Intrinsic and extrinsic aspects of the abnormal tissue healing process
DOI:
https://doi.org/10.20883/Keywords:
plastic surgery, hypertrophic scar, healingAbstract
Introduction. Hypertrophic scars and keloids are consequences of abnormalities in the healing process and tissue repair, characterized by excessive fibrosis present throughout the wound distribution. In this sense, there are several extrinsic and intrinsic factors that corroborate the hypertrophic healing process.
Aim. To analyze which morphological and metabolic factors accentuate the incidence of hypertrophic scars and keloids in healing processes in the last five years.
Material and methods. Systematic review study without meta-analysis outlined by the PRISMA protocol and registered in PROSPERO from the literature bases in the broad area of knowledge of Health Science: PubMed, Virtual Health Library (BVS), Periódico Capes and LILACS. The research was carried out by crossing the following descriptors: “plastic surgery”, “hypertrophic scar” and “healing”, in which articles written and published from 2020 to 2023 were used.
Results. Molecular aspects of tissue modulation, hypertension, genetic factors of single nucleotide polymorphisms and factors related to lifestyle can influence the occurrence of abnormal scars.
Conclusions. Hypertrophic scars and keloids are related to extrinsic and intrinsic factors, such as metabolic causes and the patient's postoperative course.
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Ghazawi, F. M., Zargham, R., Gilardino, M. S., Sasseville, D., & Jafarian, F. (2018). Insights into the pathophysiology of hypertrophic scars and keloids: how do they differ?. Advances in skin & wound care, 31(1), 582-595. https://doi.org/10.1097/01.asw.0000527576.27489.0f
Ibrahim, N. E., Shaharan, S., & Dheansa, B. (2020). Adverse effects of pregnancy on keloids and hypertrophic scars. Cureus, 12(12). https://doi.org/10.7759/cureus.12154
Koppenol, D. C., Vermolen, F. J., Niessen, F. B., van Zuijlen, P. P., & Vuik, K. (2017). A mathematical model for the simulation of the formation and the subsequent regression of hypertrophic scar tissue after dermal wounding. Biomechanics and modeling in mechanobiology, 16, 15-32. https://doi.org/10.1007/s10237-016-0799-9
Macarak, E. J., Wermuth, P. J., Rosenbloom, J., & Uitto, J. (2021). Keloid disorder: fibroblast differentiation and gene expression profile in fibrotic skin diseases. Experimental Dermatology, 30(1), 132-145. https://doi.org/10.1111/exd.14243
Chen, Q., Zhao, T., Xie, X., Yu, D., Wu, L., Yu, W., & Sun, W. (2018). MicroRNA 663 regulates the proliferation of fibroblasts in hypertrophic scars via transforming growth factor β1. Experimental and Therapeutic Medicine, 16(2), 1311-1317. https://doi.org/10.3892/etm.2018.6350
Li, X. P., Liu, P., Li, Y. F., Zhang, G. L., Zeng, D. S., & Liu, D. L. (2019). LPS induces activation of the TLR4 pathway in fibroblasts and promotes skin scar formation through collagen I and TGF-β in skin lesions. International Journal of Clinical and Experimental Pathology, 12(6), 2121.
