REFERENCES
4. Willenborg S, Injarabian L, Eming SA. Role of macrophages in wound healing. Cold Spring Harb Perspect Biol. 2022;14:a041216.
6. Trace AP, Enos CW, Mantel A, Harvey VM. Keloids and hypertrophic scars: a spectrum of clinical challenges. Am J Clin Dermatol. 2016;17:201-23.
7. Fang X, Wang Y, Chen H, et al. Hypertrophic scarring and keloids: epidemiology, molecular pathogenesis, and therapeutic interventions. MedComm. 2025;6:e70381.
8. Anderson JB, Foglio A, Harrant AB, et al. Scoping review of therapeutic strategies for keloids and hypertrophic scars. Plast Reconstr Surg Glob Open. 2021;9:e3469.
9. De Faverney PM, Molamodi K, Tancrede-Bohin E, Verschoore M. Support for dermatological research in Sub-Saharan Africa: insights from African hair and skin research programs. Int J Dermatol. 2024;63:1081-8.
10. Nangole FW, Agak GW. Keloid pathophysiology: fibroblast or inflammatory disorders? JPRAS Open. 2019;22:44-54.
11. Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg. 2017;43:S3-S18.
12. Chike-Obi CJ, Cole PD, Brissett AE. Keloids: pathogenesis, clinical features, and management. Semin Plast Surg. 2009;23:178-84.
13. Brissett AE, Sherris DA. Scar contractures, hypertrophic scars, and keloids. Facial Plast Surg. 2001;17:263-72.
14. Zhou B, Gao Z, Liu W, Wu X, Wang W. Important role of mechanical microenvironment on macrophage dysfunction during keloid pathogenesis. Exp Dermatol. 2022;31:375-80.
15. Tsai CH, Ogawa R. Keloid research: current status and future directions. Scars Burn Heal. 2019;5:2059513119868659.
16. Ogawa R, Okai K, Tokumura F, et al. The relationship between skin stretching/contraction and pathologic scarring: the important role of mechanical forces in keloid generation. Wound Repair Regen. 2012;20:149-57.
17. Liu S, Yang H, Song J, Zhang Y, Abualhssain ATH, Yang B. Keloid: genetic susceptibility and contributions of genetics and epigenetics to its pathogenesis. Exp Dermatol. 2022;31:1665-75.
18. Kim HJ, Kim YH. Comprehensive insights into keloid pathogenesis and advanced therapeutic strategies. Int J Mol Sci. 2024;25:8776.
19. Mony MP, Harmon KA, Hess R, Dorafshar AH, Shafikhani SH. An updated review of hypertrophic scarring. Cells. 2023;12:678.
20. Limandjaja GC, Niessen FB, Scheper RJ, Gibbs S. Hypertrophic scars and keloids: overview of the evidence and practical guide for differentiating between these abnormal scars. Exp Dermatol. 2021;30:146-61.
21. Choi C, Mukovozov I, Jazdarehee A, et al. Management of hypertrophic scars in adults: a systematic review and meta-analysis. Australas J Dermatol. 2022;63:172-89.
22. Bailey J, Schwehr M, Beattie A. Management of keloids and hypertrophic scars. Am Fam Physician. 2024;110:605-11.
23. Elsaie ML. Update on management of keloid and hypertrophic scars: a systemic review. J Cosmet Dermatol. 2021;20:2729-38.
24. Peña OA, Martin P. Cellular and molecular mechanisms of skin wound healing. Nat Rev Mol Cell Biol. 2024;25:599-616.
26. Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res. 2017;58:81-94.
27. Mouw JK, Ou G, Weaver VM. Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol. 2014;15:771-85.
28. Rousselle P, Montmasson M, Garnier C. Extracellular matrix contribution to skin wound re-epithelialization. Matrix Biol. 2019;75-76:12-26.
29. Pakyari M, Farrokhi A, Maharlooei MK, Ghahary A. Critical role of transforming growth factor beta in different phases of wound healing. Adv Wound Care. 2013;2:215-24.
