Wound healing is the premise of body functional rehabilitation after trauma. If the wound is not treated in time, infection will occur. If the inflammatory process is excessive, the healing speed and quality will be affected. ω-3 polyunsaturated fatty acids (ω-3 PUFAs) play an important role in wound healing and tissue repair, which can inhibit the inflammatory response, promote angiogenesis, regulate the nervous system, control blood glucose levels, inhibit microbial growth, and accelerate wound healing. This review introduces the properties of ω-3 PUFAS and explored the healing mechanism of ω-3 PUFAS in promoting burn, traumatic brain injury wound, diabetic burn and diabetic foot ulcers and the routes of administration.

1.Sharifiaghdam M, shaabani E, Faridi-Majidi R, et al. Macrophages as a therapeutic target to promote diabetic wound healing[J]. Mol Ther, 2022, 30(9): 2891-2908. DOI: 10.1016/j.ymthe.2022.07.016.

2.Mascharak S, Talbott HE, Januszyk M, et al. Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing[J]. Cell Stem Cell, 2022, 29(2): 315-327. DOI: 10.1016/j.stem.2021.12.011.

3.Freedman BR, Hwang C, Talbot S, et al. Breakthrough treatments for accelerated wound healing[J]. Sci Adv, 2023, 9(20): eade7007. DOI: 10.1126/sciadv.ade7007.

4.Younes NB, Mohamed OA, Rizk NM. Docosahexaenoic acid counteracts the hypoxic-induced inflammatory and metabolic alterations in 3T3-L1 adipocytes[J]. Nutrients, 2022, 14(21): 4600. DOI: 10.3390/nu14214600.

5.Dissemond J, Romanelli M. Inflammatory skin diseases and wounds[J]. Br J Dermatol, 2022, 187(2): 167-177. DOI: 10.1111/bjd.21619.

6.Zhou C, Zhang B, Yang Y, et al. Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing[J]. Stem Cell Res Ther, 2023, 14(1): 107. DOI: 10.1186/s13287-023-03345-0.

7.Zhu W, Dong Y, Xu P, et al. A composite hydrogel containing resveratrol-laden nanoparticles and platelet-derived extracellular vesicles promotes wound healing in diabetic mice[J]. Acta Biomater, 2022, 154: 212-230. DOI: 10.1016/j.actbio.2022.10.038.

8.Willenborg S, Injarabian L, Eming SA. Role of macrophages in wound healing[J]. Cold Spring Harb Perspect Biol, 2022, 14(12): a041216. DOI: 10.1101/cshperspect.a041216.

9.Golanski J, Szymanska P, Rozalski M. Effects of omega-3 polyunsaturated fatty acids and their metabolites on haemostasis-current perspectives in cardiovascular disease[J]. Int J Mol Sci, 2021, 22(5): 2394. DOI: 10.3390/ijms22052394.

10.Kalupahana NS, Goonapienuwala BL, Moustaid-Moussa N. Omega-3 fatty acids and adipose tissue: inflammation and browning[J]. Annu Rev Nutr, 2020, 40: 25-49. DOI: 10.1146/annurev-nutr-122319-034142.

11.Djuricic I, Calder PC. Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: an update for 2021[J]. Nutrients, 2021, 13(7): 2421. DOI: 10.3390/nu13072421.

12.Lo Van A, Sakayori N, Hachem M, et al. Targeting the brain with a neuroprotective omega-3 fatty acid to enhance neurogenesis in hypoxic condition in culture[J]. Mol Neurobiol, 2019, 56(2): 986-999. DOI: 10.1007/s12035-018-1139-0.

13.Lo Van A, Hachem M, Lagarde M, et al. Omega-3 docosahexaenoic acid is a mediator of fate-decision of adult neural stem cells[J]. Int J Mol Sci, 2019, 20(17): 4240. DOI: 10.3390/ijms20174240.

14.Moriyama H, Endo J, Kataoka M, et al. Omega-3 fatty acid epoxides produced by PAF-AH2 in mast cells regulate pulmonary vascular remodeling[J]. Nat Commun, 2022, 13(1): 3013. DOI: 10.1038/s41467-022-30621-z.

15.Sivaraj D, Chen K, Chattopadhyay A, et al. Hydrogel scaffolds to deliver cell therapies for wound healing[J]. Front Bioeng Biotechnol, 2021, 9: 660145. DOI: 10.3389/fbioe.2021.660145.

