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Combination Therapy of Stem Cell-derived Exosomes and Biomaterials in the Wound Healing

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Abstract

Wound healing is a serious obstacle due to the complexity of evaluation and management. While novel approaches to promoting chronic wound healing are of critical interest at the moment, several studies have demonstrated that combination therapy is critical for the treatment of a variety of diseases, particularly chronic wounds. Among the various approaches that have been proposed for wound care, regenerative medicine-based methods have garnered the most attention. As is well known, regenerative medicine’s three primary tools are gene/cell therapy, biomaterials, and tissue engineering. Multifunctional biomaterials composed of synthetic and natural components are highly advantageous for exosome carriers, which utilizing them is an exciting wound healing method. Recently, stem cell-secreted exosomes and certain biomaterials have been identified as critical components of the wound healing process, and their combination therapy appears to produce significant results. This paper presents a review of literature and perspectives on the use of stem cell-derived exosomes and biomaterials in wound healing, particularly chronic wounds, and discusses the possibility of future clinical applications.

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References

  1. Hamblin, M. R., Avci, P., & Prow, T. W. (2016). Nanoscience in dermatology. Nanoscience in Dermatology, 1–390. https://doi.org/10.1016/C2014-0-03862-2

  2. Han, G., & Ceilley, R. (2017). Chronic wound healing: a review of current management and treatments. Advances in Therapy, 34(3), 599–610. https://doi.org/10.1007/S12325-017-0478-Y

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chen, D., Hou, Q., Zhong, L., Zhao, Y., Li, M., & Fu, X. (2019). Bioactive molecules for skin repair and regeneration: progress and perspectives. Stem Cells International, 2019. https://doi.org/10.1155/2019/6789823

  4. Zhou, Y., Zhang, X. L., Zhang, H. J., Lu, Y. J., Zhao, B., Zhang, N. Y., & Zhang, J. (2021). Human adipose-derived mesenchymal stem cells-derived exosomes encapsulated in pluronic F127 hydrogel promote wound healing and regeneration. https://doi.org/10.21203/rs.3.rs-670650/v1

  5. Percival, N. J. (2002). Classification of wounds and their management. Surgery (Oxford), 20(5), 114–117. https://doi.org/10.1383/SURG.20.5.114.14626

    Article  Google Scholar 

  6. Shi, J., Ma, X., Su, Y., Song, S., Tian, Y., Yuan, Y., et al. (2018). MiR-31 mediates inflammatory signaling to promote re-epithelialization during skin wound healing. The Journal of Investigative Dermatology, 138(10), 2253–2263. https://doi.org/10.1016/J.JID.2018.03.1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Golchin, A., Hosseinzadeh, S., Jouybar, A., Staji, M., Soleimani, M., Ardeshirylajimi, A., & Khojasteh, A. (2020). Wound healing improvement by curcumin-loaded electrospun nanofibers and BFP-MSCs as a bioactive dressing. Polymers for Advanced Technologies, 31(7), https://doi.org/10.1002/pat.4881

  8. Rousselle, P., Braye, F., & Dayan, G. (2019). Re-epithelialization of adult skin wounds: Cellular mechanisms and therapeutic strategies. Advanced Drug Delivery Reviews, 146, 344–365. https://doi.org/10.1016/J.ADDR.2018.06.019

    Article  CAS  PubMed  Google Scholar 

  9. Goodarzi, P., Larijani, B., Alavi-Moghadam, S., Tayanloo-Beik, A., Mohamadi-Jahani, F., Ranjbaran, N., et al. (2018). Mesenchymal stem cells-derived exosomes for wound regeneration. Advances in Experimental Medicine and Biology, 1119, 119–131. https://doi.org/10.1007/5584_2018_251

    Article  CAS  PubMed  Google Scholar 

  10. Cha, H., Hong, S., Park, J. H., & Park, H. H. (2020). Stem cell-derived exosomes and nanovesicles: promotion of cell proliferation, migration, and anti-senescence for treatment of wound damage and skin ageing. Pharmaceutics, 12(12), 1135. https://doi.org/10.3390/PHARMACEUTICS12121135

    Article  CAS  PubMed Central  Google Scholar 

  11. Basiri, A., Mansouri, F., Azari, A., Ranjbarvan, P., Zarein, F., Heidari, A., & Golchin, A. (2021). Stem cell therapy potency in personalizing severe COVID-19 treatment. Stem Cell Reviews and Reports, 17, 193–213. Springer. https://doi.org/10.1007/s12015-020-10110-w

  12. Zhang, Y., Liu, Y., Liu, H., & Tang, W. H. (2019). Exosomes: biogenesis, biologic function and clinical potential. Cell & Bioscience 9(1), 1–18. https://doi.org/10.1186/S13578-019-0282-2

  13. Li, X., Corbett, A. L., Taatizadeh, E., Tasnim, N., Little, J. P., Garnis, C., et al. (2019). Challenges and opportunities in exosome research—Perspectives from biology, engineering, and cancer therapy. APL Bioengineering, 3(1), 11503. https://doi.org/10.1063/1.5087122

    Article  CAS  Google Scholar 

  14. Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature Biotechnology, 29(4), 341–345. https://doi.org/10.1038/nbt.1807

    Article  CAS  PubMed  Google Scholar 

  15. Doyle, L. M., & Wang, M. Z. (2019). Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells, 8(7), 727. https://doi.org/10.3390/CELLS8070727

    Article  CAS  PubMed Central  Google Scholar 

  16. Álvarez-Viejo, M. (2020). Mesenchymal stem cells from different sources and their derived exosomes: a pre-clinical perspective. World Journal of Stem Cells, 12(2), 100

    Article  PubMed  PubMed Central  Google Scholar 

  17. Pols, M. S., & Klumperman, J. (2009). Trafficking and function of the tetraspanin CD63. Experimental Cell Research, 315(9), 1584–1592

