CURRENT ASPECTS OF REPARATIVE REGENERATION OF SKIN: A MODERN VIEW ON THE PROBLEM
DOI:
https://doi.org/10.11603/1811-2471.2024.v.i4.15020Keywords:
skin, reparative regeneration, stem cells, exosomes, wound healing, bioengineered skin substituteAbstract
SUMMARY. During ontogenesis, the epidermis is constantly affected by a wide range of environmental factors that can potentially cause negative consequences of various nature: changes of skin homeostasis, dystrophic, destructive, atrophic changes, premature aging, wound formation, etc. Such environmental factors are traumatic injuries, solar radiation, pathogens of infectious diseases, exposure to high and low environmental temperatures, aggressive chemicals, and others. The high frequency of skin trauma stimulates research into the peculiarities of the structural and functional organization of damaged skin and the development of methods for optimizing the reparative regeneration of the skin with the use of modern technologies.
The aim – to analyze modern literature data on the structural and physiological aspects of skin regeneration and the possibilities of their stimulation.
Material and Methods. The method of system analysis and the analytical method of searching and researching information acquired from scientometric databases and search systems of scientific information are used.
Results. The main directions of theoretical and experimental research of the modern biology and medicine, dedicated to reparative regeneration of skin, are the following: the use of stem cells and their derivatives – exosomes, the development of nanotechnology, in particular, the use of silica nanoparticles, the design of skin substitutes. It has also been proven that selenium and copper compounds have a positive effect for increasing the overall resistance of the skin. The use of mesenchymal stem cells and stem cells of adipose origin contribute to angiogenesis, the adequate course of inflammation and immune response, stimulate cell proliferation and re-epithelialization. A promising direction is work on the creation of bioengineered skin substitutes with adequate morpho-physiological characteristics.
Conclusions. The study of structural and physiological aspects of reparative skin regeneration is relevant, given the high percentage of skin injuries and the imperfection of existing methods of promoting the healing of significant skin defects. Prospective directions for solving this problem are the search for sources of undifferentiated cells, the development of effective methods of their proliferation and differentiation, the creation of skin substitutes, the improvement of methods of treating skin wounds, and the prevention of the development of fibrous scars.
References
Jobeili, L., Rousselle, P., Béal, D., Blouin, E., Roussel, A.M., Damour, O., & Rachidi, W. (2017). Selenium preserves keratinocyte stemness and delays senescence by maintaining epidermal adhesion. Aging (Albany NY), 25;9(11), 2302-2315. DOI: 10.18632/aging.101322. PMID: 29176034; PMCID: PMC5723688. DOI: https://doi.org/10.18632/aging.101322