16.Jakovija A, Chtanova T. Skin immunity in wound healing and cancer[J]. Front Immunol, 2023, 14: 1060258. DOI: 10.3389/fimmu.2023.1060258.

17.Fernández-Guarino M, Bacci S, Pérez González LA, et al. The role of physical therapies in wound healing and assisted scarring[J]. Int J Mol Sci, 2023, 24(8): 7487. DOI: 10.3390/ijms24087487.

18.Veith AP, Henderson K, Spencer A, et al. Therapeutic strategies for enhancing angiogenesis in wound healing[J]. Adv Drug Deliv Rev, 2019, 146: 97-125. DOI: 10.1016/j.addr.2018.09.010.

19.Duceac IA, Vereștiuc L, Coroaba A, et al. All-polysaccharide hydrogels for drug delivery applications: tunable chitosan beads surfaces via physical or chemical interactions, using oxidized pullulan[J]. Int J Biol Macromol, 2021, 181: 1047-1062. DOI: 10.1016/j.ijbiomac.2021.04.128.

20.Zhou X, Zhu X, Zeng H. Fatty acid metabolism in adaptive immunity[J]. FEBS J, 2023, 290(3): 584-599. DOI: 10.1111/febs.16296.

21.Kumar M, Pal N, Sharma P, et al. Omega-3 fatty acids and their interaction with the gut microbiome in the prevention and amelioration of type-2 diabetes[J]. Nutrients, 2022, 14(9): 1723. DOI: 10.3390/nu14091723.

22.von Schacky C. Omega-3 fatty acids in pregnancy-the case for a target omega-3 index[J]. Nutrients, 2020, 12(4): 898. DOI: 10.3390/nu12040898.

23.Troesch B, Eggersdorfer M, Laviano A, et al. Expert opinion on benefits of long-chain omega-3 fatty acids (DHA and EPA) in aging and clinical nutrition[J]. Nutrients, 2020, 12(9): 2555. DOI: 10.3390/nu12092555.

24.Weinberg RL, Brook RD, Rubenfire M, et al. Cardiovascular impact of nutritional supplementation with omega-3 fatty acids: JACC focus seminar[J]. J Am Coll Cardiol, 2021, 77(5): 593-608. DOI: 10.1016/j.jacc.2020.11.060.

25.Ogłuszka M, Lipiński P, Starzyński RR. Effect of omega-3 fatty acids on telomeres-are they the elixir of youth?[J]. Nutrients, 2022, 14(18): 3723. DOI: 10.3390/nu14183723.

26.Sawada Y, Saito-Sasaki N, Nakamura M. Omega 3 fatty acid and skin diseases[J]. Front Immunol, 2020, 11: 623052. DOI: 10.3389/fimmu.2020.623052.

27.Jiang H, Wang L, Wang D, et al. Omega-3 polyunsaturated fatty acid biomarkers and risk of type 2 diabetes, cardiovascular disease, cancer, and mortality[J]. Clin Nutr, 2022, 41(8): 1798-1807. DOI: 10.1016/j.clnu.2022.06.034.

28.Rodriguez D, Lavie CJ, Elagizi A, et al. Update on omega-3 polyunsaturated fatty acids on cardiovascular health[J]. Nutrients, 2022, 14(23): 5146. DOI: 10.3390/nu14235146.

29.Innes JK, Calder PC. Marine omega-3 (N-3) fatty acids for cardiovascular health: an update for 2020[J]. Int J Mol Sci, 2020, 21(4): 1362. DOI: 10.3390/ijms21041362.

30.Poggioli R, Hirani K, Jogani VG, et al. Modulation of inflammation and immunity by omega-3 fatty acids: a possible role for prevention and to halt disease progression in autoimmune, viral, and age-related disorders[J]. Eur Rev Med Pharmacol Sci, 2023, 27(15): 7380-7400. DOI: 10.26355/eurrev_202308_33310.

31.Ye L, He X, Obeng E, et al. The CuO and AgO co-modified ZnO nanocomposites for promoting wound healing in Staphylococcus aureus infection[J]. Mater Today Bio, 2023, 18: 100552. DOI: 10.1016/j.mtbio.2023.100552.

32.Ishihara T, Yoshida M, Arita M. Omega-3 fatty acid-derived mediators that control inflammation and tissue homeostasis[J]. Int Immunol, 2019, 31(9): 559-567. DOI: 10.1093/intimm/dxz001.