    Article  CAS  PubMed  Google Scholar 

  18. Ding, R., Jiang, X., Ha, Y., Wang, Z., Guo, J., Jiang, H., et al. (2015). Activation of Notch1 signalling promotes multi-lineage differentiation of c-KitPOS/NKX2.5POS bone marrow stem cells: implication in stem cell translational medicine. Stem Cell Research & Therapy, 6(1), https://doi.org/10.1186/S13287-015-0085-2

  19. Shi, H. X., Lin, C., Lin, B. B., Wang, Z. G., Zhang, H. Y., Wu, F. Z., et al. (2013). The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. PLoS One, 8(4), e59966. https://doi.org/10.1371/JOURNAL.PONE.0059966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Xie, M., Wu, D., Li, G., Yang, J., & Zhang, Y. S. (2021). Exosomes targeted towards applications in regenerative medicine. Nano Select, 2(5), 880–908. https://doi.org/10.1002/NANO.202000251

    Article  CAS  Google Scholar 

  21. Wang, X., Rivera-Bolanos, N., Jiang, B., & Ameer, G. A. (2019). Advanced functional biomaterials for stem cell delivery in regenerative engineering and medicine. Advanced Functional Materials, 29(23), 1809009. https://doi.org/10.1002/ADFM.201809009

    Article  Google Scholar 

  22. Golchin, A., Farzaneh, S., Porjabbar, B., Sadegian, F., Estaji, M., Ranjbarvan, P., et al. (2020). Regenerative medicine under the control of 3D scaffolds: current state and progress of tissue scaffolds. Current Stem Cell Research & Therapy, 16(2), 209–229. https://doi.org/10.2174/1574888X15666200720115519

    Article  Google Scholar 

  23. Werner, S., & Grose, R. (2003). Regulation of wound healing by growth factors and cytokines. Physiological Reviews, 83(3), 835–870. https://doi.org/10.1152/PHYSREV.2003.83.3.835

    Article  CAS  PubMed  Google Scholar 

  24. Steed, D. L. (1995). Clinical evaluation of recombinant human platelet–derived growth factor for the treatment of lower extremity diabetic ulcers. Journal of Vascular Surgery, 21(1), 71–81. https://doi.org/10.1016/S0741-5214(95)70245-8

    Article  CAS  PubMed  Google Scholar 

  25. Grazul-Bilska, A. T., Johnson, M. L., Bilski, J. J., Redmer, D. A., Reynolds, L. P., Abdullah, A., & Abdullah, K. M. (2003). Wound healing: the role of growth factors. Drugs of Today (Barcelona, Spain: 1998), 39(10), 787–800. https://doi.org/10.1358/DOT.2003.39.10.799472

    Article  CAS  Google Scholar 

  26. Pang, C., Ibrahim, A., Bulstrode, N. W., & Ferretti, P. (2017). An overview of the therapeutic potential of regenerative medicine in cutaneous wound healing. International Wound Journal, 14(3), 450–459. https://doi.org/10.1111/IWJ.12735

    Article  PubMed  PubMed Central  Google Scholar 

  27. Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H., & Tomic-Canic, M. (2008). Growth factors and cytokines in wound healing. Wound Repair and Regeneration : Official Publication of The Wound Healing Society [and] The European Tissue Repair Society, 16(5), 585–601. https://doi.org/10.1111/J.1524-475X.2008.00410.X

    Article  Google Scholar 

  28. Yao, C., Yao, P., Wu, H., & Zha, Z. (2006). Acceleration of wound healing in traumatic ulcers by absorbable collagen sponge containing recombinant basic fibroblast growth factor. Biomedical Materials (Bristol, England), 1(1), 33–37. https://doi.org/10.1088/1748-6041/1/1/005

    Article  CAS  Google Scholar 

  29. Borena, B. M., Martens, A., Broeckx, S. Y., Meyer, E., Chiers, K., Duchateau, L., & Spaas, J. H. (2015). Regenerative skin wound healing in mammals: state-of-the-art on growth factor and stem cell based treatments. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 36(1), 1–23. https://doi.org/10.1159/000374049

    Article  CAS  Google Scholar 

  30. Shi, H. X., Lin, C., Lin, B. B., Wang, Z. G., Zhang, H. Y., Wu, F. Z., et al. (2013). The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. PLoS One, 8(4). https://doi.org/10.1371/JOURNAL.PONE.0059966

  31. Finnson, K. W., Arany, P. R., & Philip, A. (2013). Transforming growth factor beta signaling in cutaneous wound healing: lessons learned from animal studies. Advances in Wound Care, 2(5), 225–237. https://doi.org/10.1089/WOUND.2012.0419

    Article  PubMed  PubMed Central  Google Scholar 

  32. Katsuno, Y., & Derynck, R. (2021). Epithelial plasticity, epithelial-mesenchymal transition, and the TGF-β family. Developmental Cell, 56(6), 726–746. https://doi.org/10.1016/J.DEVCEL.2021.02.028

    Article  CAS  PubMed  Google Scholar 

  33. Chen, L., Tredget, E. E., Wu, P. Y. G., & Wu, Y. (2008). Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One, 3(4), e1886. https://doi.org/10.1371/JOURNAL.PONE.0001886

    Article  PubMed  PubMed Central  Google Scholar 

  34. Leahy, P. J., & Lawrence, W. T. (2007). Biologic enhancement of wound healing. Clinics in Plastic Surgery, 34(4), 659–671. https://doi.org/10.1016/J.CPS.2007.07.001

    Article  PubMed  Google Scholar 

  35. Golchin, A., & Nourani, M. R. (2020). Effects of bilayer nanofibrillar scaffolds containing epidermal growth factor on full-thickness wound healing. Polymers for Advanced Technologies, 31(11). https://doi.org/10.1002/pat.4960

  36. Ranjbarvan, P., Golchin, A., Azari, A., & Niknam, Z. (2021). The bilayer skin substitute based on human adipose-derived mesenchymal stem cells and neonate keratinocytes on the 3D nanofibrous PCL-platelet gel scaffold. Polymer Bulletin, 1–18. https://doi.org/10.1007/s00289-021-03702-0

  37. Golchin, A., Hosseinzadeh, S., & Roshangar, L. (2018). The role of nanomaterials in cell delivery systems. Medical Molecular Morphology, 51(1), https://doi.org/10.1007/s00795-017-0173-8