Guillamat-Prats, R. (2021). The Role of MSC in Wound Healing, Scarring and Regeneration. Cells, 8;10(7), 1729. DOI: 10.3390/cells10071729. PMID: 34359898; PMCID: PMC8305394. DOI: https://doi.org/10.3390/cells10071729
Arriagada, F., Nonell, S., & Morales, J. (2019). Silica-based nanosystems for therapeutic applications in the skin. Nanomedicine (Lond), 14(16), 2243-2267. DOI: 10.2217/nnm-2019-0052. Epub 2019 Aug 14. PMID: 31411537. DOI: https://doi.org/10.2217/nnm-2019-0052
Rousselle, P., Laigle, C., & Rousselet, G. (2022). The basement membrane in epidermal polarity, stemness, and regeneration. Am J Physiol Cell Physiol, 1;323(6), C1807-C1822. DOI: 10.1152/ajpcell.00069.2022. Epub 2022 Nov 14. PMID: 36374168. DOI: https://doi.org/10.1152/ajpcell.00069.2022
Arriagada, F., & Morales, J. (2019). Limitations and Opportunities in Topical Drug Delivery: Interaction Between Silica Nanoparticles and Skin Barrier. Curr Pharm Des, 25(4), 455-466. DOI: 10.2174/1381612825666190404121507. PMID: 30947656. DOI: https://doi.org/10.2174/1381612825666190404121507
Hooshmand, S., Mollazadeh, S., Akrami, N., Ghanad, M., El-Fiqi, A., Baino, …& Kargozar, S. (2021). Mesoporous Silica Nanoparticles and Mesoporous Bioactive Glasses for Wound Management: From Skin Regeneration to Cancer Therapy. Materials (Basel), 17, 14(12), 3337. DOI: 10.3390/ ma14123337. PMID: 34204198; PMCID: PMC8235211. DOI: https://doi.org/10.3390/ma14123337
Altobelli, G.G., Van Noorden, S., Balato, A., & Cimini, V. (2020). Copper/Zinc Superoxide Dismutase in Human Skin: Current Knowledge. Front Med (Lausanne), 12(7), 183. DOI: 10.3389/fmed.2020.00183. PMID: 32478084; PMCID: PMC7235401. DOI: https://doi.org/10.3389/fmed.2020.00183
Ogen-Shtern, N., Chumin, K., Silberstein, E., & Borkow, G. (2021). Copper Ions Ameliorated Thermal Burn-Induced Damage in ex vivo Human Skin Organ Culture. Skin Pharmacol Physiol, 34(6), 317-327. DOI: 10.1159/ 000517194. Epub 2021 Jul 8. PMID: 34237749. DOI: https://doi.org/10.1159/000517194
Wang, T.L., Zhou, Z.F., Liu, J.F., Hou, X.D., Zhou, Z., Dai, Y.L., … & Zheng, L.P. (2021). Donut-like MOFs of copper/nicotinic acid and composite hydrogels with superior bioactivity for rh-bFGF delivering and skin wound healing. J Nanobiotechnology, 9;19(1), 275. DOI: 10.1186/s12951-021-01014-z. PMID: 34503490; PMCID: PMC8427876. DOI: https://doi.org/10.1186/s12951-021-01014-z
Ogen-Shtern, N., Chumin, K., Cohen, G., & Borkow, G. (2020). Increased pro-collagen 1, elastin, and TGF-β1 expression by copper ions in an ex-vivo human skin model. J Cosmet Dermatol, 19(6), 1522-1527. DOI: 10.1111/ jocd.13186. Epub 2019 Oct 11. PMID: 31603269. DOI: https://doi.org/10.1111/jocd.13186
An, Y., Lin, S., Tan, X., Zhu, S., Nie, F., Zhen, Y., ... & Wu, J. (2021). Exosomes from adipose-derived stem cells and application to skin wound healing. Cell Prolif, 54(3), e12993. DOI: 10.1111/cpr.12993. Epub 2021 Jan 17. PMID: 33458899; PMCID: PMC7941238. DOI: https://doi.org/10.1111/cpr.12993
Alapure, B.V., Lu, Y., He, M., Chu, C.C., Peng, H., Muhale, F., ... & Hong, S. (2018). Accelerate Healing of Severe Burn Wounds by Mouse Bone Marrow Mesenchymal Stem Cell-Seeded Biodegradable Hydrogel Scaffold Synthesized from Arginine-Based Polyester amide and Chitosan. Stem Cells Dev, 1;27(23), 1605-1620. DOI: 10.1089/scd.2018.0106. Epub 2018 Oct 23. PMID: 30215325; PMCID: PMC6276600. DOI: https://doi.org/10.1089/scd.2018.0106