33.Antrum JHG, Galloway JE, Anwar MU, et al. Managing a small burn[J]. BMJ, 2022, 379: e068812. DOI: 10.1136/bmj-2021-068812.

34.Claes KEY, De Decker I, Blot S. Burn management: from survival to quality of survival[J]. Intensive Crit Care Nurs, 2023, 78: 103451. DOI: 10.1016/j.iccn.2023.103451.

35.Alipoor E, Jazayeri S, Dahmardehei M, et al. Effect of a collagen-enriched beverage with or without omega-3 fatty acids on wound healing, metabolic biomarkers, and adipokines in patients with major burns[J]. Clin Nutr, 2023, 42(3): 298-308. DOI: 10.1016/j.clnu.2022.12.014.

36.Tingö L, Hutchinson AN, Bergh C, et al. Potential modulation of inflammation by probiotic and omega-3 supplementation in elderly with chronic low-grade inflammation-a randomized, placebo-controlled trial[J]. Nutrients, 2022, 14(19): 3998. DOI: 10.3390/nu14193998.

37.Tihista S, Echavarría E. Effect of omega 3 polyunsaturated fatty acids derived from fish oil in major burn patients: a prospective randomized controlled pilot trial[J]. Clin Nutr, 2018, 37(1): 107-112. DOI: 10.1016/j.clnu.2017.01.002.

38.Nguyen QV, Malau-Aduli BS, Cavalieri J, et al. Enhancing omega-3 long-chain polyunsaturated fatty acid content of dairy-derived foods for human consumption[J]. Nutrients, 2019, 11(4): 743. DOI: 10.3390/nu11040743.

39.Lin L, Zheng S, Lai J, et al. Omega-3 polyunsaturated fatty acids protect neurological function after traumatic brain injury by suppressing microglial transformation to the proinflammatory phenotype and activating exosomal NGF/TrkA signaling[J]. Mol Neurobiol, 2023, 60(10): 5592-5606. DOI: 10.1007/s12035-023-03419-3.

40.Surowiecka A, Chrapusta A, Klimeczek-Chrapusta M, et al. Mesenchymal stem cells in burn wound management[J]. Int J Mol Sci, 2022, 23(23): 15339. DOI: 10.3390/ijms232315339.

41.Kamolz LP, Hecker A. Molecular mechanisms related to burns, burn wound healing and scarring[J]. Int J Mol Sci, 2023, 24(10): 8785. DOI: 10.3390/ijms24108785.

42.Wu X, He W, Mu X, et al. Macrophage polarization in diabetic wound healing[J]. Burns Trauma, 2022, 10: tkac051. DOI: 10.1093/burnst/tkac051.

43.Yeo HH, Shiau CW, Jao YH, et al. Rapid bactericidal activity of SC5005 combined with docosahexaenoic acid against multidrug-resistant staphylococcus aureus persisters and biofilms[J]. Antimicrob Agents Chemother, 2022, 66(12): e0080322. DOI: 10.1128/aac.00803-22.

44.McDermott K, Fang M, Boulton AJM, et al. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers[J]. Diabetes Care, 2023, 46(1): 209-221. DOI: 10.2337/dci22-0043.

45.Huang F, Lu X, Yang Y, et al. Microenvironment-based diabetic foot ulcer nanomedicine[J]. Adv Sci (Weinh), 2023, 10(2): e2203308. DOI: 10.1002/advs.202203308.

46.Lee TY, Yoon IJ, Han SK, et al. Skin hydration level cutoff value to predict wound healing potential in diabetic foot ulcers[J]. Diabetes Res Clin Pract, 2022, 193: 110122. DOI: 10.1016/j.diabres.2022.110122.

47.Li X, Jing X, Yu Z, Huang Y. Diverse antibacterial treatments beyond antibiotics for diabetic foot ulcer therapy[J]. Adv Healthc Mater, 2023, 12(23): e2300375. DOI: 10.1002/adhm.202300375.

48.Wang IE, Yi S, Block RC, et al. Aspirin and omega-3 polyunsaturated fatty acid use and their interaction in cardiovascular diseases and colorectal adenomas[J]. Nutr Res Rev, 2022, 35(2): 295-307. DOI: 10.1017/S0954422421000238.

