The application of nanoparticles in the treatment and prevention of pathological scars_Journal of Biomedical Engineering

Authors：

HUANG Yixi ^1,2 , ZHAO Lei ¹ ,  JIN Zhehu ¹ ,  CUI Aili ²

1. Department of Dermatology, Yanbian University Hospital, Yanji, Jilin 133000, P. R. China;
2. Department of Medical cosmetology, Yanbian University Hospital, Yanji, Jilin 133000, P. R. China;

Corresponding?author：

Keywords：

Nanoparticles; Drug delivery; Keloids; Hypertrophic scars; Pathological scars

DOI：

10.7507/1001-5515.202504070

Video：

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Pathological scars arise from abnormal repair of skin trauma and are associated with pain, pruritus, and cosmetic deformities, severely impairing patients' physical and mental well-being. Current clinical therapeutic strategies, including surgical excision, photodynamic therapy and pharmacotherapy, are associated with inherent limitations. In recent years, nanoparticle-based delivery systems, leveraging their advantages including small size, excellent biocompatibility, and robust targeting capability, have offered novel strategies for the prevention and treatment of pathological scars. These systems can either be used alone as functional components or serve as carriers to enable precise delivery of therapeutic agents to the epidermis or dermis. This article first introduces nanoparticles along with their classification and characteristics, then elaborates on the latest research progress of nanoparticles in the treatment and prevention of pathological scars, covering their single-agent applications and combination therapies. Finally, it discusses the potential application value of nanoparticles in achieving precise prevention and treatment of pathological scars, aiming to provide new insights for clinical translation.

Citation： HUANG Yixi, ZHAO Lei, JIN Zhehu, CUI Aili. The application of nanoparticles in the treatment and prevention of pathological scars. Journal of Biomedical Engineering, 2026, 43(2): 428-433. doi: 10.7507/1001-5515.202504070 Copy

