Research progress of therapeutic ultrasound in chronic wound healing_West China Medical Journal

Authors：

WANG Yuhong , LUO Kaixuan , WANG Bin , CHEN Moxian ,  AO Lijuan

School of Rehabilitation, Kunming Medical University, Kunming, Yunnan 650500, P. R. China;

Corresponding author：

AO Lijuan, Email: 13508710081@qq.com

Keywords：

Therapeutic ultrasound; Chronic wounds; Healing; Research progress

DOI：

10.7507/1002-0179.202011016

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Chronic wounds have a high incidence and a long course of disease, and will bring a heavy economic burden to patients, which is the difficulty of clinical treatment at present. Therefore, it is urgent to find an effective method to promote chronic wound healing. In recent years, the application of therapeutic ultrasound in chronic wound treatment has gradually gained attention, and has become a promising adjuvant therapy. This article reviews the process of wound healing, the mechanism of therapeutic ultrasound in promoting wound healing, the biological effects of therapeutic ultrasound in different stages of wound healing and its application in diabetic ulcer, venous ulcer of lower limbs and pressure ulcer, in order to provide new ideas and directions for the treatment of chronic wounds.

Citation： WANG Yuhong, LUO Kaixuan, WANG Bin, CHEN Moxian, AO Lijuan. Research progress of therapeutic ultrasound in chronic wound healing. West China Medical Journal, 2021, 36(10): 1460-1464. doi: 10.7507/1002-0179.202011016 Copy

