Skip to content
2000
Volume 22, Issue 1
  • ISSN: 1573-3998
  • E-ISSN: 1875-6417
file format text download EPUB
file format pdf download PDF
side by side viewer icon HTML

Abstract

Diabetic wounds constitute a significant global health challenge, affecting millions of individuals worldwide and imposing a substantial burden on healthcare systems. This review explores the complex pathophysiology of diabetic wound healing and discusses innovative interventions aimed at addressing this critical clinical problem. The impaired healing process in diabetic wounds is characterized by a multitude of interrelated factors, including cellular dysfunction, altered inflammatory responses, oxidative stress, the formation of advanced glycation end-products, and neurovascular abnormalities. Fibroblasts, keratinocytes, and endothelial cells demonstrate diminished proliferation and migration capabilities, while immune cells exhibit dysregulated responses, which contribute to a persistent inflammatory state. Complications associated with diabetes, such as neuropathy and vascular insufficiency, further exacerbate the wound healing process. Recent advancements in wound care strategies have opened new avenues for enhancing diabetic wound healing. These advancements encompass the development of advanced dressings and biomaterials, growth factor therapies, cell-based interventions, and gene therapy approaches. The integration of diverse treatment modalities, coupled with the management of systemic metabolic abnormalities, offers significant promise for improving outcomes in diabetic wound care. Future research should focus on optimizing combination therapies, developing personalized treatment algorithms, and conducting large-scale clinical trials to establish the most effective and safest interventions for diabetic wound healing.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cdr/10.2174/0115733998356905250706203510
2025-07-23
2026-02-21

  • From This Site

    /content/journals/cdr/10.2174/0115733998356905250706203510
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cdr/22/1/CDR-22-1-09.html?itemId=/content/journals/cdr/10.2174/0115733998356905250706203510&mimeType=html&fmt=ahah

References

  1. ArmstrongD.G. BoultonA.J.M. BusS.A. Diabetic foot ulcers and their recurrence.N. Engl. J. Med.2017376242367237510.1056/NEJMra161543928614678
     [Google Scholar]
  2. ZhangP. LuJ. JingY. TangS. ZhuD. BiY. Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis.Ann. Med.201749210611610.1080/07853890.2016.123193227585063
     [Google Scholar]
  3. SaeediP. PetersohnI. SalpeaP. MalandaB. KarurangaS. UnwinN. ColagiuriS. GuariguataL. MotalaA.A. OgurtsovaK. ShawJ.E. BrightD. WilliamsR. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.Diabetes Res. Clin. Pract.201915710784310.1016/j.diabres.2019.10784331518657
     [Google Scholar]
  4. ArmstrongD.G. TanT.W. BoultonA.J.M. BusS.A. Diabetic foot ulcers: A review.JAMA20233301627510.1001/jama.2023.1057837395769
     [Google Scholar]
  5. FalangaV. Wound healing and its impairment in the diabetic foot.Lancet200536694981736174310.1016/S0140‑6736(05)67700‑816291068
     [Google Scholar]
  6. AwasthiA. SinghS.K. KumarB. GulatiM. KumarR. WadhwaS. KhursheedR. CorrieL. KrA. KumarR. PatniP. KaurJ. VishwasS. YadavA. Treatment strategies against diabetic foot ulcer: Success so far and the road ahead.Curr. Diabetes Rev.202117442143610.2174/157339981699920110212553733143613
     [Google Scholar]
  7. OkonkwoU. DiPietroL. Diabetes and Wound Angiogenesis.Int. J. Mol. Sci.2017187141910.3390/ijms1807141928671607
     [Google Scholar]
  8. ChiuA. SharmaD. ZhaoF. Tissue engineering-based strategies for diabetic foot ulcer management.Adv. Wound Care202312314516710.1089/wound.2021.008134939837
     [Google Scholar]
  9. EverettE. MathioudakisN. Update on management of diabetic foot ulcers.Ann. N. Y. Acad. Sci.20181411115316510.1111/nyas.1356929377202
     [Google Scholar]