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2.	Delaleu J, Charvet E, Petit A. Keloid disease: review with clinical atlas. part I: definitions, history, epidemiology, clinics and diagnosis. Ann Dermatol Venereol, 2023, 150(1): 3-15.
3.	Huang C, Ogawa R. Keloidal pathophysiology: current notions. Scars Burn Heal, 2021, 7: 2059513120980320.
4.	Ogawa R. The most current algorithms for the treatment and prevention of hypertrophic scars and keloids: a 2020 update of the algorithms published 10 years ago. Plast Reconstr Surg, 2022, 149(1): 79e-94e.
5.	張玉, 高亭亭, 金哲虎, 等. 治療瘢痕疙瘩的新型藥物遞送方式. 中國皮膚性病學雜志, 2024, 38(8): 827-832.
6.	Najahi-Missaoui W, Arnold R D, Cummings B S. Safe nanoparticles: are we there yet? Int J Mol Sci, 2020, 22(1): 385.
7.	Missaoui W N, Arnold R D, Cummings B S. Toxicological status of nanoparticles: what we know and what we don't know. Chem Biol Interact, 2018, 295: 1-12.
8.	Kam K R, Walsh L A, Bock S M, et al. The effect of nanotopography on modulating protein adsorption and the fibrotic response. Tissue Eng Part A, 2014, 20(1-2): 130-138.
9.	Mitchell M J, Billingsley M M, Haley R M, et al. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov, 2021, 20(2): 101-124.
10.	Eygeris Y, Gupta M, Kim J, et al. Chemistry of lipid nanoparticles for RNA delivery. Acc Chem Res, 2022, 55(1): 2-12.
11.	Golestani P. Lipid-based nanoparticles as a promising treatment for the skin cancer. Heliyon, 2024, 10(9): e29898.
12.	Beach M A, Nayanathara U, Gao Y, et al. Polymeric nanoparticles for drug delivery. Chem Rev, 2024, 124(9): 5505-5616.
13.	Kumar L, Kukreti G, Rana R, et al. Poly(lactic-co-glycolic) acid (PLGA) nanoparticles and transdermal drug delivery: an overview. Curr Pharm Des, 2023, 29(37): 2940-2953.
14.	Venditti I. Engineered gold-based nanomaterials: morphologies and functionalities in biomedical applications: a mini review. Bioengineering, 2019, 6(2): 53.
15.	Medici S, Peana M, Coradduzza D, et al. Gold nanoparticles and cancer: detection, diagnosis and therapy. Semin Cancer Biol, 2021, 76: 27-37.
16.	Faghani G, Azarniya A. Emerging nanomaterials for novel wound dressings: from metallic nanoparticles and MXene nanosheets to metal-organic frameworks. Heliyon, 2024, 10(21): e39611.
17.	Giri V P, Pandey S, Kumari M, et al. Biogenic silver nanoparticles as a more efficient contrivance for wound healing acceleration than common antiseptic medicine. FEMS Microbiol Lett, 2019, 366(16): fnz201.
18.	Xu M, Wei S, Duan L, et al. The recent advancements in protein nanoparticles for immunotherapy. Nanoscale, 2024, 16(25): 11825-11848.
19.	Martínez-López A L, Pangua C, Reboredo C, et al. Protein-based nanoparticles for drug delivery purposes. Int J Pharm, 2020, 581: 119289.
20.	Cheng K, Kang Q, Zhao X. Biogenic nanoparticles as immunomodulator for tumor treatment. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2020, 12(6): e1646.
21.	Knoedler S, Broichhausen S, Guo R, et al. Fibroblasts-the cellular choreographers of wound healing. Front Immunol, 2023, 14: 1233800.
22.	Xiao Y, Xu D, Song H, et al. Cuprous oxide nanoparticles reduces hypertrophic scarring by inducing fibroblast apoptosis. Int J Nanomedicine, 2019, 14: 5989-6000.
23.	Kwan K H, Liu X, To M K, et al. Modulation of collagen alignment by silver nanoparticles results in better mechanical properties in wound healing. Nanomedicine, 2011, 7(4): 497-504.
24.	Zhang Q, Shi L, He H, et al. Down-regulating scar formation by microneedles directly via a mechanical communication pathway. ACS Nano, 2022, 16(7): 10163-10178.
25.	Chun Y Y, Tan W W R, Vos M I G, et al. Scar prevention through topical delivery of gelatin-tyramine-siSPARC nanoplex loaded in dissolvable hyaluronic acid microneedle patch across skin barrier. Biomater Sci, 2022, 10(14): 3963-3971.
26.	Park J, Kim Y C. Topical delivery of 5-fluorouracil-loaded carboxymethyl chitosan nanoparticles using microneedles for keloid treatment. Drug Deliv Transl Res, 2021, 11(1): 205-213.
27.	Wu Z, Huang D, Xie J, et al. Triamcinolone acetonide suppressed scar formation in mice and human hypertrophic scar fibroblasts in a dose-dependent manner. Cell Mol Biol, 2023, 69(8): 226-231.
28.	Qin Z, Chen F, Chen D, et al. Transdermal permeability of triamcinolone acetonide lipid nanoparticles. Int J Nanomedicine, 2019, 14: 2485-2495.
29.	Wang P, Peng Z, Yu L, et al. Verteporfin-loaded bioadhesive nanoparticles for the prevention of hypertrophic scar. Small Methods, 2024, 8(8): e2301295.
30.	Yuan R, Dai X, Li Y, et al. Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-β2/Smad3 signaling. Mol Med Rep, 2021, 24(5): 758.
31.	Meng S, Wei Q, Chen S, et al. Mir-141-3p-functionalized exosomes loaded in dissolvable microneedle arrays for hypertrophic scar treatment. Small, 2024, 20(8): e2305374.
32.	Li L, Wang Y, Meng J, et al. Sele-targeted siRNA liposome nanoparticles inhibit pathological scars formation via blocking the cross-talk between monocyte and endothelial cells: a preclinical study based on a novel mice scar model. J Nanobiotechnology, 2024, 22(1): 733.
33.	Martins W K, Belotto R, Silva M N, et al. Autophagy regulation and photodynamic therapy: insights to improve outcomes of cancer treatment. Front Oncol, 2020, 10: 610472.
34.	Chen Z, Gao J, Li L. New challenges in scar therapy: the novel scar therapy strategies based on nanotechnology. Nanomedicine, 2024, 19(28): 2413-2432.
35.	Yu Z, Meng X, Zhang S, et al. IR-808 loaded nanoethosomes for aggregation-enhanced synergistic transdermal photodynamic/photothermal treatment of hypertrophic scars. Biomater Sci, 2022, 10(1): 158-166.
36.	Chen Y, Zhang Z, Xin Y, et al. Functional transdermal nanoethosomes enhance photodynamic therapy of hypertrophic scars via self-generating oxygen. ACS Appl Mater Interfaces, 2021, 13(7): 7955-7965.
37.	Rahimnejad M, Derakhshanfar S, Zhong W. Biomaterials and tissue engineering for scar management in wound care. Burns Trauma, 2017, 5: 4.
38.	Wu W M, Ma X, Fan L. Accelerating dermal wound healing and mitigating excessive scar formation using LBL modified nanofibrous mats. Mater Des, 2020, 185: 108265.
39.	Zhang D P, Li L J, Shan Y H, et al. In vivo study of silk fibroin/gelatin electrospun nanofiber dressing loaded with astragaloside IV on the effect of promoting wound healing and relieving scar. J Drug Deliv Sci Technol, 2019, 52: 272-281.
40.	Carney B C, Chen J H, Kent R A, et al. Reactive oxygen species scavenging potential contributes to hypertrophic scar formation. J Surg Res, 2019, 244: 312-323.
41.	He J, Meng X, Meng C, et al. Layer-by-Layer pirfenidone/cerium oxide nanocapsule dressing promotes wound repair and prevents scar formation. Molecules, 2022, 27(6): 1830.
42.	Liang J, Zeng H, Qiao L, et al. 3D printed piezoelectric wound dressing with dual piezoelectric response models for scar-prevention wound healing. ACS Appl Mater Interfaces, 2022, 14(27): 30507-30522.