49.Jia YC, Qiu S, Xu J, et al. Docosahexaenoic acid improves diabetic wound healing in a rat model by restoring impaired plasticity of macrophage progenitor cells[J]. Plast Reconstr Surg, 2020, 145(5): 942e-950e. DOI: 10.1097/PRS.0000000000006739.

50.Seth N, Chopra D, Lev-Tov H. Fish skin grafts with omega-3 for treatment of chronic wounds: Exploring the role of omega-3 fatty acids in wound healing and a review of clinical healing outcomes[J]. Surg Technol Int, 2022, 40: 38-46. DOI: 10.52198/22.STI.40.WH1494.

51.Kuddushi M, Shah AA, Ayranci C, et al. Recent advances in novel materials and techniques for developing transparent wound dressings[J]. J Mater Chem B, 2023, 11(27): 6201-6224. DOI: 10.1039/d3tb00639e.

52.Wang Z, Gao S, Zhang W, et al. Polyvinyl alcohol/chitosan composite hydrogels with sustained release of traditional Tibetan medicine for promoting chronic diabetic wound healing[J]. Biomater Sci, 2021, 9(10): 3821-3829. DOI: 10.1039/d1bm00346a.

53.Xiong Y, Chen L, Liu P, et al. All-in-one: multifunctional hydrogel accelerates oxidative diabetic wound healing through timed-release of exosome and fibroblast growth factor[J]. Small, 2022, 18(1): e2104229. DOI: 10.1002/smll.202104229.

54.Kwak G, Cheng J, Kim H, et al. Sustained exosome-guided macrophage polarization using hydrolytically degradable PEG hydrogels for cutaneous wound healing: identification of key proteins and MiRNAs, and sustained release formulation[J]. Small, 2022, 18(15): e2200060. DOI: 10.1002/smll.202200060.

55.Huang K, Liu W, Wei W, et al. Photothermal hydrogel encapsulating intelligently bacteria-capturing Bio-MOF for infectious wound healing[J]. ACS Nano, 2022, 16(11): 19491-19508. DOI: 10.1021/acsnano.2c09593.

56.Ngece K, Aderibigbe BA, Ndinteh DT, et al. Alginate-gum acacia based sponges as potential wound dressings for exuding and bleeding wounds[J]. Int J Biol Macromol, 2021, 172: 350-359. DOI: 10.1016/j.ijbiomac.2021.01.055.

57.Zhang M, Qian T, Deng Z, et al. 3D printed double-network alginate hydrogels containing polyphosphate for bioenergetics and bone regeneration[J]. Int J Biol Macromol, 2021, 188: 639-648. DOI: 10.1016/j.ijbiomac.2021.08.066.

58.Jiang G, Li S, Yu K, et al. A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model[J]. Acta Biomater, 2021, 128: 150-162. DOI: 10.1016/j.actbio.2021.04.010.

59.Liang X, Bai G, Niu CH, et al. High inhabitation activity of CMCS/Phytic acid/Zn2+ nanoparticles via flash nanoprecipitation (FNP) for bacterial and fungal infections[J]. Int J Biol Macromol, 2023, 242(Pt 1): 124747. DOI: 10.1016/j.ijbiomac.2023.124747.

60.Hu N, Cai Z, Jiang X, et al. Hypoxia-pretreated ADSC-derived exosome-embedded hydrogels promote angiogenesis and accelerate diabetic wound healing[J]. Acta Biomater, 2023, 157: 175-186. DOI: 10.1016/j.actbio.2022.11.057.

61.Pourtalebi Jahromi L, Rothammer M, Fuhrmann G. Polysaccharide hydrogel platforms as suitable carriers of liposomes and extracellular vesicles for dermal applications[J]. Adv Drug Deliv Rev, 2023, 200: 115028. DOI: 10.1016/j.addr.2023.115028.

62.Tsubosaka M, Kihara S, Hayashi S, et al. Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model[J]. J Orthop Res, 2020, 38(10): 2157-2169. DOI: 10.1002/jor.24688.

63.Kawahara T, Takita M, Masunaga A, et al. Fatty acid potassium had beneficial bactericidal effects and removed staphylococcus aureus biofilms while exhibiting reduced cytotoxicity towards mouse fibroblasts and human keratinocytes[J]. Int J Mol Sci, 2019, 20(2): 312. DOI: 10.3390/ijms20020312.