30. Roberts AB, Flanders KC, Heine UI, et al. Transforming growth factor-beta: multifunctional regulator of differentiation and development. Philos Trans R Soc Lond B Biol Sci. 1990;327:145-54.
31. Juhl P, Bondesen S, Hawkins CL, et al. Dermal fibroblasts have different extracellular matrix profiles induced by TGF-β, PDGF and IL-6 in a model for skin fibrosis. Sci Rep. 2020;10:17300.
32. Fang X, Hu X, Zheng Z, et al. Smad interacting protein 1 influences transforming growth factor-β1/Smad signaling in extracellular matrix protein production and hypertrophic scar formation. J Mol Histol. 2019;50:503-14.
33. Desmoulière A, Chaponnier C, Gabbiani G. Tissue repair, contraction, and the myofibroblast. Wound Repair Regen. 2005;13:7-12.
34. Darby IA, Laverdet B, Bonté F, Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301-11.
35. Ibrahim MM, Chen L, Bond JE, et al. Myofibroblasts contribute to but are not necessary for wound contraction. Lab Invest. 2015;95:1429-38.
36. Barnes LA, Marshall CD, Leavitt T, et al. Mechanical forces in cutaneous wound healing: emerging therapies to minimize scar formation. Adv Wound Care. 2018;7:47-56.
37. Junker JP, Kratz C, Tollbäck A, Kratz G. Mechanical tension stimulates the transdifferentiation of fibroblasts into myofibroblasts in human burn scars. Burns. 2008;34:942-6.
38. Hosgood G. Stages of wound healing and their clinical relevance. Vet Clin North Am Small Anim Pract. 2006;36:667-85.
39. Rognoni E, Pisco AO, Hiratsuka T, et al. Fibroblast state switching orchestrates dermal maturation and wound healing. Mol Syst Biol. 2018;14:e8174.
40. Marshall CD, Hu MS, Leavitt T, Barnes LA, Lorenz HP, Longaker MT. Cutaneous scarring: basic science, current treatments, and future directions. Adv Wound Care. 2018;7:29-45.
41. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453:314-21.
42. Frech FS, Hernandez L, Urbonas R, Zaken GA, Dreyfuss I, Nouri K. Hypertrophic scars and keloids: advances in treatment and review of established therapies. Am J Clin Dermatol. 2023;24:225-45.
43. Betarbet U, Blalock TW. Keloids: a review of etiology, prevention, and treatment. J Clin aesthetic Dermatol. 2020;13:33-43.
44. Huang C, Quong WL, Kamii Y, Ogawa R. Ideal surgical incision lines minimizing tension: a proposal based on observations of hypertrophic scars and keloids. Plast Reconstr Surg Glob Open. 2025;13:e7344.
45. Wray RC. Force required for wound closure and scar appearance. Plast Reconstr Surg. 1983;72:380-2.
46. Gurtner GC, Dauskardt RH, Wong VW, et al. Improving cutaneous scar formation by controlling the mechanical environment: large animal and phase I studies. Ann Surg. 2011;254:217-25.
49. Berry CE, Downer M Jr, Morgan AG, et al. The effects of mechanical force on fibroblast behavior in cutaneous injury. Front Surg. 2023;10:1167067.
50. Halper J. Basic components of connective tissues and extracellular matrix: fibronectin, fibrinogen, laminin, elastin, fibrillins, fibulins, matrilins, tenascins and thrombospondins. Adv Exp Med Biol. 2021;1348:105-26.
51. Ma Y, Feng X, Rogers JA, Huang Y, Zhang Y. Design and application of ‘J-shaped’ stress-strain behavior in stretchable electronics: a review. Lab Chip. 2017;17:1689-704.
52. Ling S, Zhang Q, Kaplan DL, Omenetto F, Buehler MJ, Qin Z. Printing of stretchable silk membranes for strain measurements. Lab Chip. 2016;16:2459-66.
53. Fernandes MG, da Silva LP, Cerqueira MT, et al. Mechanomodulatory biomaterials prospects in scar prevention and treatment. Acta Biomater. 2022;150:22-33.