Zhang, J., Guan, J., Niu, X., Hu, G., Guo, S., Li, Q., ... & Wang, Y. (2015). Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med, 1(13), 49. DOI: 10.1186/s12967-015-0417-0. PMID: 25638205; PMCID: PMC4371881. DOI: https://doi.org/10.1186/s12967-015-0417-0
Millán-Rivero, J.E., Martínez, C.M., Romecín, P.A., Aznar-Cervantes, S.D., Carpes-Ruiz, M., Cenis, J.L., ... & García-Bernal, D. (2019). Silk fibroin scaffolds seeded with Wharton's jelly mesenchymal stem cells enhance re-epithelialization and reduce formation of scar tissue after cutaneous wound healing. Stem Cell Res Ther, 27;10(1), 126. DOI: 10.1186/s13287-019-1229-6. PMID: 31029166; PMCID: PMC6487033 DOI: https://doi.org/10.1186/s13287-019-1229-6
Lasocka, I., Jastrzębska, E., Szulc-Dąbrowska, L., Skibniewski, M., Pasternak, I., Kalbacova, M.H., & Skibniewska, E.M. (2019). The effects of graphene and mesenchymal stem cells in cutaneous wound healing and their putative action mechanism. Int J Nanomedicine, 1(14), 2281-2299. DOI: 10.2147/IJN.S190928. PMID: 31015759; PMCID: PMC6448540 DOI: https://doi.org/10.2147/IJN.S190928
Li, Z., Wang, H., Yang, B., Sun, Y., & Huo, R. (2015). Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring. Mater Sci Eng C Mater Biol Appl, 1(57), 181-8. DOI: 10.1016/j.msec.2015.07.062. Epub 2015 Jul 30. PMID: 26354253 DOI: https://doi.org/10.1016/j.msec.2015.07.062
Laverdet, B., Micallef, L., Lebreton, C., Mollard, J., Lataillade, J.J., Coulomb, B., & Desmoulière, A. (2014). Use of mesenchymal stem cells for cutaneous repair and skin substitute elaboration. Pathol Biol (Paris), 62(2), 108-17. DOI: 10.1016/j.patbio.2014.01.002. Epub 2014 Mar 21. PMID: 24661975. DOI: https://doi.org/10.1016/j.patbio.2014.01.002
Ju, Y., Hu, Y., Yang, P., Xie, X., & Fang, B. (2022). Extracellular vesicle-loaded hydrogels for tissue repair and regeneration. Mater Today Bio, 21(18), 100522. DOI: 10.1016/j.mtbio.2022.100522. PMID: 36593913; PMCID: PMC9803958. DOI: https://doi.org/10.1016/j.mtbio.2022.100522
Ojeh, N.O., & Navsaria, H.A. (2014). An in vitro skin model to study the effect of mesenchymal stem cells in wound healing and epidermal regeneration. J Biomed Mater Res A, 102(8), 2785-92. DOI: 10.1002/jbm.a.34950. Epub 2013 Sep 30. PMID: 24115470. DOI: https://doi.org/10.1002/jbm.a.34950
Farhadihosseinabadi, B., Farahani, M., Tayebi, T., Jafari, A., Biniazan, F., Modaresifar, K., ... & Niknejad, H. (2018). Amniotic membrane and its epithelial and mesenchymal stem cells as an appropriate source for skin tissue engineering and regenerative medicine. Artif Cells Nanomed Biotechnol, 46(sup2), 431-440. DOI: 10.1080/21691401.2018. 1458730. Epub 2018 Apr 24. PMID: 29687742. DOI: https://doi.org/10.1080/21691401.2018.1458730
Yu, S.C., Xu, Y.Y., Li, Y., Xu, B., Sun,. Q, Li, F., & Zhang, X.G. (2015). Construction of tissue engineered skin with human amniotic mesenchymal stem cells and human amniotic epithelial cells. Eur Rev Med Pharmacol Sci, 19(23), 4627-35. PMID: 26698261.