Nabai, L., Pourghadiri, A., & Ghahary, A. (2020). Hypertrophic scarring: current knowledge of predisposing factors, cellular and molecular mechanisms. Journal of Burn Care & Research, 41(1), 48-56. https://doi.org/10.1093/jbcr/irz158
Wang, Z. C., Zhao, W. Y., Cao, Y., Liu, Y. Q., Sun, Q., Shi, P., ... & Tan, W. Q. (2020). The roles of inflammation in keloid and hypertrophic scars. Frontiers in Immunology, 11, 603187. https://doi.org/10.3389/fimmu.2020.603187
Limandjaja, G. C., Niessen, F. B., Scheper, R. J., & Gibbs, S. (2021). Hypertrophic scars and keloids: Overview of the evidence and practical guide for differentiating between these abnormal scars. Experimental Dermatology, 30(1), 146-161. https://doi.org/10.1111/exd.14121
Yuan, R., Dai, X., Li, Y., Li, C., & Liu, L. (2021). Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-β2/Smad3 signaling. Molecular Medicine Reports, 24(5), 1-12. https://doi.org/10.3892/mmr.2021.12398
Ogawa, R. (2022). The most current algorithms for the treatment and prevention of hypertrophic scars and keloids: a 2020 update of the algorithms published 10 years ago. Plastic and reconstructive surgery, 149(1), 79. https://doi.org/10.1097%2FPRS.0000000000008667
Xie, F., Teng, L., Lu, J., Xu, J., Zhang, C., Yang, L., ... & Zhao, M. (2022). Interleukin-10-Modified Adipose-Derived Mesenchymal Stem Cells Prevent Hypertrophic Scar Formation via Regulating the Biological Characteristics of Fibroblasts and Inflammation. Mediators of Inflammation, 2022. https://doi.org/10.1155/2022/6368311
Zhou, Y., Zhao, Y., Du, H., Suo, Y., Chen, H., Li, H., ... & Huang, X. (2020). Downregulation of CFTR is involved in the formation of hypertrophic scars. BioMed Research International, 2020. https://doi.org/10.1155/2020/9526289
Raktoe, R. S., Rietveld, M. H., Out-Luiting, J. J., Kruithof-de Julio, M., van Zuijlen, P. P., van Doorn, R., & El Ghalbzouri, A. (2021). The effect of TGFβRI inhibition on fibroblast heterogeneity in hypertrophic scar 2D in vitro models. Burns, 47(7), 1563-1575. https://doi.org/10.1016/j.burns.2021.01.004
Mouawad, J. E., Heywood, J., Armstrong, M. B., Ogunleye, A., & Feghali-Bostwick, C. (2022). Low Baseline Expression of Fibrotic Genes in an Ex Vivo Human Skin Model is a Potential Indicator of Excessive Skin Scarring. Plastic and Reconstructive Surgery–Global Open, 10(11), e4626. https://doi.org/10.1097/GOX.0000000000004626
Jiang, D., Guo, B., Lin, F., Hui, Q., & Tao, K. (2020). Effect of THBS1 on the biological function of hypertrophic scar fibroblasts. BioMed Research International, 2020. https://doi.org/10.1155/2020/8605407
Rössler, S., Nischwitz, S. P., Luze, H., Holzer-Geissler, J. C., Zrim, R., & Kamolz, L. P. (2022). In Vivo Models for Hypertrophic Scars—A Systematic Review. Medicina, 58(6), 736. https://doi.org/10.3390/medicina58060736
Direder, M., Weiss, T., Copic, D., Vorstandlechner, V., Laggner, M., Pfisterer, K., ... & Mildner, M. (2022). Schwann cells contribute to keloid formation. Matrix Biology, 108, 55-76. https://doi.org/10.1016/j.matbio.2022.03.001
Wang, Q., Miao, M., Qin, Z., Li, B., & Niu, X. (2020). Lower Metal Element Levels in Hypertrophic Scars: A Potential Mechanism of Aberrant Cicatrix Hyperplasia. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 26, e925202-1. https://doi.org/10.12659%2FMSM.925202
Guerrero Serrano, L. (2020). Cicatriz hipertrófica y queloide: rompiendo paradigmas con el uso de Z-plastias. Cirugía Plástica Ibero-Latinoamericana, 46(2), 177-186. https://dx.doi.org/10.4321/s0376-78922020000300007
Caicedo Escudero, D. M., Rengel Maldonado, J. F., & Torres Toala, F. G. (2020). Keloid scar recurrence in patients treated with surgical resection plus radiotherapy (in Spanish).