  38. Kallis, P. J., Friedman, A. J., & Lev-Tov, H. (2018). A Guide to Tissue-Engineered Skin Substitutes. Journal of Drugs in Dermatology, 17(1), 57–64

    PubMed  Google Scholar 

  39. Mansbridge, J. N. (2013). Chapter II.6.12 - Tissue-Engineered Skin Substitutes. In B. D. Ratner, A. S. Hoffman, F. J. Schoen, & J. E. Lemons (Eds.), Biomaterials Science (3rd Edn., pp. 1276–1288). Academic. https://doi.org/10.1016/B978-0-08-087780-8.00119-4

  40. Tottoli, E. M., Dorati, R., Genta, I., Chiesa, E., Pisani, S., & Conti, B. (2020). Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics, 12(8), 735

    Article  CAS  PubMed Central  Google Scholar 

  41. Nour, S., Imani, R., Chaudhry, G. R., & Sharifi, A. M. (2021). Skin wound healing assisted by angiogenic targeted tissue engineering: A comprehensive review of bioengineered approaches. Journal of Biomedical Materials Research Part A, 109(4), 453–478

    Article  CAS  PubMed  Google Scholar 

  42. Masuda, S., Shimizu, T., Yamato, M., & Okano, T. (2008). Cell sheet engineering for heart tissue repair. Advanced Drug Delivery Reviews, 60(2), 277–285

    Article  CAS  PubMed  Google Scholar 

  43. Theoret, C. (2009). Tissue engineering in wound repair: the three “R” s—repair, replace, regenerate. Veterinary Surgery, 38(8), 905–913

    Article  PubMed  Google Scholar 

  44. Hilmi, A. B. M., & Halim, A. S. (2015). Vital roles of stem cells and biomaterials in skin tissue engineering. World Journal of Stem Cells, 7(2), 428

    Article  Google Scholar 

  45. Stark, H. J., Boehnke, K., Mirancea, N., Willhauck, M. J., Pavesio, A., Fusenig, N. E., & Boukamp, P. (2006). Epidermal homeostasis in long-term scaffold-enforced skin equivalents. In Journal of Investigative Dermatology Symposium Proceedings (Vol. 11, pp. 93–105). Elsevier

  46. Hashemi, S., Amirabad, L. M., Nazhvani, F. D., Zarrintaj, P., Namazi, H., Saadatfar, A., & Golchin, A. (2021). Bilayer scaffolds for interface tissue engineering and regenerative medicine: a systematic reviews. Advances in Experimental Medicine and Biology (pp. 1–31). Springer. https://doi.org/10.1007/5584_2021_637

  47. Golchin, A., & Farahany, T. Z. (2019). Biological products: cellular therapy and FDA approved products. Stem Cell Reviews and Reports, 15(2), 1–10. https://doi.org/10.1007/s12015-018-9866-1

    Article  Google Scholar 

  48. Dreifke, M. B., Jayasuriya, A. A., & Jayasuriya, A. C. (2015). Current wound healing procedures and potential care. Materials Science and Engineering: C, 48, 651–662

    Article  CAS  Google Scholar 

  49. Kucharzewski, M., Rojczyk, E., Wilemska-Kucharzewska, K., Wilk, R., Hudecki, J., & Los, M. J. (2019). Novel trends in application of stem cells in skin wound healing. European Journal of Pharmacology, 843, 307–315. https://doi.org/10.1016/J.EJPHAR.2018.12.012

    Article  CAS  PubMed  Google Scholar 

  50. Sahoo, S., & Losordo, D. W. (2014). Exosomes and cardiac repair after myocardial infarction. Circulation Research, 114(2), 333–344

    Article  CAS  PubMed  Google Scholar 

  51. Tao, H., Han, Z., Han, Z. C., & Li, Z. (2016). Proangiogenic features of mesenchymal stem cells and their therapeutic applications. Stem Cells International 1314709. https://doi.org/10.1155/2016/1314709

  52. Zhao, X., Cui, K., & Li, Z. (2019). The role of biomaterials in stem cell-based regenerative medicine. Future Medicinal Chemistry, 11(14), 1777–1790

    Article  CAS  PubMed  Google Scholar 

  53. Phinney, D. G., & Pittenger, M. F. (2017). Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells, 35(4), 851–858. https://doi.org/10.1002/stem.2575

    Article  CAS  PubMed  Google Scholar 

  54. Li, X., Liu, L., Yang, J., Yu, Y., Chai, J., Wang, L., et al. (2016). Exosome derived from human umbilical cord mesenchymal stem cell mediates MiR-181c attenuating burn-induced excessive inflammation. EBioMedicine, 8, 72–82. https://doi.org/10.1016/J.EBIOM.2016.04.030

    Article  PubMed  PubMed Central  Google Scholar 

  55. Yang, J., Chen, Z., Pan, D., Li, H., & Shen, J. (2020). Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration. International Journal of Nanomedicine, 15, 5911. https://doi.org/10.2147/IJN.S249129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hu, L. I., Wang, J., Zhou, X., Xiong, Z., Zhao, J., Yu, R., et al. (2016). Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Scientific Reports, 6(1), 1–11. https://doi.org/10.1038/srep32993

    Article  CAS  Google Scholar 

  57. Qiu, X., Liu, J., Zheng, C., Su, Y., Bao, L., Zhu, B., et al. (2020). Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis. Cell Proliferation, 53(8), e12830

  58. Kim, S., Lee, S. K., Kim, H., & Kim, T. M. (2018). Exosomes secreted from induced pluripotent stem cell-derived mesenchymal stem cells accelerate skin cell proliferation. International Journal of Molecular Sciences, 19(10), 3119. https://doi.org/10.3390/IJMS19103119

    Article  PubMed Central  Google Scholar 

  59. Zhao, G., Liu, F., Liu, Z., Zuo, K., Wang, B., Zhang, Y., et al. (2020). MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing. Stem Cell Research & Therapy, 11(1), 1–18. https://doi.org/10.1186/S13287-020-01616-8