El Sadik, A.O., El Ghamrawy, T.A., & Abd El-Galil, T.I. (2015). The Effect of Mesenchymal Stem Cells and Chitosan Gel on Full Thickness Skin Wound Healing in Albino Rats: Histological, Immunohistochemical and Fluorescent Study. PLoS One, 24;10(9), e0137544. DOI: 10.1371/journal.pone.0137544. PMID: 26402454; PMCID: PMC4581728. DOI: https://doi.org/10.1371/journal.pone.0137544
Mazini, L., Rochette, L., Admou, B., Amal, S., & Malka, G. (2020). Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing. Int J Mol Sci, 14;21(4), 1306. DOI: 10.3390/ijms21041306. PMID: 32075181; PMCID: PMC7072889. DOI: https://doi.org/10.3390/ijms21041306
Xiao, Y., Peng, J., Liu, Q., Chen, L., Shi, K., Han, R., ... & Qian, Z. (2020). Ultrasmall CuS@BSA nanoparticles with mild photothermal conversion synergistically induce MSCs-differentiated fibroblast and improve skin regeneration. Theranostics, 1;10(4), 1500-1513. DOI: 10.7150/thno.39471. PMID: 32042318; PMCID: PMC6993219. DOI: https://doi.org/10.7150/thno.39471
Kim, W.S., Park, B.S., & Sung, J.H. (2009). The wound-healing and antioxidant effects of adipose-derived stem cells. Expert Opin Biol Ther, 9(7), 879-87. DOI: 10.1517/14712590903039684. PMID: 19522555. DOI: https://doi.org/10.1517/14712590903039684
Kim, W.S., Park, B.S., Kim, H.K., Park, J.S., Kim, K.J., Choi, J.S., ... & Sung, J.H. (2008). Evidence supporting antioxidant action of adipose-derived stem cells: protection of human dermal fibroblasts from oxidative stress. J Dermatol Sci, 49(2), 133-42. DOI: 10.1016/j.jdermsci.2007.08.004. Epub 2007 Sep 17. PMID: 17870415. DOI: https://doi.org/10.1016/j.jdermsci.2007.08.004
Jiang, L.W., Chen, H., & Lu, H. (2016). Using human epithelial amnion cells in human de-epidermized dermis for skin regeneration. J Dermatol Sci, 81(1), 26-34. DOI: 10.1016/j.jdermsci.2015.10.018. Epub 2015 Oct 31. PMID: 26596214. DOI: https://doi.org/10.1016/j.jdermsci.2015.10.018
Mashinchian, O., Bonakdar, S., Taghinejad, H., Satarifard, V., Heidari, M., Majidi, M., ... & Mahmoudi, M. (2014). Cell-imprinted substrates act as an artificial niche for skin regeneration. ACS Appl Mater Interfaces, 13;6(15), 13280-92. DOI: 10.1021/am503045b. Epub 2014 Jul 10. PMID: 24967724. DOI: https://doi.org/10.1021/am503045b
Chavez-Munoz, C., Nguyen, K.T., Xu, W., Hong, S.J., Mustoe, T.A., & Galiano, R.D. (2013). Transdifferentiation of adipose-derived stem cells into keratinocyte-like cells: engineering a stratified epidermis. PLoS One, 2; 8(12), e80587. DOI: 10.1371/journal.pone.0080587. PMID: 24312483; PMCID: PMC3846628. DOI: https://doi.org/10.1371/journal.pone.0080587
Karppinen, S.M., Heljasvaara, R., Gullberg, D., Tasanen, K., & Pihlajaniemi, T. (2019). Toward understanding scarless skin wound healing and pathological scarring. F1000Res, 5(8), F1000 Faculty Rev-787. DOI: 10.12688/f1000research.18293.1. PMID: 31231509; PMCID: PMC6556993. DOI: https://doi.org/10.12688/f1000research.18293.1
Frech, S., Forsthuber, A., Korosec, A., Lipp, K., Kozumov, V., & Lichtenberger, B.M. (2022). Hedgehog Signaling in Papillary Fibroblasts Is Essential for Hair Follicle Regeneration during Wound Healing. J Invest Dermatol, 142(6), 1737-1748.e5. DOI: 10.1016/j.jid.2021.11.026. Epub 2021 Dec 16. PMID: 34922948. DOI: https://doi.org/10.1016/j.jid.2021.11.026
Lingzhi, Z., Meirong, L., & Xiaobing, F. (2020). Biological approaches for hypertrophic scars. Int Wound J, 17(2), 405-418. DOI: 10.1111/iwj.13286. Epub 2019 Dec 20. PMID: 31860941; PMCID: PMC7948781. DOI: https://doi.org/10.1111/iwj.13286