1.	van Koppen CJ, Hartmann RW. Advances in the treatment of chronic wounds: a patent review. Expert Opin Ther Pat, 2015, 25(8): 931-937.
2.	Han G, Ceilley R. Chronic wound healing: a review of current management and treatments. Adv Ther, 2017, 34(3): 599-610.
3.	Pérez-Rafael S, Ivanova K, Stefanov I, et al. Nanoparticle-driven self-assembling injectable hydrogels provide a multi-factorial approach for chronic wound treatment. Acta Biomater, 2021, 13: S1742-7061(21)00451-7.
4.	Kumar A, Shukla U, Prabhakar T, et al. Hyperbaric oxygen therapy as an adjuvant to standard therapy in the treatment of diabetic foot ulcers. J Anaesthesiol Clin Pharmacol, 2020, 36(2): 213-218.
5.	Augustine R, Hasan A, Dalvi YB, et al. Growth factor loaded in situ photocrosslinkable poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/gelatin methacryloyl hybrid patch for diabetic wound healing. Mater Sci Eng C Mater Biol Appl, 2021, 118: 111519.
6.	Giri P, Krishnaraj B, Chandra Sistla S, et al. Does negative pressure wound therapy with saline instillation improve wound healing compared to conventional negative pressure wound therapy? - A randomized controlled trial in patients with extremity ulcers. Ann Med Surg (Lond), 2020, 61: 73-80.
7.	Vu NB, Nguyen HT, Palumbo R, et al. Stem cell-derived exosomes for wound healing: current status and promising directions. Minerva Med, 2021, 112(3): 384-400.
8.	Bajpai A, Nadkarni S, Neidrauer M, et al. Effects of non-thermal, non-cavitational ultrasound exposure on human diabetic ulcer healing and inflammatory gene expression in a pilot study. Ultrasound Med Biol, 2018, 44(9): 2043-2049.
9.	Samuels JA, Weingarten MS, Margolis DJ, et al. Low-frequency (< 100 kHz), low-intensity (< 100 mW/cm²) ultrasound to treat venous ulcers: a human study and in vitro experiments. J Acoust Soc Am, 2013, 134(2): 1541-1547.
10.	Bora Karsli P, Gurcay E, Karaahmet OZ, et al. High-voltage electrical stimulation versus ultrasound in the treatment of pressure ulcers. Adv Skin Wound Care, 2017, 30(12): 565-570.
11.	Qing C. The molecular biology in wound healing & non-healing wound. Chin J Traumatol, 2017, 20(4): 189-193.
12.	Eelen G, de Zeeuw P, Simons M, et al. Endothelial cell metabolism in normal and diseased vasculature. Circ Res, 2015, 116(7): 1231-1244.
13.	Raeder K, Jachan DE, Müller-Werdan U, et al. Prevalence and risk factors of chronic wounds in nursing homes in Germany: a cross-sectional study. Int Wound J, 2020, 17(5): 1128-1134.
14.	Conner-Kerr T, Oesterle ME. Current perspectives on therapeutic ultrasound in the management of chronic wounds: a review of evidence. Chroni Wound Care Manag Res, 2017, 4: 89-98.
15.	Martínez-Fernández R, Máñez-Miró JU, Rodríguez-Rojas R, et al. Randomized trial of focused ultrasound subthalamotomy for Parkinson’s disease. N Engl J Med, 2020, 383(26): 2501-2513.
16.	Gibbons GW, Orgill DP, Serena TE, et al. A prospective, randomized, controlled trial comparing the effects of noncontact, low-frequency ultrasound to standard care in healing venous leg ulcers. Ostomy Wound Manage, 2015, 61(1): 16-29.
17.	Yao M, Hasturk H, Kantarci A, et al. A pilot study evaluating non-contact low-frequency ultrasound and underlying molecular mechanism on diabetic foot ulcers. Int Wound J, 2014, 11(6): 586-593.
18.	Bretsztajn L, Gedroyc W. Brain-focussed ultrasound: what’s the “FUS” all about? A review of current and emerging neurological applications. Br J Radiol, 2018, 91(1087): 20170481.
19.	燕铁斌. 物理治疗学. 3版. 北京: 人民卫生出版社, 2019: 436-445.
20.	Mauri G, Nicosia L, Xu Z, et al. Focused ultrasound: tumour ablation and its potential to enhance immunological therapy to cancer. Br J Radiol, 2018, 91(1083): 20170641.
21.	Sussman C, Bates-Jensen BM. Wound care: a collaborative practice manual for health professionals. Philadelphia: Lippincott Williams & Wilkins, 2012: 56-99.