    Article  Google Scholar 

  60. Shi, Q., Qian, Z., Liu, D., Sun, J., Wang, X., Liu, H., et al. (2017). GMSC-derived exosomes combined with a chitosan/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model. Frontiers in Physiology, 8(NOV), 904. https://doi.org/10.3389/FPHYS.2017.00904

    Article  PubMed  PubMed Central  Google Scholar 

  61. Kim, Y. J., Yoo, S. M., Park, H. H., Lim, H. J., Kim, Y. L., Lee, S., et al. (2017). Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin. Biochemical and Biophysical Research Communications, 493(2), 1102–1108. https://doi.org/10.1016/J.BBRC.2017.09.056

    Article  CAS  PubMed  Google Scholar 

  62. Siddesh, S. E., Gowda, D. M., Jain, R., Gulati, A., Patil, G. S., Anudeep, T. C., et al. (2021). Placenta-derived mesenchymal stem cells (P-MSCs) for COVID-19 pneumonia-a regenerative dogma. Stem Cell Investigation, 8, 3. https://doi.org/10.21037/sci-2020-034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gholizadeh-Ghaleh Aziz, S., Pashaei-Asl, F., Fardyazar, Z., & Pashaiasl, M. (2016). Isolation, characterization, cryopreservation of human amniotic stem cells and differentiation to osteogenic and adipogenic cells. PLoS One, 11(7), e0158281

  64. Yang, J., Chen, Z., Pan, D., Li, H., & Shen, J. (2020). Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 Hydrogel promote chronic diabetic wound healing and complete skin regeneration. International Journal of Nanomedicine, 15, 5911–5926. https://doi.org/10.2147/IJN.S249129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ranjbaran, H., Abediankenari, S., Mohammadi, M., Jafari, N., Khalilian, A., Rahmani, Z., et al. (2018). Wharton’s jelly derived-mesenchymal stem cells: isolation and characterization. Acta Medica Iranica, 56(1), 28–33

    PubMed  Google Scholar 

  66. Damania, A., Jaiman, D., Teotia, A. K., & Kumar, A. (2018). Mesenchymal stromal cell-derived exosome-rich fractionated secretome confers a hepatoprotective effect in liver injury. Stem Cell Research & Therapy, 9(1), 1–12

    Article  CAS  Google Scholar 

  67. Ma, H., Lam, P. K., Siu, W. S., Tong, C. S. W., Lo, K. K. Y., Koon, C. M., et al. (2021). Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and ADMSC-Derived Secretome Expedited Wound Healing in a Rodent Model–A preliminary study. Clinical, Cosmetic and Investigational Dermatology, 14, 753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Martínez-Sarrà, E., Montori, S., Gil-Recio, C., Núñez-Toldrà, R., Costamagna, D., Rotini, A., et al. (2017). Human dental pulp pluripotent-like stem cells promote wound healing and muscle regeneration. Stem Cell Research & Therapy, 8(1), 1–20

    Article  CAS  Google Scholar 

  69. Sondergaard, C. S., Hodonsky, C. J., Khait, L., Shaw, J., Sarkar, B., Birla, R., et al. (2010). Human thymus mesenchymal stromal cells augment force production in self-organized cardiac tissue. The Annals of Thoracic Surgery, 90(3), 796–804. https://doi.org/10.1016/j.athoracsur.2010.04.080

    Article  PubMed  PubMed Central  Google Scholar 

  70. Krampera, M., Sartoris, S., Liotta, F., Pasini, A., Angeli, R., Cosmi, L., et al. (2007). Immune regulation by mesenchymal stem cells derived from adult spleen and thymus. Stem Cells and Development, 16(5), 797–810

    Article  CAS  PubMed  Google Scholar 

  71. Sveiven, S. N., & Nordgren, T. M. (2020). Lung-resident mesenchymal stromal cells are tissue-specific regulators of lung homeostasis. American Journal of Physiology-Lung Cellular and Molecular Physiology, 319(2), L197–L210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kholodenko, I. V., Kurbatov, L. V., Kholodenko, R. V., Manukyan, G. V., & Yarygin, K. N. (2019). Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope? Cells, 8(10). https://doi.org/10.3390/CELLS8101127

  73. Chen, J., Park, H. C., Addabbo, F., Ni, J., Pelger, E., Li, H., et al. (2008). Kidney-derived mesenchymal stem cells contribute to vasculogenesis, angiogenesis and endothelial repair. Kidney International, 74(7), 879–889. https://doi.org/10.1038/ki.2008.304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Pombero, A., Garcia-Lopez, R., & Martinez, S. (2016). Brain mesenchymal stem cells: physiology and pathological implications. Development, Growth & Differentiation, 58(5), 469–480

    Article  Google Scholar 

  75. Andrzejewska, A., Lukomska, B., & Janowski, M. (2019). Concise review: mesenchymal stem cells: from roots to boost. Stem Cells, 37(7), 855–864

    Article  PubMed  Google Scholar 

  76. Luo, G., Cheng, W., He, W., Wang, X., Tan, J., Fitzgerald, M., et al. (2010). Promotion of cutaneous wound healing by local application of mesenchymal stem cells derived from human umbilical cord blood. Wound Repair and Regeneration, 18(5), 506–513

    Article  PubMed  Google Scholar 

  77. Liu, X., Yang, Y., Li, Y., Niu, X., Zhao, B., Wang, Y., et al. (2017). Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale, 9, 4430–4438. https://doi.org/10.1039/C7NR00352H

    Article  CAS  PubMed  Google Scholar 

  78. Smith, A. N., Willis, E., Chan, V. T., Muffley, L. A., Isik, F. F., Gibran, N. S., & Hocking, A. M. (2010). Mesenchymal stem cells induce dermal fibroblast responses to injury. Experimental Cell Research, 316(1), 48–54

    Article  CAS  PubMed  Google Scholar 

  79. Tong, C., Hao, H., Xia, L., Liu, J., Ti, D., Dong, L., et al. (2016). Hypoxia pretreatment of bone marrow—derived mesenchymal stem cells seeded in a collagen-chitosan sponge scaffold promotes skin wound healing in diabetic rats with hindlimb ischemia. Wound Repair and Regeneration, 24(1), 45–56