Xue, M., Zhao, R., March, L., & Jackson, C. (2022). Dermal Fibroblast Heterogeneity and Its Contribution to the Skin Repair and Regeneration. Adv Wound Care (New Rochelle), 11(2), 87-107. DOI: 10.1089/wound.2020.1287. Epub 2021 Mar 23. PMID: 33607934 DOI: https://doi.org/10.1089/wound.2020.1287
Woodley, D.T. (2017). Distinct Fibroblasts in the Papillary and Reticular Dermis: Implications for Wound Healing. Dermatol Clin, 35(1), 95-100. DOI: 10.1016/j.det.2016.07.004. PMID: 27890241. DOI: https://doi.org/10.1016/j.det.2016.07.004
Abbasi, S., Sinha, S., Labit, E., Rosin, N.L., Yoon, G., Rahmani, W., ... & Biernaskie, J. (2020). Distinct Regulatory Programs Control the Latent Regenerative Potential of Dermal Fibroblasts during Wound Healing. Cell Stem Cell, 3;27(3), 396-412.e6. DOI: 10.1016/j.stem.2020.07.008. Epub 2020 Aug 4. Erratum in: Cell Stem Cell, 2021 Mar 4;28(3):581-583. PMID: 32755548. DOI: https://doi.org/10.1016/j.stem.2020.07.008
Hesketh, M., Sahin, K.B., West, Z.E., & Murray, R.Z. (2017). Macrophage Phenotypes Regulate Scar Formation and Chronic Wound Healing. Int J Mol Sci, 17;18(7), 1545. DOI: 10.3390/ijms18071545. PMID: 28714933; PMCID: PMC5536033. DOI: https://doi.org/10.3390/ijms18071545
Al Sadoun, H. (2022). Macrophage Phenotypes in Normal and Diabetic Wound Healing and Therapeutic Interventions. Cells, 5;11(15), 2430. DOI: 10.3390/cells11152430. PMID: 35954275; PMCID: PMC9367932. DOI: https://doi.org/10.3390/cells11152430
Duscher, D., Maan, Z.N., Wong, V.W., Rennert, R.C., Januszyk, M., Rodrigues, M., ... & Gurtner, G.C. (2014). Mechanotransduction and fibrosis. J Biomech, 27;47(9), 1997-2005. DOI: 10.1016/j.jbiomech.2014.03.031. Epub 2014 Mar 26. PMID: 24709567; PMCID: PMC4425300. DOI: https://doi.org/10.1016/j.jbiomech.2014.03.031
Ogawa, R., & Akaishi, S. (2016). Endothelial dysfunction may play a key role in keloid and hypertrophic scar pathogenesis - Keloids and hypertrophic scars may be vascular disorders. Med Hypotheses, 96, 51-60. DOI: 10.1016/j.mehy.2016.09.024. Epub 2016 Sep 28. PMID: 27959277. DOI: https://doi.org/10.1016/j.mehy.2016.09.024
Chiang, R.S., Borovikova, A.A., King, K., Banyard, D.A., Lalezari, S., Toranto, J.D., ... & Widgerow, A.D. (2016). Current concepts related to hypertrophic scarring in burn injuries. Wound Repair Regen, 24(3), 466-77. DOI: 10.1111/wrr.12432. Epub 2016 May 6. PMID: 27027596; PMCID: PMC5802966 DOI: https://doi.org/10.1111/wrr.12432
Amadeu, T., Braune, A., Mandarim-de-Lacerda, C., Porto, L.C., Desmoulière, A., & Costa, A. (2003). Vascularization pattern in hypertrophic scars and keloids: a stereological analysis. Pathol Res Pract, 199(7), 469-73. DOI: 10.1078/0344-0338-00447. PMID: 14521263. DOI: https://doi.org/10.1078/0344-0338-00447
Yang, S.W., Geng, Z.J., Ma, K., Sun, X.Y., & Fu, X.B. (2016). Comparison of the histological morphology between normal skin and scar tissue. J Huazhong Univ Sci Technolog Med Sci, 36(2), 265-269. DOI: 10.1007/s11596-016-1578-7. Epub 2016 Apr 13. PMID: 27072974. DOI: https://doi.org/10.1007/s11596-016-1578-7
Jackson, W.M., Nesti, L.J., & Tuan, R.S. (2012). Mesenchymal stem cell therapy for attenuation of scar formation during wound healing. Stem Cell Res Ther, 31;3(3), 20. DOI: 10.1186/scrt111. PMID: 22668751; PMCID: PMC3392767. DOI: https://doi.org/10.1186/scrt111