22.	Zhou S, Bachem MG, Seufferlein T, et al. Low intensity pulsed ultrasound accelerates macrophage phagocytosis by a pathway that requires actin polymerization, Rho, and Src/MAPKs activity. Cell Signal, 2008, 20(4): 695-704.
23.	Wiegand C, Bittenger K, Galiano RD, et al. Does noncontact low-frequency ultrasound therapy contribute to wound healing at the molecular level?. Wound Repair Regen, 2017, 25(5): 871-882.
24.	Roper JA, Williamson RC, Bally B, et al. Ultrasonic stimulation of mouse skin reverses the healing delays in diabetes and aging by activation of Rac1. J Invest Dermatol, 2015, 135(11): 2842-2851.
25.	Shabestani Monfared G, Ertl P, Rothbauer M. An on-chip wound healing assay fabricated by xurography for evaluation of dermal fibroblast cell migration and wound closure. Sci Rep, 2020, 10(1): 16192.
26.	Maeshige N, Terashi H, Aoyama M, et al. Effect of ultrasound irradiation on α-SMA and TGF-β1 expression in human dermal fibroblasts. Kobe J Med Sci, 2011, 56(6): E242-E252.
27.	Hazlewood D, Feng Y, Lu Q, et al. Treatment of post-traumatic joint contracture in a rabbit model using pulsed, high intensity laser and ultrasound. Phys Med Biol, 2018, 63(20): 205009.
28.	Conner-Kerr T, Malpass G, Steele A, et al. Effects of 35 kHz, low-frequency ultrasound application in vitro on human fibroblast morphology and migration patterns. Ostomy Wound Manage, 2015, 61(3): 34-41.
29.	Mesquita RL, Silva PI, Melo e Silva SH, et al. Effect of low-intensity therapeutic ultrasound on wound healing in rats subjected to third-degree burns. Acta Cir Bras, 2016, 31(1): 36-43.
30.	Chen L, Zheng Q, Chen X, et al. Low-frequency ultrasound enhances vascular endothelial growth factor expression, thereby promoting the wound healing in diabetic rats. Exp Ther Med, 2019, 18(5): 4040-4048.
31.	Maan ZN, Januszyk M, Rennert RC, et al. Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice. Plast Reconstr Surg, 2014, 134(3): 402e-411e.
32.	Yan J, Tie G, Wang S, et al. Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages. Nat Commun, 2018, 9(1): 33.
33.	Dyson M, Franks C, Suckling J. Stimulation of healing of varicose ulcers by ultrasound. Ultrasonics, 1976, 14(5): 232-236.
34.	Peschen M, Weichenthal M, Schöpf E, et al. Low-frequency ultrasound treatment of chronic venous leg ulcers in an outpatient therapy. Acta Derm Venereol, 1997, 77(4): 311-314.
35.	Couch KS, Corbett L, Gould L, et al. The international consolidated venous ulcer guideline update 2015: process improvement, evidence analysis, and future goals. Ostomy Wound Manage, 2017, 63(5): 42-46.
36.	Honaker JS, Forston MR, Davis EA, et al. The effect of adjunctive noncontact low frequency ultrasound on deep tissue pressure injury. Wound Repair Regen, 2016, 24(6): 1081-1088.
37.	Polak A, Taradaj J, Nawrat-Szoltysik A, et al. Reduction of pressure ulcer size with high-voltage pulsed current and high-frequency ultrasound: a randomised trial. J Wound Care, 2016, 25(12): 742-754.
38.	Alkahtani SA, Kunwar PS, Jalilifar M, et al. Ultrasound-based techniques as alternative treatments for chronic wounds: a comprehensive review of clinical applications. Cureus, 2017, 9(12): e1952.
39.	Blanco M, Bencivenga M, Jensen L. Effectiveness of 3 Mhz ultrasound in pediatric patients with scars, sequels of 2nd to 3rd degree burns. Plastic Surgery Rehabilitation Area of Children Hospital, Cordoba, Argentina: 2006-2012. Rev Bras Queimaduras, 2013, 12(2): 77-82.
40.	Ayan I, Aslan G, Cömelekoğlu U, et al. The effect of low-intensity pulsed sound waves delivered by the Exogen device on Staphylococcus aureus morphology and genetics. Acta Orthop Traumatol Turc, 2008, 42(4): 272-277.
41.	Durham PG, Sidders AE, Beam JE, et al. Harnessing ultrasound-stimulated phase change contrast agents to improve antibiotic efficacy against methicillin-resistant Staphylococcus aureus biofilms. Biofilm, 2021, 3: 100049.