1. Ogawa R, Dohi T, Tosa M, et al. The latest strategy for keloid and hypertrophic scar prevention and treatment: the Nippon Medical School (NMS) protocol. J Nippon Med Sch, 2021, 88(1): 2-9.
2. Delaleu J, Charvet E, Petit A. Keloid disease: review with clinical atlas. part I: definitions, history, epidemiology, clinics and diagnosis. Ann Dermatol Venereol, 2023, 150(1): 3-15.
3. Huang C, Ogawa R. Keloidal pathophysiology: current notions. Scars Burn Heal, 2021, 7: 2059513120980320.
4. Ogawa R. The most current algorithms for the treatment and prevention of hypertrophic scars and keloids: a 2020 update of the algorithms published 10 years ago. Plast Reconstr Surg, 2022, 149(1): 79e-94e.
5. 張玉, 高亭亭, 金哲虎, 等. 治療瘢痕疙瘩的新型藥物遞送方式. 中國皮膚性病學雜志, 2024, 38(8): 827-832.
6. Najahi-Missaoui W, Arnold R D, Cummings B S. Safe nanoparticles: are we there yet? Int J Mol Sci, 2020, 22(1): 385.
7. Missaoui W N, Arnold R D, Cummings B S. Toxicological status of nanoparticles: what we know and what we don't know. Chem Biol Interact, 2018, 295: 1-12.
8. Kam K R, Walsh L A, Bock S M, et al. The effect of nanotopography on modulating protein adsorption and the fibrotic response. Tissue Eng Part A, 2014, 20(1-2): 130-138.
9. Mitchell M J, Billingsley M M, Haley R M, et al. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov, 2021, 20(2): 101-124.
10. Eygeris Y, Gupta M, Kim J, et al. Chemistry of lipid nanoparticles for RNA delivery. Acc Chem Res, 2022, 55(1): 2-12.
11. Golestani P. Lipid-based nanoparticles as a promising treatment for the skin cancer. Heliyon, 2024, 10(9): e29898.
12. Beach M A, Nayanathara U, Gao Y, et al. Polymeric nanoparticles for drug delivery. Chem Rev, 2024, 124(9): 5505-5616.
13. Kumar L, Kukreti G, Rana R, et al. Poly(lactic-co-glycolic) acid (PLGA) nanoparticles and transdermal drug delivery: an overview. Curr Pharm Des, 2023, 29(37): 2940-2953.
14. Venditti I. Engineered gold-based nanomaterials: morphologies and functionalities in biomedical applications: a mini review. Bioengineering, 2019, 6(2): 53.
15. Medici S, Peana M, Coradduzza D, et al. Gold nanoparticles and cancer: detection, diagnosis and therapy. Semin Cancer Biol, 2021, 76: 27-37.
16. Faghani G, Azarniya A. Emerging nanomaterials for novel wound dressings: from metallic nanoparticles and MXene nanosheets to metal-organic frameworks. Heliyon, 2024, 10(21): e39611.
17. Giri V P, Pandey S, Kumari M, et al. Biogenic silver nanoparticles as a more efficient contrivance for wound healing acceleration than common antiseptic medicine. FEMS Microbiol Lett, 2019, 366(16): fnz201.
18. Xu M, Wei S, Duan L, et al. The recent advancements in protein nanoparticles for immunotherapy. Nanoscale, 2024, 16(25): 11825-11848.
19. Martínez-López A L, Pangua C, Reboredo C, et al. Protein-based nanoparticles for drug delivery purposes. Int J Pharm, 2020, 581: 119289.
20. Cheng K, Kang Q, Zhao X. Biogenic nanoparticles as immunomodulator for tumor treatment. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2020, 12(6): e1646.
21. Knoedler S, Broichhausen S, Guo R, et al. Fibroblasts-the cellular choreographers of wound healing. Front Immunol, 2023, 14: 1233800.
22. Xiao Y, Xu D, Song H, et al. Cuprous oxide nanoparticles reduces hypertrophic scarring by inducing fibroblast apoptosis. Int J Nanomedicine, 2019, 14: 5989-6000.
23. Kwan K H, Liu X, To M K, et al. Modulation of collagen alignment by silver nanoparticles results in better mechanical properties in wound healing. Nanomedicine, 2011, 7(4): 497-504.
24. Zhang Q, Shi L, He H, et al. Down-regulating scar formation by microneedles directly via a mechanical communication pathway. ACS Nano, 2022, 16(7): 10163-10178.