    Article  PubMed  Google Scholar 

  80. Merino-González, C., Zuñiga, F. A., Escudero, C., Ormazabal, V., Reyes, C., Nova-Lamperti, E., et al. (2016). Mesenchymal stem cell-derived extracellular vesicles promote angiogenesis: potencial clinical application. Frontiers in Physiology, 7, 24

    Article  PubMed  PubMed Central  Google Scholar 

  81. Golchin, A., Hosseinzadeh, S., & Ardeshirylajimi, A. (2018). The exosomes released from different cell types and their effects in wound healing. Journal of Cellular Biochemistry, 119(7), 5043–5052. https://doi.org/10.1002/JCB.26706

    Article  CAS  PubMed  Google Scholar 

  82. Li, P., Kaslan, M., Lee, S. H., Yao, J., & Gao, Z. (2017). Progress in exosome isolation techniques. Theranostics, 7(3), 789. https://doi.org/10.7150/THNO.18133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Lee, Y., Andaloussi, E., & Wood, S. (2012). Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Human Molecular Genetics, 21(R1), R125–R134

    Article  CAS  PubMed  Google Scholar 

  84. Golchin, A. (2021). Cell-based therapy for severe COVID-19 patients: clinical trials and cost-utility. Stem Cell Reviews and Reports, 17(1), 56–62. https://doi.org/10.1007/s12015-020-10046-1

    Article  CAS  PubMed  Google Scholar 

  85. Picca, A., Guerra, F., Calvani, R., Coelho-Júnior, H. J., Landi, F., Bernabei, R., et al. (2020). Extracellular vesicles and damage-associated molecular patterns: a Pandora’s box in health and disease. Frontiers in Immunology, 11(2993), https://doi.org/10.3389/fimmu.2020.601740

  86. Yang, G. H., Lee, Y. B., Kang, D., Choi, E., Nam, Y., Lee, K. H., et al. (2021). Overcome the barriers of the skin: exosome therapy. Biomaterials Research, 25(1), 1–13. https://doi.org/10.1186/S40824-021-00224-8

    Article  Google Scholar 

  87. Silachev, D. N., Goryunov, K. V., Shpilyuk, M. A., Beznoschenko, O. S., Morozova, N. Y., Kraevaya, E. E., et al. (2019). Effect of MSCs and MSC-derived extracellular vesicles on human blood coagulation. Cells, 8(3), 258. https://doi.org/10.3390/cells8030258

    Article  CAS  PubMed Central  Google Scholar 

  88. Zeng, Q. L., & Liu, D. W. (2021). Mesenchymal stem cell-derived exosomes: An emerging therapeutic strategy for normal and chronic wound healing. World Journal of Clinical Cases, 9(22), 6218–6233. https://doi.org/10.12998/WJCC.V9.I22.6218, http://www.wjgnet.com/

  89. He, X., Dong, Z., Cao, Y., Wang, H., Liu, S., Liao, L., et al. (2019). MSC-derived exosome promotes M2 polarization and enhances cutaneous wound healing. Stem Cells International 7132708. https://doi.org/10.1155/2019/7132708

  90. Liang, X., Zhang, L., Wang, S., Han, Q., & Zhao, R. C. (2016). Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. Journal of Cell Science, 129(11), 2182–2189. https://doi.org/10.1242/jcs.170373

    Article  CAS  PubMed  Google Scholar 

  91. Fish, J. E., Santoro, M. M., Morton, S. U., Yu, S., Yeh, R. F., Wythe, J. D., et al. (2008). miR-126 regulates angiogenic signaling and vascular integrity. Developmental Cell, 15(2), 272–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. van Balkom, B. W. M., De Jong, O. G., Smits, M., Brummelman, J., den Ouden, K., de Bree, P. M., et al. (2013). Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood, The Journal of the American Society of Hematology, 121(19), 3997–4006

    Google Scholar 

  93. Yang, K., Li, D., Wang, M., Xu, Z., Chen, X., Liu, Q., et al. (2019). Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells. Stem Cell Research & Therapy, 10(1), 1–14

    Article  CAS  Google Scholar 

  94. Ding, J., Wang, X., Chen, B., Zhang, J., & Xu, J. (2019). Exosomes derived from human bone marrow mesenchymal stem cells stimulated by deferoxamine accelerate cutaneous wound healing by promoting angiogenesis. BioMed Research International. https://doi.org/10.1155/2019/9742765

  95. Wang, T., Feng, Y., Sun, H., Zhang, L., Hao, L., Shi, C., et al. (2012). miR-21 regulates skin wound healing by targeting multiple aspects of the healing process. The American Journal of Pathology, 181(6), 1911–1920

    Article  PubMed  Google Scholar 

  96. Roy, S., Santra, S., Das, A., Dixith, S., Sinha, M., Ghatak, S., et al. (2020). Staphylococcus aureus biofilm infection compromises wound healing by causing deficiencies in granulation tissue collagen. Annals of Surgery, 271(6), 1174

    Article  PubMed  Google Scholar 

  97. Jiang, T., Wang, Z., & Sun, J. (2020). Human bone marrow mesenchymal stem cell-derived exosomes stimulate cutaneous wound healing mediates through TGF-β/Smad signaling pathway. Stem Cell Research & Therapy, 11, 1–10

    Article  CAS  Google Scholar 

  98. Liu, K., Chen, C., Zhang, H., Chen, Y., & Zhou, S. (2019). Adipose stem cell-derived exosomes in combination with hyaluronic acid accelerate wound healing through enhancing re‐epithelialization and vascularization. British Journal of Dermatology, 181(4), 854–856

    Article  CAS  PubMed  Google Scholar 

  99. Zhang, W., Bai, X., Zhao, B., Li, Y., Zhang, Y., Li, Z., et al. (2018). Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway. Experimental Cell Research, 370(2), 333–342