1. van Koppen CJ, Hartmann RW. Advances in the treatment of chronic wounds: a patent review. Expert Opin Ther Pat, 2015, 25(8): 931-937.
2. Han G, Ceilley R. Chronic wound healing: a review of current management and treatments. Adv Ther, 2017, 34(3): 599-610.
3. Pérez-Rafael S, Ivanova K, Stefanov I, et al. Nanoparticle-driven self-assembling injectable hydrogels provide a multi-factorial approach for chronic wound treatment. Acta Biomater, 2021, 13: S1742-7061(21)00451-7.
4. Kumar A, Shukla U, Prabhakar T, et al. Hyperbaric oxygen therapy as an adjuvant to standard therapy in the treatment of diabetic foot ulcers. J Anaesthesiol Clin Pharmacol, 2020, 36(2): 213-218.
5. Augustine R, Hasan A, Dalvi YB, et al. Growth factor loaded in situ photocrosslinkable poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/gelatin methacryloyl hybrid patch for diabetic wound healing. Mater Sci Eng C Mater Biol Appl, 2021, 118: 111519.
6. Giri P, Krishnaraj B, Chandra Sistla S, et al. Does negative pressure wound therapy with saline instillation improve wound healing compared to conventional negative pressure wound therapy? - A randomized controlled trial in patients with extremity ulcers. Ann Med Surg (Lond), 2020, 61: 73-80.
7. Vu NB, Nguyen HT, Palumbo R, et al. Stem cell-derived exosomes for wound healing: current status and promising directions. Minerva Med, 2021, 112(3): 384-400.
8. Bajpai A, Nadkarni S, Neidrauer M, et al. Effects of non-thermal, non-cavitational ultrasound exposure on human diabetic ulcer healing and inflammatory gene expression in a pilot study. Ultrasound Med Biol, 2018, 44(9): 2043-2049.
9. Samuels JA, Weingarten MS, Margolis DJ, et al. Low-frequency (< 100 kHz), low-intensity (< 100 mW/cm²) ultrasound to treat venous ulcers: a human study and in vitro experiments. J Acoust Soc Am, 2013, 134(2): 1541-1547.
10. Bora Karsli P, Gurcay E, Karaahmet OZ, et al. High-voltage electrical stimulation versus ultrasound in the treatment of pressure ulcers. Adv Skin Wound Care, 2017, 30(12): 565-570.
11. Qing C. The molecular biology in wound healing & non-healing wound. Chin J Traumatol, 2017, 20(4): 189-193.
12. Eelen G, de Zeeuw P, Simons M, et al. Endothelial cell metabolism in normal and diseased vasculature. Circ Res, 2015, 116(7): 1231-1244.
13. Raeder K, Jachan DE, Müller-Werdan U, et al. Prevalence and risk factors of chronic wounds in nursing homes in Germany: a cross-sectional study. Int Wound J, 2020, 17(5): 1128-1134.
14. Conner-Kerr T, Oesterle ME. Current perspectives on therapeutic ultrasound in the management of chronic wounds: a review of evidence. Chroni Wound Care Manag Res, 2017, 4: 89-98.
15. Martínez-Fernández R, Máñez-Miró JU, Rodríguez-Rojas R, et al. Randomized trial of focused ultrasound subthalamotomy for Parkinson’s disease. N Engl J Med, 2020, 383(26): 2501-2513.
16. Gibbons GW, Orgill DP, Serena TE, et al. A prospective, randomized, controlled trial comparing the effects of noncontact, low-frequency ultrasound to standard care in healing venous leg ulcers. Ostomy Wound Manage, 2015, 61(1): 16-29.
17. Yao M, Hasturk H, Kantarci A, et al. A pilot study evaluating non-contact low-frequency ultrasound and underlying molecular mechanism on diabetic foot ulcers. Int Wound J, 2014, 11(6): 586-593.
18. Bretsztajn L, Gedroyc W. Brain-focussed ultrasound: what’s the “FUS” all about? A review of current and emerging neurological applications. Br J Radiol, 2018, 91(1087): 20170481.
19. 燕铁斌. 物理治疗学. 3版. 北京: 人民卫生出版社, 2019: 436-445.
20. Mauri G, Nicosia L, Xu Z, et al. Focused ultrasound: tumour ablation and its potential to enhance immunological therapy to cancer. Br J Radiol, 2018, 91(1083): 20170641.
21. Sussman C, Bates-Jensen BM. Wound care: a collaborative practice manual for health professionals. Philadelphia: Lippincott Williams & Wilkins, 2012: 56-99.
22. Zhou S, Bachem MG, Seufferlein T, et al. Low intensity pulsed ultrasound accelerates macrophage phagocytosis by a pathway that requires actin polymerization, Rho, and Src/MAPKs activity. Cell Signal, 2008, 20(4): 695-704.