  10. RaghavA. KhanZ.A. LabalaR.K. AhmadJ. NoorS. MishraB.K. Financial burden of diabetic foot ulcers to world: A progressive topic to discuss always.Ther. Adv. Endocrinol. Metab.201891293110.1177/204201881774451329344337
     [Google Scholar]
  11. GurtnerG.C. WernerS. BarrandonY. LongakerM.T. Wound repair and regeneration.Nature2008453719331432110.1038/nature0703918480812
     [Google Scholar]
  12. GuoS. DiPietroL.A. Factors affecting wound healing.J. Dent. Res.201089321922910.1177/002203450935912520139336
     [Google Scholar]
  13. GosainA. DiPietroL.A. Aging and wound healing.World J. Surg.200428332132610.1007/s00268‑003‑7397‑614961191
     [Google Scholar]
  14. ClarkR.A. Fibrin and wound healing.Ann. N. Y. Acad. Sci.200193635536710.1111/j.1749‑6632.2001.tb03522.x11460492
     [Google Scholar]
  15. EmingS.A. KriegT. DavidsonJ.M. Inflammation in wound repair: Molecular and cellular mechanisms.J. Invest. Dermatol.2007127351452510.1038/sj.jid.570070117299434
     [Google Scholar]
  16. KohT.J. DiPietroL.A. Inflammation and wound healing: The role of the macrophage.Expert Rev. Mol. Med.201113e2310.1017/S146239941100194321740602
     [Google Scholar]
  17. SingerA.J. ClarkR.A.F. Cutaneous wound healing.N. Engl. J. Med.19993411073874610.1056/NEJM19990902341100610471461
     [Google Scholar]
  18. BaoP. KodraA. Tomic-CanicM. GolinkoM.S. EhrlichH.P. BremH. The role of vascular endothelial growth factor in wound healing.J. Surg. Res.2009153234735810.1016/j.jss.2008.04.02319027922
     [Google Scholar]
  19. XueM. JacksonC.J. Extracellular matrix reorganization during wound healing and its impact on abnormal scarring.Adv. Wound Care20154311913610.1089/wound.2013.048525785236
     [Google Scholar]
  20. NagaseH. VisseR. MurphyG. Structure and function of matrix metalloproteinases and TIMPs.Cardiovasc. Res.200669356257310.1016/j.cardiores.2005.12.00216405877
     [Google Scholar]
  21. BremH. Tomic-CanicM. Cellular and molecular basis of wound healing in diabetes.J. Clin. Invest.200711751219122210.1172/JCI3216917476353
     [Google Scholar]
  22. BremH. StojadinovicO. DiegelmannR.F. EnteroH. LeeB. PastarI. GolinkoM. RosenbergH. Tomic-CanicM. Molecular markers in patients with chronic wounds to guide surgical debridement.Mol. Med.2007131-2303910.2119/2006‑00054.Brem17515955
     [Google Scholar]
  23. RousselleP. MontmassonM. GarnierC. Extracellular matrix contribution to skin wound re-epithelialization.Matrix Biol.201975-76122610.1016/j.matbio.2018.01.00229330022
     [Google Scholar]
  24. RodriguesM. KosaricN. BonhamC.A. GurtnerG.C. Wound healing: A cellular perspective.Physiol. Rev.201999166570610.1152/physrev.00067.201730475656
     [Google Scholar]
  25. RodriguesM. WongV.W. RennertR.C. DavisC.R. LongakerM.T. GurtnerG.C. Progenitor cell dysfunctions underlie some diabetic complications.Am. J. Pathol.2015185102607261810.1016/j.ajpath.2015.05.00326079815
     [Google Scholar]
  26. LynchM.D. WattF.M. Fibroblast heterogeneity: Implications for human disease.J. Clin. Invest.20181281263510.1172/JCI9355529293096
     [Google Scholar]
  27. DengH. LiB. ShenQ. ZhangC. KuangL. ChenR. WangS. MaZ. LiG. Mechanisms of diabetic foot ulceration: A review.J. Diabetes202315429931210.1111/1753‑0407.1337236891783
     [Google Scholar]
  28. den DekkerA. DavisF.M. KunkelS.L. GallagherK.A. Targeting epigenetic mechanisms in diabetic wound healing.Transl. Res.2019204395010.1016/j.trsl.2018.10.00130392877
     [Google Scholar]
  29. KitaA. YamamotoS. SaitoY. ChikenjiT.S. Cellular senescence and wound healing in aged and diabetic skin.Front. Physiol.202415134411610.3389/fphys.2024.134411638440347
     [Google Scholar]
  30. WlaschekM. MaityP. MakrantonakiE. Scharffetter-KochanekK. Connective tissue and fibroblast senescence in skin aging.J. Invest. Dermatol.20211414S98599210.1016/j.jid.2020.11.01033563466
     [Google Scholar]