54. Kness-Knezinskis E, Sheckley M, Hostler AC, Mora Pinos MG, Chen K, Gurtner GC. Translational approaches manipulating mechanobiology to promote scarless healing in humans. J Plast Reconstr Aesthet Surg. 2026;112:25-33.
56. Wu C. Focal adhesion: a focal point in current cell biology and molecular medicine. Cell Adh Migr. 2007;1:13-8.
57. Tan X, Yan Y, Song B, Zhu S, Mei Q, Wu K. Focal adhesion kinase: from biological functions to therapeutic strategies. Exp Hematol Oncol. 2023;12:83.
58. Wong VW, Rustad KC, Akaishi S, et al. Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling. Nat Med. 2011;18:148-52.
59. Chen K, Kwon SH, Henn D, et al. Disrupting biological sensors of force promotes tissue regeneration in large organisms. Nat Commun. 2021;12:5256.
60. Chen K, Griffin M, Henn D, et al. Targeting circulating mechanoresponsive monocytes and macrophages to reduce fibrosis. Nat Biomed Eng. 2026;10:1247-62.
61. Wong VW, Beasley B, Zepeda J, et al. A mechanomodulatory device to minimize incisional scar formation. Adv Wound Care. 2013;2:185-94.
62. Ma K, Kwon SH, Padmanabhan J, et al. Controlled delivery of a focal adhesion kinase inhibitor results in accelerated wound closure with decreased scar formation. J Invest Dermatol. 2018;138:2452-60.
63. Chen K, Henn D, Januszyk M, et al. Disrupting mechanotransduction decreases fibrosis and contracture in split-thickness skin grafting. Sci Transl Med. 2022;14:eabj9152.
64. Kohlhauser M, Mayrhofer M, Kamolz LP, Smolle C. An update on molecular mechanisms of scarring-a narrative review. Int J Mol Sci. 2024;25:11579.
65. Hu HH, Chen DQ, Wang YN, et al. New insights into TGF-β/Smad signaling in tissue fibrosis. Chem Biol Interact. 2018;292:76-83.
66. Zhang T, Wang XF, Wang ZC, et al. Current potential therapeutic strategies targeting the TGF-β/Smad signaling pathway to attenuate keloid and hypertrophic scar formation. Biomed Pharmacother. 2020;129:110287.
67. Shi X, Young CD, Zhou H, Wang X. Transforming growth factor-β signaling in fibrotic diseases and cancer-associated fibroblasts. Biomolecules. 2020;10:1666.
68. Dobaczewski M, Bujak M, Li N, et al. Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circ Res. 2010;107:418-28.
69. Wipff PJ, Rifkin DB, Meister JJ, Hinz B. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J Cell Biol. 2007;179:1311-23.
70. Bao H, Jiang K, Meng K, et al. TGF-β2 induces proliferation and inhibits apoptosis of human Tenon capsule fibroblast by miR-26 and its targeting of CTGF. Biomed Pharmacother. 2018;104:558-65.
71. Jung SC, Kang D, Ko EA. Roles of PDGF/PDGFR signaling in various organs. Korean J Physiol Pharmacol. 2025;29:139-55.
73. Irma J, Kartasasmita AS, Kartiwa A, Irfani I, Rizki SA, Onasis S. From growth factors to structure: PDGF and TGF-β in granulation tissue formation. A literature review. J Cell Mol Med. 2025;29:e70374.
74. Rajkumar VS, Shiwen X, Bostrom M, et al. Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing. Am J Pathol. 2006;169:2254-65.
75. He X, Li Y, Deng B, et al. The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: mechanisms and therapeutic opportunities. Cell Prolif. 2022;55:e13275.
76. Zhao S, Liu H, Wang H, et al. Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway. Burns Trauma. 2024;12:tkad048.
77. Jere SW, Houreld NN, Abrahamse H. Role of the PI3K/AKT (mTOR and GSK3β) signalling pathway and photobiomodulation in diabetic wound healing. Cytokine Growth Factor Rev. 2019;50:52-9.