23. Wiegand C, Bittenger K, Galiano RD, et al. Does noncontact low-frequency ultrasound therapy contribute to wound healing at the molecular level?. Wound Repair Regen, 2017, 25(5): 871-882.
24. Roper JA, Williamson RC, Bally B, et al. Ultrasonic stimulation of mouse skin reverses the healing delays in diabetes and aging by activation of Rac1. J Invest Dermatol, 2015, 135(11): 2842-2851.
25. Shabestani Monfared G, Ertl P, Rothbauer M. An on-chip wound healing assay fabricated by xurography for evaluation of dermal fibroblast cell migration and wound closure. Sci Rep, 2020, 10(1): 16192.
26. Maeshige N, Terashi H, Aoyama M, et al. Effect of ultrasound irradiation on α-SMA and TGF-β1 expression in human dermal fibroblasts. Kobe J Med Sci, 2011, 56(6): E242-E252.
27. Hazlewood D, Feng Y, Lu Q, et al. Treatment of post-traumatic joint contracture in a rabbit model using pulsed, high intensity laser and ultrasound. Phys Med Biol, 2018, 63(20): 205009.
28. Conner-Kerr T, Malpass G, Steele A, et al. Effects of 35 kHz, low-frequency ultrasound application in vitro on human fibroblast morphology and migration patterns. Ostomy Wound Manage, 2015, 61(3): 34-41.
29. Mesquita RL, Silva PI, Melo e Silva SH, et al. Effect of low-intensity therapeutic ultrasound on wound healing in rats subjected to third-degree burns. Acta Cir Bras, 2016, 31(1): 36-43.
30. Chen L, Zheng Q, Chen X, et al. Low-frequency ultrasound enhances vascular endothelial growth factor expression, thereby promoting the wound healing in diabetic rats. Exp Ther Med, 2019, 18(5): 4040-4048.
31. Maan ZN, Januszyk M, Rennert RC, et al. Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice. Plast Reconstr Surg, 2014, 134(3): 402e-411e.
32. Yan J, Tie G, Wang S, et al. Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages. Nat Commun, 2018, 9(1): 33.
33. Dyson M, Franks C, Suckling J. Stimulation of healing of varicose ulcers by ultrasound. Ultrasonics, 1976, 14(5): 232-236.
34. Peschen M, Weichenthal M, Schöpf E, et al. Low-frequency ultrasound treatment of chronic venous leg ulcers in an outpatient therapy. Acta Derm Venereol, 1997, 77(4): 311-314.
35. Couch KS, Corbett L, Gould L, et al. The international consolidated venous ulcer guideline update 2015: process improvement, evidence analysis, and future goals. Ostomy Wound Manage, 2017, 63(5): 42-46.
36. Honaker JS, Forston MR, Davis EA, et al. The effect of adjunctive noncontact low frequency ultrasound on deep tissue pressure injury. Wound Repair Regen, 2016, 24(6): 1081-1088.
37. Polak A, Taradaj J, Nawrat-Szoltysik A, et al. Reduction of pressure ulcer size with high-voltage pulsed current and high-frequency ultrasound: a randomised trial. J Wound Care, 2016, 25(12): 742-754.
38. Alkahtani SA, Kunwar PS, Jalilifar M, et al. Ultrasound-based techniques as alternative treatments for chronic wounds: a comprehensive review of clinical applications. Cureus, 2017, 9(12): e1952.
39. Blanco M, Bencivenga M, Jensen L. Effectiveness of 3 Mhz ultrasound in pediatric patients with scars, sequels of 2nd to 3rd degree burns. Plastic Surgery Rehabilitation Area of Children Hospital, Cordoba, Argentina: 2006-2012. Rev Bras Queimaduras, 2013, 12(2): 77-82.
40. Ayan I, Aslan G, Cömelekoğlu U, et al. The effect of low-intensity pulsed sound waves delivered by the Exogen device on Staphylococcus aureus morphology and genetics. Acta Orthop Traumatol Turc, 2008, 42(4): 272-277.
41. Durham PG, Sidders AE, Beam JE, et al. Harnessing ultrasound-stimulated phase change contrast agents to improve antibiotic efficacy against methicillin-resistant Staphylococcus aureus biofilms. Biofilm, 2021, 3: 100049.

Previous Article
Research status of influencing factors of fear of disease progression in cancer patients
Next Article
Feasibility analysis of tuberculosis screening in diabetes mellitus patients in community

West China Medical Journal

Research progress of therapeutic ultrasound in chronic wound healing

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content