  31. PiipponenM. LiD. LandénN.X. The immune functions of keratinocytes in skin wound healing.Int. J. Mol. Sci.20202122879010.3390/ijms2122879033233704
     [Google Scholar]
  32. WangY. GravesD.T. Keratinocyte function in normal and diabetic wounds and modulation by FOXO1.J. Diabetes Res.202020201910.1155/2020/371470433195703
     [Google Scholar]
  33. KoK.I. SculeanA. GravesD.T. Diabetic wound healing in soft and hard oral tissues.Transl. Res.2021236728610.1016/j.trsl.2021.05.00133992825
     [Google Scholar]
  34. HuangX. LiangP. JiangB. ZhangP. YuW. DuanM. GuoL. CuiX. HuangM. HuangX. Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis.Life Sci.202025911824610.1016/j.lfs.2020.11824632791151
     [Google Scholar]
  35. YuJ.Q. LiuX.F. ChinL.K. LiuA.Q. LuoK.Q. Study of endothelial cell apoptosis using fluorescence resonance energy transfer (FRET) biosensor cell line with hemodynamic microfluidic chip system.Lab Chip201313142693270010.1039/C3LC50105A23620256
     [Google Scholar]
  36. ShawA. DohertyM.K. MutchN.J. MacRuryS.M. MegsonI.L. Endothelial cell oxidative stress in diabetes: A key driver of cardiovascular complications?Biochem. Soc. Trans.201442492893310.1042/BST2014011325109981
     [Google Scholar]
  37. DognéS. FlamionB. Endothelial glycocalyx impairment in disease.Am. J. Pathol.2020190476878010.1016/j.ajpath.2019.11.01632035885
     [Google Scholar]
  38. KolluruG.K. BirS.C. KevilC.G. Endothelial dysfunction and diabetes: Effects on angiogenesis, vascular remodeling, and wound healing.Int. J. Vasc. Med.2012201213010.1155/2012/91826722611498
     [Google Scholar]
  39. YangS. WangS. ChenL. WangZ. ChenJ. NiQ. GuoX. ZhangL. XueG. Neutrophil extracellular traps delay diabetic wound healing by inducing endothelial-to-mesenchymal transition via the hippo pathway.Int. J. Biol. Sci.202319134736110.7150/ijbs.7804636594092
     [Google Scholar]
  40. ZhaoR. LiangH. ClarkeE. JacksonC. XueM. Inflammation in Chronic Wounds.Int. J. Mol. Sci.20161712208510.3390/ijms1712208527973441
     [Google Scholar]
  41. WongS.L. DemersM. MartinodK. GallantM. WangY. GoldfineA.B. KahnC.R. WagnerD.D. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing.Nat. Med.201521781581910.1038/nm.388726076037
     [Google Scholar]
  42. LiuD. YangP. GaoM. YuT. ShiY. ZhangM. YaoM. LiuY. ZhangX. NLRP3 activation induced by neutrophil extracellular traps sustains inflammatory response in the diabetic wound.Clin. Sci.2019133456558210.1042/CS2018060030626731
     [Google Scholar]
  43. Al SadounH. Macrophage phenotypes in normal and diabetic wound healing and therapeutic interventions.Cells202211151110.3390/cells1115243035954275
     [Google Scholar]
  44. KimballA. SchallerM. JoshiA. DavisF.M. denDekkerA. BoniakowskiA. BermickJ. ObiA. MooreB. HenkeP.K. KunkelS.L. GallagherK.A. Ly6CHi blood monocyte/macrophage drive chronic inflammation and impair wound healing in diabetes mellitus.Arterioscler. Thromb. Vasc. Biol.20183851102111410.1161/ATVBAHA.118.31070329496661
     [Google Scholar]
  45. LouiselleA.E. NiemiecS.M. ZgheibC. LiechtyK.W. Macrophage polarization and diabetic wound healing.Transl. Res.202123610911610.1016/j.trsl.2021.05.00634089902
     [Google Scholar]
  46. BoniakowskiA.E. KimballA.S. JacobsB.N. KunkelS.L. GallagherK.A. Macrophage-mediated inflammation in normal and diabetic wound healing.J. Immunol.20171991172410.4049/jimmunol.170022328630109
     [Google Scholar]
  47. LiM. HouQ. ZhongL. ZhaoY. FuX. Macrophage related chronic inflammation in non-healing wounds.Front. Immunol.20211268171010.3389/fimmu.2021.68171034220830
     [Google Scholar]
  48. MirzaR.E. FangM.M. Weinheimer-HausE.M. EnnisW.J. KohT.J. Sustained inflammasome activity in macrophages impairs wound healing in type 2 diabetic humans and mice.Diabetes20146331103111410.2337/db13‑092724194505
     [Google Scholar]
  49. LvD. CaoX. ZhongL. DongY. XuZ. RongY. XuH. WangZ. YangH. YinR. ChenM. KeC. HuZ. DengW. TangB. Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing.Cell Rep. Med.20234810112910.1016/j.xcrm.2023.10112937480849