    Article  CAS  PubMed  Google Scholar 

  100. Shen, T., Zheng, Q. Q., Shen, J., Li, Q. S., Song, X. H., Luo, H. B., et al. (2018). Effects of adipose-derived mesenchymal stem cell exosomes on corneal stromal fibroblast viability and extracellular matrix synthesis. Chinese Medical Journal, 131(6), 704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Zhang, B., Wu, X., Zhang, X., Sun, Y., Yan, Y., Shi, H., et al. (2015). Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway. Stem Cells Translational Medicine, 4(5), 513–522. https://doi.org/10.5966/sctm.2014-0267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Redman, C. W., & Sargent, I. L. (2000). Placental debris, oxidative stress and pre-eclampsia. Placenta, 21(7), 597–602. https://doi.org/10.1053/PLAC.2000.0560

    Article  CAS  PubMed  Google Scholar 

  103. Kalra, H., Adda, C. G., Liem, M., Ang, C. S., Mechler, A., Simpson, R. J., et al. (2013). Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma. Proteomics, 13(22), 3354–3364. https://doi.org/10.1002/PMIC.201300282

    Article  CAS  PubMed  Google Scholar 

  104. Andaloussi, E. L., Lakhal, S., Mäger, S., Wood, I., Andaloussi, M. J. A. A., Lakhal, S. E. L., et al. (2013). Exosomes for targeted siRNA delivery across biological barriers. Advanced Drug Delivery Reviews, 65(3), 391–397. https://doi.org/10.1016/J.ADDR.2012.08.008

    Article  PubMed  Google Scholar 

  105. van der Meel, R., Fens, M. H. A. M., Vader, P., Van Solinge, W. W., Eniola-Adefeso, O., & Schiffelers, R. M. (2014). Extracellular vesicles as drug delivery systems: lessons from the liposome field. Journal of Controlled Release, 195, 72–85

    Article  PubMed  CAS  Google Scholar 

  106. Zhuang, X., Xiang, X., Grizzle, W., Sun, D., Zhang, S., Axtell, R. C., et al. (2011). Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Molecular Therapy, 19(10), 1769–1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Batrakova, E. V., & Kim, M. S. (2015). Using exosomes, naturally-equipped nanocarriers, for drug delivery. Journal of Controlled Release, 219, 396–405. https://doi.org/10.1016/j.jconrel.2015.07.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Xu, N., Wang, L., Guan, J., Tang, C., He, N., Zhang, W., & Fu, S. (2018). Wound healing effects of a Curcuma zedoaria polysaccharide with platelet-rich plasma exosomes assembled on chitosan/silk hydrogel sponge in a diabetic rat model. International Journal of Biological Macromolecules, 117, 102–107. https://doi.org/10.1016/j.ijbiomac.2018.05.066

    Article  CAS  PubMed  Google Scholar 

  109. Villata, S., Canta, M., & Cauda, V. (2020). EVs and bioengineering: from cellular products to engineered nanomachines. International Journal of Molecular Sciences, 21(17), 6048

    Article  CAS  PubMed Central  Google Scholar 

  110. Charoenviriyakul, C., Takahashi, Y., Morishita, M., Matsumoto, A., Nishikawa, M., & Takakura, Y. (2017). Cell type-specific and common characteristics of exosomes derived from mouse cell lines: Yield, physicochemical properties, and pharmacokinetics. European Journal of Pharmaceutical Sciences, 96, 316–322

    Article  CAS  PubMed  Google Scholar 

  111. Wiklander, O. P. B., Nordin, J. Z., O’Loughlin, A., Gustafsson, Y., Corso, G., Mäger, I., et al. (2015). Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. Journal of Extracellular Vesicles, 4(1), 26316

    Article  PubMed  Google Scholar 

  112. Mulcahy, L. A., Pink, R. C., & Carter, D. R. (2014). Routes and mechanisms of extracellular vesicle uptake. Journal of Extracellular Vesicles, 3. https://doi.org/10.3402/jev.v3.24641

  113. Yeo, R. W. Y., Lai, R. C., Zhang, B., Tan, S. S., Yin, Y., Teh, B. J., & Lim, S. K. (2013). Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Advanced Drug Delivery Reviews, 65(3), 336–341

    Article  CAS  PubMed  Google Scholar 

  114. Rani, S., & Ritter, T. (2016). The exosome - a naturally secreted nanoparticle and its application to wound healing. Advanced Materials, 28(27), 5542–5552

    Article  CAS  PubMed  Google Scholar 

  115. Zhang, B., Wang, M., Gong, A., Zhang, X., Wu, X., Zhu, Y., et al. (2015). HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing. Stem Cells, 33(7), 2158–2168. https://doi.org/10.1002/stem.1771

    Article  CAS  PubMed  Google Scholar 

  116. Antimisiaris, S. G., Mourtas, S., & Marazioti, A. (2018). Exosomes and exosome-inspired vesicles for targeted drug delivery. Pharmaceutics, 10(4), 218. https://doi.org/10.3390/pharmaceutics10040218

    Article  CAS  PubMed Central  Google Scholar 

  117. Golchin, A., Shams, F., & Karami, F. (2020). Advancing mesenchymal stem cell therapy with CRISPR/Cas9 for clinical trial studies, 1247. Advances in Experimental. Medicine and Biology, 89–100. Springer. https://doi.org/10.1007/5584_2019_459

  118. Zhang, Y., Bi, J., Huang, J., Tang, Y., Du, S., & Li, P. (2020). Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. International Journal of Nanomedicine, 15, 6917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Tian, T., Zhang, H. X., He, C. P., Fan, S., Zhu, Y. L., Qi, C., et al. (2018). Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials, 150, 137–149. https://doi.org/10.1016/j.biomaterials.2017.10.012

    Article  CAS  PubMed  Google Scholar 

  120. Man, K., Brunet, M. Y., Jones, M. C., & Cox, S. C. (2020). Engineered extracellular vesicles: tailored-made nanomaterials for medical applications. Nanomaterials, 10(9), https://doi.org/10.3390/nano10091838

  121. Warren, M. R., Zhang, C., Vedadghavami, A., Bokvist, K., Dhal, P. K., & Bajpayee, A. G. (2021). Milk exosomes with enhanced mucus penetrability for oral delivery of siRNA. Biomaterials Science, 9(12), 4260–4277. https://doi.org/10.1039/D0BM01497D