25. Chun Y Y, Tan W W R, Vos M I G, et al. Scar prevention through topical delivery of gelatin-tyramine-siSPARC nanoplex loaded in dissolvable hyaluronic acid microneedle patch across skin barrier. Biomater Sci, 2022, 10(14): 3963-3971.
26. Park J, Kim Y C. Topical delivery of 5-fluorouracil-loaded carboxymethyl chitosan nanoparticles using microneedles for keloid treatment. Drug Deliv Transl Res, 2021, 11(1): 205-213.
27. Wu Z, Huang D, Xie J, et al. Triamcinolone acetonide suppressed scar formation in mice and human hypertrophic scar fibroblasts in a dose-dependent manner. Cell Mol Biol, 2023, 69(8): 226-231.
28. Qin Z, Chen F, Chen D, et al. Transdermal permeability of triamcinolone acetonide lipid nanoparticles. Int J Nanomedicine, 2019, 14: 2485-2495.
29. Wang P, Peng Z, Yu L, et al. Verteporfin-loaded bioadhesive nanoparticles for the prevention of hypertrophic scar. Small Methods, 2024, 8(8): e2301295.
30. Yuan R, Dai X, Li Y, et al. Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-β2/Smad3 signaling. Mol Med Rep, 2021, 24(5): 758.
31. Meng S, Wei Q, Chen S, et al. Mir-141-3p-functionalized exosomes loaded in dissolvable microneedle arrays for hypertrophic scar treatment. Small, 2024, 20(8): e2305374.
32. Li L, Wang Y, Meng J, et al. Sele-targeted siRNA liposome nanoparticles inhibit pathological scars formation via blocking the cross-talk between monocyte and endothelial cells: a preclinical study based on a novel mice scar model. J Nanobiotechnology, 2024, 22(1): 733.
33. Martins W K, Belotto R, Silva M N, et al. Autophagy regulation and photodynamic therapy: insights to improve outcomes of cancer treatment. Front Oncol, 2020, 10: 610472.
34. Chen Z, Gao J, Li L. New challenges in scar therapy: the novel scar therapy strategies based on nanotechnology. Nanomedicine, 2024, 19(28): 2413-2432.
35. Yu Z, Meng X, Zhang S, et al. IR-808 loaded nanoethosomes for aggregation-enhanced synergistic transdermal photodynamic/photothermal treatment of hypertrophic scars. Biomater Sci, 2022, 10(1): 158-166.
36. Chen Y, Zhang Z, Xin Y, et al. Functional transdermal nanoethosomes enhance photodynamic therapy of hypertrophic scars via self-generating oxygen. ACS Appl Mater Interfaces, 2021, 13(7): 7955-7965.
37. Rahimnejad M, Derakhshanfar S, Zhong W. Biomaterials and tissue engineering for scar management in wound care. Burns Trauma, 2017, 5: 4.
38. Wu W M, Ma X, Fan L. Accelerating dermal wound healing and mitigating excessive scar formation using LBL modified nanofibrous mats. Mater Des, 2020, 185: 108265.
39. Zhang D P, Li L J, Shan Y H, et al. In vivo study of silk fibroin/gelatin electrospun nanofiber dressing loaded with astragaloside IV on the effect of promoting wound healing and relieving scar. J Drug Deliv Sci Technol, 2019, 52: 272-281.
40. Carney B C, Chen J H, Kent R A, et al. Reactive oxygen species scavenging potential contributes to hypertrophic scar formation. J Surg Res, 2019, 244: 312-323.
41. He J, Meng X, Meng C, et al. Layer-by-Layer pirfenidone/cerium oxide nanocapsule dressing promotes wound repair and prevents scar formation. Molecules, 2022, 27(6): 1830.
42. Liang J, Zeng H, Qiao L, et al. 3D printed piezoelectric wound dressing with dual piezoelectric response models for scar-prevention wound healing. ACS Appl Mater Interfaces, 2022, 14(27): 30507-30522.

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The application of nanoparticles in the treatment and prevention of pathological scars

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