     [Google Scholar]
  50. MaruyamaK. AsaiJ. IiM. ThorneT. LosordoD.W. D’AmoreP.A. Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing.Am. J. Pathol.200717041178119110.2353/ajpath.2007.06001817392158
     [Google Scholar]
  51. AitchesonS.M. FrentiuF.D. HurnS.E. EdwardsK. MurrayR.Z. Skin wound healing: Normal macrophage function and macrophage dysfunction in diabetic wounds.Molecules202126162610.3390/molecules2616491734443506
     [Google Scholar]
  52. SharifiaghdamM. ShaabaniE. Faridi-MajidiR. De SmedtS.C. BraeckmansK. FraireJ.C. Macrophages as a therapeutic target to promote diabetic wound healing.Mol. Ther.20223092891290810.1016/j.ymthe.2022.07.01635918892
     [Google Scholar]
  53. RoderoM.P. KhosrotehraniK. Skin wound healing modulation by macrophages.Int. J. Clin. Exp. Pathol.20103764365320830235
     [Google Scholar]
  54. MirzaR. KohT.J. Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice.Cytokine201156225626410.1016/j.cyto.2011.06.01621803601
     [Google Scholar]
  55. MiaoM. NiuY. XieT. YuanB. QingC. LuS. Diabetes-impaired wound healing and altered macrophage activation: A possible pathophysiologic correlation.Wound Repair Regen.201220220321310.1111/j.1524‑475X.2012.00772.x22380690
     [Google Scholar]
  56. BarrosJ.F. WaclawiakI. PecliC. BorgesP.A. GeorgiiJ.L. Ramos-JuniorE.S. CanettiC. CourauT. KlatzmannD. KunkelS.L. PenidoC. CantoF.B. BenjamimC.F. Role of Chemokine Receptor CCR4 and Regulatory T Cells in Wound Healing of Diabetic Mice.J. Invest. Dermatol.201913951161117010.1016/j.jid.2018.10.03930465800
     [Google Scholar]
  57. AuduC.O. WolfS.J. JoshiA.D. MoonJ.Y. MelvinW.J. SharmaS.B. DavisF.M. ObiA.T. WasikowskiR. TsoiL.C. BarrettE.C. MangumK.D. BauerT.M. KunkelS.L. MooreB.B. GallagherK.A. Histone demethylase JARID1C/KDM5C regulates Th17 cells by increasing IL-6 expression in diabetic plasmacytoid dendritic cells.JCI Insight2024912e17295910.1172/jci.insight.17295938912581
     [Google Scholar]
  58. XuP. FuX. XiaoN. GuoY. PeiQ. PengY. ZhangY. YaoM. Involvements of γδT Lymphocytes in Acute and Chronic Skin Wound Repair.Inflammation20174041416142710.1007/s10753‑017‑0585‑628540539
     [Google Scholar]
  59. LiuZ. XuY. ChenL. XieJ. TangJ. ZhaoJ. ShuB. QiS. ChenJ. LiangG. LuoG. WuJ. HeW. LiuX. Dendritic epidermal T cells facilitate wound healing in diabetic mice.Am. J. Transl. Res.2016852375238427347345
     [Google Scholar]
  60. NishikoriY. ShiotaN. OkunishiH. The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice.Arch. Dermatol. Res.2014306982383510.1007/s00403‑014‑1496‑025218083
     [Google Scholar]
  61. DongJ. ChenL. ZhangY. JayaswalN. MezghaniI. ZhangW. VevesA. Mast cells in diabetes and diabetic wound healing.Adv. Ther.202037114519453710.1007/s12325‑020‑01499‑432935286
     [Google Scholar]
  62. TellecheaA. LealE.C. KafanasA. AusterM.E. KuchibhotlaS. OstrovskyY. TecilazichF. BaltzisD. ZhengY. CarvalhoE. ZabolotnyJ.M. WengZ. PetraA. PatelA. PanagiotidouS. Pradhan-NabzdykL. TheoharidesT.C. VevesA. Mast cells regulate wound healing in diabetes.Diabetes20166572006201910.2337/db15‑034027207516
     [Google Scholar]
  63. TheocharidisG. BaltzisD. RoustitM. TellecheaA. DangwalS. KhetaniR.S. ShuB. ZhaoW. FuJ. BhasinS. KafanasA. HuiD. SuiS.H. PatsopoulosN.A. BhasinM. VevesA. Integrated skin transcriptomics and serum multiplex assays reveal novel mechanisms of wound healing in diabetic foot ulcers.Diabetes202069102157216910.2337/db20‑018832763913
     [Google Scholar]
  64. NieminenJ.K. VakkilaJ. SaloH.M. EkströmN. HärkönenT. IlonenJ. KnipM. VaaralaO. Altered phenotype of peripheral blood dendritic cells in pediatric type 1 diabetes.Diabetes Care201235112303231010.2337/dc11‑246022787171
     [Google Scholar]
  65. KhannaS. BiswasS. ShangY. CollardE. AzadA. KauhC. BhaskerV. GordilloG.M. SenC.K. RoyS. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice.PLoS One201053e953910.1371/journal.pone.000953920209061