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Las Heras, K., Igartua, M., Santos-Vizcaino, E., & Hernandez, R. M. (2020). Chronic wounds: Current status, available strategies and emerging therapeutic solutions. Journal of Controlled Release, 328(September), 532–550. https://doi.org/10.1016/j.jconrel.2020.09.039

    Article  CAS  PubMed  Google Scholar 

  123. Khayambashi, P., Iyer, J., Pillai, S., Upadhyay, A., Zhang, Y., & Tran, S. D. (2021). Hydrogel encapsulation of mesenchymal stem cells and their derived exosomes for tissue engineering. International Journal of Molecular Sciences, 22(2), 1–15. https://doi.org/10.3390/ijms22020684

    Article  CAS  Google Scholar 

  124. Riha, S. M., Maarof, M., & Fauzi, M. B. (2021). Synergistic effect of biomaterial and stem cell for skin tissue engineering in cutaneous wound healing: a concise review. Polymers, 13(10), 1546. https://doi.org/10.3390/POLYM13101546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Mitrousis, N., Fokina, A., & Shoichet, M. S. (2018). Biomaterials for cell transplantation. Nature Reviews Materials, 3(11), 441–456. https://doi.org/10.1038/s41578-018-0057-0

    Article  CAS  Google Scholar 

  126. Zhao, S., Xu, Z., Wang, H., Reese, B. E., Gushchina, L. V., Jiang, M., et al. (2016). Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction. Nature Communications, 7, 1–12. https://doi.org/10.1038/ncomms13306

    Article  CAS  Google Scholar 

  127. Madl, C. M., Heilshorn, S. C., & Blau, H. M. (2018). Bioengineering strategies to accelerate stem cell therapeutics. Nature, 557, 335–342. https://doi.org/10.1038/s41586-018-0089-z

  128. Tao, S. C., Guo, S. C., Li, M., Ke, Q. F., Guo, Y. P., & Zhang, C. Q. (2017). Chitosan wound dressings incorporating exosomes derived from MicroRNA-126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model. Stem Cells Translational Medicine, 6(3), 736–747. https://doi.org/10.5966/SCTM.2016-0275

    Article  CAS  PubMed  Google Scholar 

  129. Qian, Z., Bai, Y., Zhou, J., Li, L., Na, J., Fan, Y., et al. (2020). A moisturizing chitosan-silk fibroin dressing with silver nanoparticles-adsorbed exosomes for repairing infected wounds. Journal of Materials Chemistry B, 8(32), 7197–7212. https://doi.org/10.1039/D0TB01100B

    Article  CAS  PubMed  Google Scholar 

  130. Shafei, S., Khanmohammadi, M., Heidari, R., Ghanbari, H., Taghdiri Nooshabadi, V., Farzamfar, S., et al. (2020). Exosome loaded alginate hydrogel promotes tissue regeneration in full-thickness skin wounds: An in vivo study. Journal of Biomedical Materials Research. Part A, 108(3), 545–556. https://doi.org/10.1002/JBM.A.36835

    Article  CAS  PubMed  Google Scholar 

  131. Wang, C., Liang, C., Wang, R., Yao, X., Guo, P., Yuan, W., et al. (2019). The fabrication of a highly efficient self-healing hydrogel from natural biopolymers loaded with exosomes for the synergistic promotion of severe wound healing. Biomaterials Science, 8(1), 313–324. https://doi.org/10.1039/C9BM01207A

    Article  PubMed  Google Scholar 

  132. Nooshabadi, V. T., Khanmohamadi, M., Valipour, E., Mahdipour, S., Salati, A., Malekshahi, Z. V., et al. (2020). Impact of exosome-loaded chitosan hydrogel in wound repair and layered dermal reconstitution in mice animal model. Journal of Biomedical Materials Research Part A, 108(11), 2138–2149. https://doi.org/10.1002/JBM.A.36959

    Article  CAS  PubMed  Google Scholar 

  133. Wang, C., Wang, M., Xu, T., Zhang, X., Lin, C., Gao, W., et al. (2019). Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics, 9(1), 65. https://doi.org/10.7150/THNO.29766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Shiekh, P. A., Singh, A., & Kumar, A. (2020). Exosome laden oxygen releasing antioxidant and antibacterial cryogel wound dressing OxOBand alleviate diabetic and infectious wound healing. Biomaterials, 249. https://doi.org/10.1016/J.BIOMATERIALS.2020.120020

  135. Zhao, D., Yu, Z., Li, Y., Wang, Y., Li, Q., & Han, D. (2020). GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration. Journal of Molecular Histology, 51(3), 251–263. https://doi.org/10.1007/S10735-020-09877-6

    Article  CAS  PubMed  Google Scholar 

  136. Willis, G. R., Kourembanas, S., & Mitsialis, S. A. (2017). Toward exosome-based therapeutics: isolation, heterogeneity, and fit-for-purpose potency. Frontiers in Cardiovascular Medicine, 4, 63

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Liu, B., Lee, B. W., Nakanishi, K., Villasante, A., Williamson, R., Metz, J., et al. (2018). Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells. Nature Biomedical Engineering, 2(5), 293–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Peppas, N. A., Hilt, J. Z., Khademhosseini, A., & Langer, R. (2006). Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Advanced Materials, 18(11), 1345–1360

    Article  CAS  Google Scholar 

  139. Mantha, S., Pillai, S., Khayambashi, P., Upadhyay, A., & Zhang, Y. (2019). Smart hydrogels in tissue engineering and regenerative medicine. Materials, 12(3323), 33

    Google Scholar 

  140. Wang, Y. (2018). Programmable hydrogels. Biomaterials, 178, 663–680. https://doi.org/10.1016/j.biomaterials.2018.03.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Riau, A. K., Ong, H. S., Yam, G. H. F., & Mehta, J. S. (2019). Sustained delivery system for stem cell-derived exosomes. Frontiers in Pharmacology, 10(November), 1–7. https://doi.org/10.3389/fphar.2019.01368