78. Teng Y, Fan Y, Ma J, et al. The PI3K/Akt pathway: emerging roles in skin homeostasis and a group of non-malignant skin disorders. Cells. 2021;10:1219.
79. Darby IA, Desmoulière A. Scar formation: cellular mechanisms. In: Téot L, Mustoe TA, Middelkoop E, Gauglitz GG, Editors. Textbook on scar management: state of the art management and emerging technologies. Cham (CH): Springer; 2020.
80. Bahar ME, Kim HJ, Kim DR. Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies. Signal Transduct Target Ther. 2023;8:455.
81. Umbarkar P, Tousif S, Singh AP, et al. Fibroblast GSK-3α promotes fibrosis via RAF-MEK-ERK pathway in the injured heart. Circ Res. 2022;131:620-36.
82. Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet‐derived growth factor in wound healing. J of Cellular Biochemistry. 1991;45:319-26.
84. Mascharak S, Griffin M, Talbott HE, et al. Inhibiting mechanotransduction prevents scarring and yields regeneration in a large animal model. Sci Transl Med. 2025;17:eadt6387.
85. Mascharak S, desJardins-Park HE, Davitt MF, et al. Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring. Science. 2021;372:eaba2374.
86. Mascharak S, Talbott HE, Januszyk M, et al. Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing. Cell Stem Cell. 2022;29:315-27.e6.
87. Jin X, Wang J, Cao R, Jiang D. Wnt signaling pathway: biological function, diseases, and therapeutic interventions. MedComm. 2026;7:e70580.
88. Mullin NK, Mallipeddi NV, Hamburg-Shields E, Ibarra B, Khalil AM, Atit RP. Wnt/β-catenin signaling pathway regulates specific lncRNAs that impact dermal fibroblasts and skin fibrosis. Front Genet. 2017;8:183.
89. Griffin MF, Huber J, Evan FJ, Quarto N, Longaker MT. The role of Wnt signaling in skin fibrosis. Med Res Rev. 2022;42:615-28.
90. Bielefeld KA, Amini-Nik S, Alman BA. Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol Life Sci. 2013;70:2059-81.
91. Hamburg-Shields E, DiNuoscio GJ, Mullin NK, Lafyatis R, Atit RP. Sustained β-catenin activity in dermal fibroblasts promotes fibrosis by up-regulating expression of extracellular matrix protein-coding genes. J Pathol. 2015;235:686-97.
92. Sato M. Upregulation of the Wnt/beta-catenin pathway induced by transforming growth factor-beta in hypertrophic scars and keloids. Acta Derm Venereol. 2006;86:300-7.
93. Premaraj S, Souza I, Premaraj T. Mechanical loading activates β-catenin signaling in periodontal ligament cells. Angle Orthod. 2011;81:592-9.
94. Mendez MG, Janmey PA. Transcription factor regulation by mechanical stress. Int J Biochem Cell Biol. 2012;44:728-32.
95. O’Reilly S, Crofton E, Brown J, Strong J, Ziviani J. Use of tape for the management of hypertrophic scar development: a comprehensive review. Scars Burn Heal. 2021;7:20595131211029206.
96. Kazmer DO, Eaves FF 3rd. Force modulating tissue bridges for reduction of tension and scar: finite element and image analysis of preclinical incisional and nonincisional models. Aesthet Surg J. 2018;38:1250-63.
97. Bleasdale B, Finnegan S, Murray K, Kelly S, Percival SL. The use of silicone adhesives for scar reduction. Adv Wound Care. 2015;4:422-30.
98. Block L, Gosain A, King TW. Emerging therapies for scar prevention. Adv Wound Care. 2015;4:607-14.
99. McPhail SM, Wiseman J, Simons M, Kimble R, Tyack Z. Cost-effectiveness of scar management post-burn: a trial-based economic evaluation of three intervention models. Sci Rep. 2022;12:18601.