     [Google Scholar]
  66. WillenborgS. LucasT. van LooG. KnipperJ.A. KriegT. HaaseI. BrachvogelB. HammerschmidtM. NagyA. FerraraN. PasparakisM. EmingS.A. CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair.Blood2012120361362510.1182/blood‑2012‑01‑40338622577176
     [Google Scholar]
  67. ChengP. XieX. HuL. ZhouW. MiB. XiongY. XueH. ZhangK. ZhangY. HuY. ChenL. ZhaK. LvB. LinZ. LinC. DaiG. HuY. YuT. HuH. LiuG. ZhangY. Hypoxia endothelial cells-derived exosomes facilitate diabetic wound healing through improving endothelial cell function and promoting M2 macrophages polarization.Bioact. Mater.20243315717310.1016/j.bioactmat.2023.10.02038034500
     [Google Scholar]
  68. LiS. DingX. ZhangH. DingY. TanQ. IL-25 improves diabetic wound healing through stimulating M2 macrophage polarization and fibroblast activation.Int. Immunopharmacol.202210610860510.1016/j.intimp.2022.10860535149293
     [Google Scholar]
  69. OkizakiS. ItoY. HosonoK. ObaK. OhkuboH. AmanoH. ShichiriM. MajimaM. Suppressed recruitment of alternatively activated macrophages reduces TGF-β1 and impairs wound healing in streptozotocin-induced diabetic mice.Biomed. Pharmacother.20157031732510.1016/j.biopha.2014.10.02025677561
     [Google Scholar]
  70. WoodS. JayaramanV. HuelsmannE.J. BonishB. BurgadD. SivaramakrishnanG. QinS. DiPietroL.A. ZlozaA. ZhangC. ShafikhaniS.H. Pro-inflammatory chemokine CCL2 (MCP-1) promotes healing in diabetic wounds by restoring the macrophage response.PLoS One201493e9157410.1371/journal.pone.009157424618995
     [Google Scholar]
  71. ChuZ. HuangQ. MaK. LiuX. ZhangW. CuiS. WeiQ. GaoH. HuW. WangZ. MengS. TianL. LiH. FuX. ZhangC. Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles.Bioact. Mater.20232725727010.1016/j.bioactmat.2023.04.00737122894
     [Google Scholar]
  72. ZhuS. YuY. RenY. XuL. WangH. LingX. JinL. HuY. ZhangH. MiaoC. GuoK. The emerging roles of neutrophil extracellular traps in wound healing.Cell Death Dis.2021121198410.1038/s41419‑021‑04294‑334686654
     [Google Scholar]
  73. DengL. DuC. SongP. ChenT. RuiS. ArmstrongD.G. DengW. The role of oxidative stress and antioxidants in diabetic wound healing.Oxid. Med. Cell. Longev.20212021885275910.1155/2021/885275933628388
     [Google Scholar]
  74. LuoJ.D. WangY.Y. FuW.L. WuJ. ChenA.F. Gene therapy of endothelial nitric oxide synthase and manganese superoxide dismutase restores delayed wound healing in type 1 diabetic mice.Circulation2004110162484249310.1161/01.CIR.0000137969.87365.0515262829
     [Google Scholar]
  75. ZhangW. ChenL. XiongY. PanayiA.C. AbududilibaierA. HuY. YuC. ZhouW. SunY. LiuM. XueH. HuL. YanC. XieX. LinZ. CaoF. MiB. LiuG. Antioxidant therapy and antioxidant-related bionanomaterials in diabetic wound healing.Front. Bioeng. Biotechnol.2021970747910.3389/fbioe.2021.70747934249895
     [Google Scholar]
  76. VolpeC.M.O. Villar-DelfinoP.H. Dos AnjosP.M.F. Nogueira-MachadoJ.A. Cellular death, reactive oxygen species (ROS) and diabetic complications.Cell Death Dis.20189211910.1038/s41419‑017‑0135‑z29371661
     [Google Scholar]
  77. GiaccoF. BrownleeM. Oxidative stress and diabetic complications.Circ. Res.201010791058107010.1161/CIRCRESAHA.110.22354521030723
     [Google Scholar]
  78. GoldinA. BeckmanJ.A. SchmidtA.M. CreagerM.A. Advanced glycation end products: Sparking the development of diabetic vascular injury.Circulation2006114659760510.1161/CIRCULATIONAHA.106.62185416894049
     [Google Scholar]
  79. DuraisamyY. SlevinM. SmithN. BaileyJ. ZweitJ. SmithC. AhmedN. GaffneyJ. Effect of glycation on basic fibroblast growth factor induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: Possible relevance to wound healing in diabetes.Angiogenesis20014427728810.1023/A:101606891726612197473
     [Google Scholar]
  80. GuoY. LinC. XuP. WuS. FuX. XiaW. YaoM. AGEs induced autophagy impairs cutaneous wound healing via stimulating macrophage polarization to M1 in diabetes.Sci. Rep.2016613641610.1038/srep3641627805071