    Article  CAS  Google Scholar 

  142. Qin, Y., Wang, L., Gao, Z., Chen, G., & Zhang, C. (2016). Bone marrow stromal / stem cell- derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Nature Publishing Group, (February), 1–11. https://doi.org/10.1038/srep21961

  143. Islam, M. T., Rodríguez-Hornedo, N., Ciotti, S., & Ackermann, C. (2004). Rheological characterization of topical carbomer gels neutralized to different pH. Pharmaceutical Research, 21(7), 1192–1199. https://doi.org/10.1023/B:PHAM.0000033006.11619.07

    Article  CAS  PubMed  Google Scholar 

  144. Dai, T., Tanaka, M., Huang, Y. Y., & Hamblin, M. R. (2011). Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects. Expert Review of Anti-infective Therapy, 9(7), 857–879. https://doi.org/10.1586/ERI.11.59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Kapoor, S., & Kundu, S. C. (2016). Silk protein-based hydrogels: Promising advanced materials for biomedical applications. Acta Biomaterialia, 31, 17–32. https://doi.org/10.1016/J.ACTBIO.2015.11.034

    Article  CAS  PubMed  Google Scholar 

  146. Khanmohammadi, M., Nemati, S., Ai, J., & Khademi, F. (2019). Multipotency expression of human adipose stem cells in filament-like alginate and gelatin derivative hydrogel fabricated through visible light-initiated crosslinking. Materials Science & Engineering. C, Materials for Biological Applications, 103. https://doi.org/10.1016/J.MSEC.2019.109808

  147. Shafei, S., Khanmohammadi, M., Heidari, R., Ghanbari, H., Nooshabadi, V. T., Farzamfar, S., et al. (2020). Exosome loaded alginate hydrogel promotes tissue regeneration in full-thickness skin wounds: An in vivo study. Journal of biomedical materials research. Part A 108(3),545–556. https://doi.org/10.1002/JBM.A.36835

  148. Zhao, D., Yu, Z., Li, Y., Wang, Y., Li, Q., & Han, D. (2020). GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration. Journal of Molecular Histology, 51(3),251–263. https://doi.org/10.1007/S10735-020-09877-6

  149. Shiekh, P. A., Singh, A., & Kumar, A. (2020). Exosome laden oxygen releasing antioxidant and antibacterial cryogel wound dressing OxOBand alleviate diabetic and infectious wound healing. Biomaterials, 249, 120020. https://doi.org/10.1016/J.BIOMATERIALS.2020.120020

    Article  CAS  PubMed  Google Scholar 

  150. Chen, W. J., Huang, J. W., Niu, C. C., Chen, L. H., Yuan, L. J., Lai, P. L., et al. (2009). Use of fluorescence labeled mesenchymal stem cells in pluronic F127 and porous hydroxyapatite as a bone substitute for posterolateral spinal fusion. Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society, 27(12), 1631–1636. https://doi.org/10.1002/JOR.20925

    Article  Google Scholar 

  151. Lou, P., Liu, S., Xu, X., Pan, C., Lu, Y., & Liu, J. (2021). Extracellular vesicle-based therapeutics for the regeneration of chronic wounds: current knowledge and future perspectives. Acta Biomaterialia, 119, 42–56. https://doi.org/10.1016/J.ACTBIO.2020.11.001

    Article  CAS  PubMed  Google Scholar 

  152. Jing, H., He, X., & Zheng, J. (2018). Exosomes and regenerative medicine: state of the art and perspectives. Translational Research: the Journal of Laboratory and Clinical Medicine, 196, 1–16. https://doi.org/10.1016/J.TRSL.2018.01.005

    Article  CAS  Google Scholar 

  153. Zhou, Y., Kosaka, N., Xiao, Z., & Ochiya, T. (2020). MSC-exosomes in regenerative medicine. Exosomes, 433–465. https://doi.org/10.1016/B978-0-12-816053-4.00019-5

  154. Aramwit, P. (2016). Introduction to biomaterials for wound healing. Wound Healing Biomaterials, 2, 3–38. https://doi.org/10.1016/B978-1-78242-456-7.00001-5

    Article  CAS  Google Scholar 

  155. Ige, O. O., Umoru, L. E., & Aribo, S. (2012). Natural products: a minefield of biomaterials. ISRN Materials Science, 2012, 1–20. https://doi.org/10.5402/2012/983062

    Article  CAS  Google Scholar 

  156. Chen, P., Zheng, L., Wang, Y., Tao,., Xie, Z., Xia, C., et al. (2019). Desktop stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration. Theranostics, 9(9), 2439–2459. https://doi.org/10.7150/THNO.31017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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The schematic representations were created by Biorender (©BioRender - biorender.com) and with an approved license. Additionally, the graphical abstract was designed by Inkscape 1.1.

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Authors and Affiliations

  1. Department of Clinical Biochemistry and Applied Cell Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

    Ali Golchin, Parviz Ranjbarvan, Shiva Gholizadeh-Ghaleh Aziz, Sanaz Sadigh & Yousef Rasmi

  2. Department of Medical Biotechnology, School of Advanced Technologies in MedicineShahid, Beheshti University of Medical Sciences, Tehran, Iran

    Forough Shams

  3. Department of Biomaterials and Tissue Engineering, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Arefeh Basiri

  4. Department of Tissue Engineering & Regenerative Medicine, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Mazandaran, Iran

    Samaneh Kiani

  5. Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Roya Sarkhosh-Inanlou & Yousef Rasmi

  6. Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Abdolreza Ardeshirylajimi

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A.G. conceptualized the study; all authors cooperated in the drafting and writing the manuscript and approving it for submission.

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This article belongs to the Topical Collection: Special Issue on Stem Cell Technology and Skin Disorders (Dermatology): from Stem Cell Biology to Clinical Application.

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Golchin, A., Shams, F., Basiri, A. et al. Combination Therapy of Stem Cell-derived Exosomes and Biomaterials in the Wound Healing. Stem Cell Rev and Rep 18, 1892–1911 (2022). https://doi.org/10.1007/s12015-021-10309-5

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