS  Article  Google Scholar 

  51. 51.

    P. B. Milan, N. Lotfibakhshaiesh, M. T. Joghataie, J. Ai, A. Pazouki, D. L. Kaplan, S. Kargozar, N. Amini, M. R. Hamblin, M. Mozafari, and A. Samadikuchaksaraei, Acta Biomater, 45, 234 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    C. M. Healy and J. G. Boorman, Burns. Inch Therm. Inj., 15, 52 (1989).

    CAS  Article  Google Scholar 

  53. 53.

    T. M. MacLeod, A. Cambrey, G. Williams, R. Sanders, and C. J. Green, Burns, 34, 1169 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    M. Vitacolonna, M. Mularczyk, F. Herrle, T. J. Schulze, H. Haupt, M. Oechsner, L. R. Pilz, P. Hohenberger, and E. D. Rossner, BMC Surg., 14, 7 (2014).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  55. 55.

    H.-I. Chang and Y. Wang in “Regenerative Medicine and Tissue Engineering - Cells and Biomaterials”, Vol. 2, p.64, http://www.intechopen.com/books/genetic-engineering-basics-new-applications-and-responsibilities/gateway-vectors-for-plant-genetic-engineering-overview-of-plant-vectors-application-for-bimolecular-), InTech, 2011.

    Google Scholar 

  56. 56.

    S. Moeini, M. R. Mohammadi, and A. Simchi, Bioact. Mater, 2, 146 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    J. M. Goddard and J. H. Hotchkiss, Prog. Polym. Sci, 32, 698 (2007).

    CAS  Article  Google Scholar 

  58. 58.

    L.-C. Xu and C. A. Siedlecki, Biomaterials, 28, 3273 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    T. Snape, Astles. Alison, J. Davies, A. Astles, and J. Davies, Pharm. J., 385, 416 (2010).

    Google Scholar 

  60. 60.

    S. H. Keshel, M. Soleimani, M. R. Tavirani, M. Ebrahimi, R. Raeisossadati, H. Yasaei, D. Afsharzadeh, M. J. Behroz, A. Atashi, S. Amanpour, A. Khoshzaban, R. Roozafzoon, and G R. Behrouzi, Mol. Reprod. Dev., 79, 709 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    M. Kim and G. Kim, RSCAdv., 5, 26954 (2015).

    CAS  Google Scholar 

  62. 62.

    D. E. Lopez Angulo and P. J. do Amaral Sobral, Int. J. Biol. Macromol., 92, 645 (2016).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  63. 63.

    T. W. Wang, H. C. Wu, Y. C. Huang, J. S. Sun, and F. H. Lin, Artif. Organs, 30, 141 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  64. 64.

    E. Sachlos, J. T. Czernuszka, S. Gogolewski, and M. Dalby, Eur. Cells Mater, 5, 29 (2003).

    CAS  Article  Google Scholar 

  65. 65.

    X. Zhu, W. Cui, X. Li, and Y. Jin, Biomacromolecules, 9, 1795 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  66. 66.

    D. Atila, D. Keskin, and A. Tezcaner, Carbohydr. Polym., 133,251(2015).

  67. 67.

    F. J. O’Brien, B. A. Harley, I. V. Yannas, and L. J. Gibson, Biomaterials, 26, 433 (2005).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  68. 68.

    J. Ma, H. Wang, B. He, and J. Chen, Biomaterials, 22, 331 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  69. 69.

    W. F. Lee and Y. J. Chen, J. Appl. Polym. Sci., 82, 2487 (2001).

    CAS  Article  Google Scholar 

  70. 70.

    J. Yang, G. Shi, J. Bei, S. Wang, Y. Cao, Q. Shang, G. Yang, and W. Wang, J. Biomed. Mater. Res., 62, 438 (2002).

    CAS  PubMed  Article  Google Scholar 

  71. 71.

    H.-I. Chang and Y. Wang in Regenerative Medicine and Tissue Engineering - Cells and Biomaterials, 2011.

    Google Scholar 

  72. 72.

    J. Wei, T. Igarashi, N. Okumori, T. Igarashi, T. Maetani, B. Liu, and M. Yoshinari, Biomed. Mater, 4, 45002 (2009).

    Article  CAS  Google Scholar 

  73. 73.

    D. Dowling, I. Miller, M. Ardhaoui, and W Gallagher, J. Biomater. Appl, 26, 327 (2011).

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    E. D. Yildirim, R. Besunder, D. Pappas, F. Allen, S. Giiceri, and W Sun, Biofabrication, 2, 14109 (2010).

    Article  CAS  Google Scholar 

  75. 75.

    C. Reshmi, P. Suja, O. Manaf, P. Sanu, and A. Sujith, Int. J. Biol. Macromol, 108, 1261 (2018).

    Article  CAS  Google Scholar 

  76. 76.

    R. Moll, M. Divo, and L. Langbein, Histochem. Cell Biol, 129, 705 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    L. Cassimeris, G. Plopper, and V. R. Lingappa, “Lewin’s CELLS”, Jones & Bartlett Learning, LLC, 2011; https://books.google.com/books?id=wHxomxPuWYkC.

    Google Scholar 

  78. 78.

    G. Guasch, Biol. Eng Stem Cell Niches, 127–143 (2017).

    Google Scholar 

  79. 79.

    A. M. B. Tadeu and V. Horsley, “Epithelial Stem Cells in Adult Skin”, Vol. 107, https://doi.org/10.1016/B978-0-12-416022-4.00004-4), Elsevier Inc., ed. 1, 2014.

    Google Scholar 

  80. 80.

    E. B. Lane and W. H. I. McLean, J. Pathol, 204, 355 (2004).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

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Acknowledgments

We would like to express our deep appreciation to Dr. Arash Sarveazad for all his guidance that has given us over the past three years.

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Correspondence to Mazyar Sharifzadeh Baei.

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Aghmiuni, A.I., Baei, M.S., Keshel, S.H. et al. Design of Novel 3D-Scaffold as a Potential Material to Induct Epidermal-Dermal Keratinocytes of Human-Adipose-Derived Stem Cells and Promote Fibroblast Cells Proliferation for Skin Regeneration. Fibers Polym 21, 33–44 (2020). https://doi.org/10.1007/s12221-020-9402-1

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Keywords

  • Wound healing
  • Skin tissue engineering
  • Natural polymer
  • Epidermal-dermal keratinocytes
  • Extracellular matrix (ECM) structure