     [Google Scholar]
  81. Volmer-TholeM. LobmannR. Neuropathy and diabetic foot syndrome.Int. J. Mol. Sci.201617691710.3390/ijms1706091727294922
     [Google Scholar]
  82. HicksC.W. SelvinE. Epidemiology of peripheral neuropathy and lower extremity disease in diabetes.Curr. Diab. Rep.201919108610.1007/s11892‑019‑1212‑831456118
     [Google Scholar]
  83. LiuY. SebastianB. LiuB. ZhangY. FisselJ.A. PanB. PolydefkisM. FarahM.H. Sensory and autonomic function and structure in footpads of a diabetic mouse model.Sci. Rep.2017714140110.1038/srep4140128128284
     [Google Scholar]
  84. McDermottK. FangM. BoultonA.J.M. SelvinE. HicksC.W. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers.Diabetes Care202346120922110.2337/dci22‑004336548709
     [Google Scholar]
  85. LimJ.Z.M. NgN.S.L. ThomasC. Prevention and treatment of diabetic foot ulcers.J. R. Soc. Med.2017110310410910.1177/014107681668834628116957
     [Google Scholar]
  86. MarrotteE.J. ChenD.D. HakimJ.S. ChenA.F. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice.J. Clin. Invest.2010120124207421910.1172/JCI3685821060152
     [Google Scholar]
  87. TepperO.M. GalianoR.D. CaplaJ.M. KalkaC. GagneP.J. JacobowitzG.R. LevineJ.P. GurtnerG.C. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures.Circulation2002106222781278610.1161/01.CIR.0000039526.42991.9312451003
     [Google Scholar]
  88. ChenY. LiY. YangX. CaoZ. NieH. BianY. YangG. Glucose-triggered in situ forming keratin hydrogel for the treatment of diabetic wounds.Acta Biomater.202112520821810.1016/j.actbio.2021.02.03533662598
     [Google Scholar]
  89. CampitielloF. ManconeM. Della CorteA. GuernieroR. CanonicoS. To evaluate the efficacy of an acellular Flowable matrix in comparison with a wet dressing for the treatment of patients with diabetic foot ulcers: A randomized clinical trial.Updates Surg.201769452352910.1007/s13304‑017‑0461‑928497218
     [Google Scholar]
  90. KordestaniS. ShahrezaeeM. TahmasebiM.N. HajimahmodiH. GhasemaliD.H. AbyanehM.S. A randomised controlled trial on the effectiveness of an advanced wound dressing used in Iran.J. Wound Care200817732332710.12968/jowc.2008.17.7.3052518705234
     [Google Scholar]
  91. YangJ. ZengW. XuP. FuX. YuX. ChenL. LengF. YuC. YangZ. Glucose-responsive multifunctional metal–organic drug-loaded hydrogel for diabetic wound healing.Acta Biomater.202214020621810.1016/j.actbio.2021.11.04334879294
     [Google Scholar]
  92. WangW. LuK. YuC. HuangQ. DuY.Z. Nano-drug delivery systems in wound treatment and skin regeneration.J. Nanobiotechnology20191718210.1186/s12951‑019‑0514‑y31291960
     [Google Scholar]
  93. KumarM. HillesA.R. GeY. BhatiaA. MahmoodS. A review on polysaccharides mediated electrospun nanofibers for diabetic wound healing: Their current status with regulatory perspective.Int. J. Biol. Macromol.202323412369610.1016/j.ijbiomac.2023.12369636801273
     [Google Scholar]
  94. AugustineR. ZahidA.A. HasanA. WangM. WebsterT.J. CTGF loaded electrospun dual porous core-shell membrane for diabetic wound healing.Int. J. Nanomedicine2019148573858810.2147/IJN.S22404731802870
     [Google Scholar]
  95. LouP. LiuS. WangY. PanC. XuX. ZhaoM. LiaoG. YangG. YuanY. LiL. ZhangJ. ChenY. ChengJ. LuY. LiuJ. Injectable self-assembling peptide nanofiber hydrogel as a bioactive 3D platform to promote chronic wound tissue regeneration.Acta Biomater.202113510011210.1016/j.actbio.2021.08.00834389483
     [Google Scholar]
  96. ZhaoP. ZhouG. JiangJ. LiH. XiangX. Platelet-rich Plasma (PRP) in the treatment of diabetic foot ulcers and its regulation of autophagy.Int. J. Low. Extrem. Wounds20231534734622114493710.1177/1534734622114493736652558
     [Google Scholar]
  97. OuYangH. TangY. YangF. RenX. YangJ. CaoH. YinY. Platelet-rich plasma for the treatment of diabetic foot ulcer: A systematic review.Front. Endocrinol.202314125608110.3389/fendo.2023.125608138169990
     [Google Scholar]