Vorstandlechner, V., Laggner, M., Copic, D., Klas, K., Direder, M., Chen, Y., ... & Mildner, M. (2021). The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation. Nature Communications, 12(1), 6242. https://doi.org/10.1038/s41467-021-26495-2
Chen, B., Li, H., & Xia, W. (2020). The role of Th1/Th2 cell chemokine expression in hypertrophic scar. International Wound Journal, 17(1), 197-205. https://doi.org/10.1111/iwj.13257
Zhu, D. Z., Yao, B., Cui, X. L., Huang, S., & Fu, X. (2021). Effects and mechanism of age on the stiffness and the fibrotic phenotype of fibroblasts of human hypertrophic scar. Zhonghua Shao Shang za zhi= Zhonghua Shaoshang Zazhi= Chinese Journal of Burns, 37(10), 937-945. https://doi.org/10.3760/cma.j.cn501120-20200810-00374
Pangkanon, W., Yenbutra, P., Kamanamool, N., Tannirandorn, A., & Udompataikul, M. (2021). A comparison of the efficacy of silicone gel containing onion extract and aloe vera to silicone gel sheets to prevent postoperative hypertrophic scars and keloids. Journal of Cosmetic Dermatology, 20(4), 1146-1153. https://doi.org/10.1111/jocd.13933
Zhang, J., Zhou, S., Xia, Z., Peng, Z., Cheng, X., Yang, X., ... & Yang, R. (2021). 595-nm pulsed dye laser combined with fractional CO 2 laser reduces hypertrophic scar through down-regulating TGFβ1 and PCNA. Lasers in Medical Science, 36, 1625-1632. https://doi.org/10.1007/s10103-020-03240-7
Li, L., Yuan, C., Zhang, X., Wang, B., & Yan, Y. (2021). Superficial X‐ray‐induced hyperpigmentation in postoperative keloid radiotherapy: A study of 70 keloids to identify clinical features and risk factors. Journal of Cosmetic Dermatology, 20(9), 2880-2886. https://doi.org/10.1111/jocd.14308
Dai, X., & Lei, T. C. (2021). Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells. Basic & Clinical Pharmacology & Toxicology, 129(6), 462-469. https://doi.org/10.1111/bcpt.13661
Tan, A., Luna, O. M., & Glass, D. A. (2020). Pentoxifylline for the prevention of postsurgical keloid recurrence. Dermatologic surgery: official publication for American Society for Dermatologic Surgery [et al.], 46(10), 1353. https://doi.org/10.1097%2FDSS.0000000000002090
EA, E. H. E. A., FM, A. A. S., El-Hafiz, H. S. A., & Maghraby, H. M. (2022). Fractional Carbon Dioxide (CO 2) Laser Alone Versus Fractional CO 2 Laser Combined With Triamcinolone Acetonide or Trichloroacetic Acid in Keloid Treatment: A Comparative Clinical and Radiological Study. Dermatology Practical & Conceptual, 12(2), e2022072-e2022072. https://doi.org/10.5826/dpc.1202a72
Seago, M., Shumaker, P. R., Spring, L. K., Alam, M., Al‐Niaimi, F., Rox Anderson, R., ... & Waibel, J. (2020). Laser treatment of traumatic scars and contractures: 2020 international consensus recommendations. Lasers in surgery and medicine, 52(2), 96-116. https://doi.org/10.1002/lsm.23201
Ud-Din, S., Wilgus, T. A., McGeorge, D. D., & Bayat, A. (2021). Pre-emptive priming of human skin improves cutaneous scarring and is superior to immediate and delayed topical anti-scarring treatment post-wounding: a double-blind randomised placebo-controlled clinical trial. Pharmaceutics, 13(4), 510. https://doi.org/10.3390/pharmaceutics13040510
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. PMID: 33782057; PMCID: PMC8005924. https://doi.org/10.1136/bmj.n71
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