  98. BennettS.P. GriffithsG.D. SchorA.M. LeeseG.P. SchorS.L. Growth factors in the treatment of diabetic foot ulcers.Br. J. Surg.200390213314610.1002/bjs.401912555288
     [Google Scholar]
  99. SteedD.L. GoslenJ.B. HollowayG.A. MaloneJ.M. BuntT.J. WebsterM.W. Randomized prospective double-blind trial in healing chronic diabetic foot ulcers. CT-102 activated platelet supernatant, topical versus placebo.Diabetes Care199215111598160410.2337/diacare.15.11.15981468291
     [Google Scholar]
  100. DixonD. EdmondsM. Managing diabetic foot ulcers: Pharmacotherapy for wound healing.Drugs2021811295610.1007/s40265‑020‑01415‑833382445
     [Google Scholar]
  101. AckermannM. WolloscheckT. WellmannA. LiV.W. LiW.W. KonerdingM.A. Priming with a combination of proangiogenic growth factors enhances wound healing in streptozotocin-induced diabetes in mice.Eur. Surg. Res.2011472818910.1159/00032814321720165
     [Google Scholar]
  102. DekoninckS. BlanpainC. Stem cell dynamics, migration and plasticity during wound healing.Nat. Cell Biol.2019211182410.1038/s41556‑018‑0237‑630602767
     [Google Scholar]
  103. OjehN. PastarI. Tomic-CanicM. StojadinovicO. Stem cells in skin regeneration, wound healing, and their clinical applications.Int. J. Mol. Sci.20151610254762550110.3390/ijms16102547626512657
     [Google Scholar]
  104. XueZ. LiaoY. LiY. Effects of microenvironment and biological behavior on the paracrine function of stem cells.Genes Dis.202411113514710.1016/j.gendis.2023.03.01337588208
     [Google Scholar]
  105. Guillamat-PratsR. The role of MSC in wound healing, scarring and regeneration.Cells20211071010.3390/cells1007172934359898
     [Google Scholar]
  106. YangR. LiuF. WangJ. ChenX. XieJ. XiongK. Epidermal stem cells in wound healing and their clinical applications.Stem Cell Res. Ther.201910122910.1186/s13287‑019‑1312‑z31358069
     [Google Scholar]
  107. ZhangY. ZhangY.Y. PanZ.W. LiQ.Q. SunL.H. LiX. GongM.Y. GDF11 promotes wound healing in diabetic mice via stimulating HIF-1a-VEGF/SDF-1a-mediated endothelial progenitor cell mobilization and neovascularization.Acta Pharmacol. Sin.202344999101310.1038/s41401‑022‑01013‑236347996
     [Google Scholar]
  108. Ruiz-SalmeronR. De La Cuesta-DiazA. Constantino-BermejoM. Pérez-CamachoI. Marcos-SánchezF. HmadchaA. SoriaB. Angiographic demonstration of neoangiogenesis after intra-arterial infusion of autologous bone marrow mononuclear cells in diabetic patients with critical limb ischemia.Cell Transplant.201120101629163910.3727/096368910X017722289660
     [Google Scholar]
  109. Arango-RodríguezM.L. Solarte-DavidV.A. Becerra-BayonaS.M. CallegariE. PaezM.D. SossaC.L. VeraM.E.O. MateusL.C. Eduardo serranoS. Ardila-RoaA.K. ViviescasL.T.G. Role of mesenchymal stromal cells derivatives in diabetic foot ulcers: A controlled randomized phase 1/2 clinical trial.Cytotherapy202224101035104810.1016/j.jcyt.2022.04.00236084965
     [Google Scholar]
  110. DashN.R. DashS.N. RoutrayP. MohapatraS. MohapatraP.C. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells.Rejuvenation Res.200912535936610.1089/rej.2009.087219929258
     [Google Scholar]
  111. LaivaA.L. O’BrienF.J. KeoghM.B. Innovations in gene and growth factor delivery systems for diabetic wound healing.J. Tissue Eng. Regen. Med.2018121e296e31210.1002/term.244328482114
     [Google Scholar]
  112. JinW. ChenX. KongL. HuangC. Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing.Front. Immunol.20221396092510.3389/fimmu.2022.96092535990676
     [Google Scholar]
  113. BlumeP. DriverV.R. TallisA.J. KirsnerR.S. KroekerR. PayneW.G. WaliS. MarstonW. DoveC. EnglerR.L. ChandlerL.A. SosnowskiB.K. Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers.Wound Repair Regen.201119330230810.1111/j.1524‑475X.2011.00669.x21371164
     [Google Scholar]
  114. HennD. ZhaoD. SivarajD. TrotsyukA. BonhamC.A. FischerK.S. KehlT. FehlmannT. GrecoA.H. KussieH.C. Moortgat IllouzS.E. PadmanabhanJ. BarreraJ.A. KneserU. LenhofH.P. JanuszykM. LeviB. KellerA. LongakerM.T. ChenK. QiL.S. GurtnerG.C. Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing.Nat. Commun.2023141472910.1038/s41467‑023‑40519‑z37550295
     [Google Scholar]
  115. IcliB. NabzdykC.S. Lujan-HernandezJ. CahillM. AusterM.E. WaraA.K.M. SunX. OzdemirD. GiatsidisG. OrgillD.P. FeinbergM.W. Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a.J. Mol. Cell. Cardiol.20169115115910.1016/j.yjmcc.2016.01.00726776318
     [Google Scholar]
  116. YanC. ChenJ. WangC. YuanM. KangY. WuZ. LiW. ZhangG. MachensH.G. RinkevichY. ChenZ. YangX. XuX. Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis.Drug Deliv.202229121422810.1080/10717544.2021.202369934985397
     [Google Scholar]
  117. IcliB. WaraA.K.M. MoslehiJ. SunX. PlovieE. CahillM. MarchiniJ.F. SchisslerA. PaderaR.F. ShiJ. ChengH.W. RaghuramS. AranyZ. LiaoR. CroceK. MacRaeC. FeinbergM.W. MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling.Circ. Res.2013113111231124110.1161/CIRCRESAHA.113.30178024047927
     [Google Scholar]
  118. XuJ. WuW. ZhangL. Dorset-MartinW. MorrisM.W. MitchellM.E. LiechtyK.W. The role of microRNA-146a in the pathogenesis of the diabetic wound-healing impairment: Correction with mesenchymal stem cell treatment.Diabetes201261112906291210.2337/db12‑014522851573
     [Google Scholar]
  119. YeJ. KangY. SunX. NiP. WuM. LuS. MicroRNA-155 inhibition promoted wound healing in diabetic rats.Int. J. Low. Extrem. Wounds2017162748410.1177/153473461770663628682732
     [Google Scholar]
  120. MouraJ. SørensenA. LealE.C. SvendsenR. CarvalhoL. WillemoesR.J. JørgensenP.T. JenssenH. WengelJ. DalgaardL.T. CarvalhoE. microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation.Sci. Rep.201991583610.1038/s41598‑019‑42309‑430967591
     [Google Scholar]
  121. CaskeyR.C. ZgheibC. MorrisM. AllukianM. Dorsett-MartinW. XuJ. WuW. LiechtyK.W. Dysregulation of collagen production in diabetes following recurrent skin injury: Contribution to the development of a chronic wound.Wound Repair Regen.201422451552010.1111/wrr.1219924898050
     [Google Scholar]
  122. LiB. ZhouY. ChenJ. WangT. LiZ. FuY. ZhaiA. BiC. Long noncoding RNA H19 acts as a miR-29b sponge to promote wound healing in diabetic foot ulcer.FASEB J.2021351e2052610.1096/fj.201900076RRRRR33174326
     [Google Scholar]
  123. XuJ. ZgheibC. HodgesM.M. CaskeyR.C. HuJ. LiechtyK.W. Mesenchymal stem cells correct impaired diabetic wound healing by decreasing ECM proteolysis.Physiol. Genomics2017491054154810.1152/physiolgenomics.00090.201628842435
     [Google Scholar]
  124. FasanaroP. D’AlessandraY. Di StefanoV. MelchionnaR. RomaniS. PompilioG. CapogrossiM.C. MartelliF. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3.J. Biol. Chem.200828323158781588310.1074/jbc.M80073120018417479
     [Google Scholar]
  125. HuS. HuangM. LiZ. JiaF. GhoshZ. LijkwanM.A. FasanaroP. SunN. WangX. MartelliF. RobbinsR.C. WuJ.C. MicroRNA-210 as a novel therapy for treatment of ischemic heart disease.Circulation201012211 SupplS124S13110.1161/CIRCULATIONAHA.109.92842420837903
     [Google Scholar]
  126. SumpioB.J. DallasA. BergerA.G. LiZ. WangE. MezghaniI. ContrerasM. TheocharidisG. IlvesH. HammondP.T. JohnstonB.H. VevesA. Use of therapeutic RNAs to accelerate wound healing in diabetic rabbit wounds.Adv. Wound Care202413943544510.1089/wound.2023.005638183631
     [Google Scholar]
  127. ChanY.C. RoyS. KhannaS. SenC.K. Downregulation of endothelial microRNA-200b supports cutaneous wound angiogenesis by desilencing GATA binding protein 2 and vascular endothelial growth factor receptor 2.Arterioscler. Thromb. Vasc. Biol.20123261372138210.1161/ATVBAHA.112.24858322499991
     [Google Scholar]
  128. AnF. GongB. WangH. YuD. ZhaoG. LinL. TangW. YuH. BaoS. XieQ. miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure.Apoptosis201217770271610.1007/s10495‑012‑0704‑722374434
     [Google Scholar]
  129. XuJ. ZgheibC. HuJ. WuW. ZhangL. LiechtyK.W. The role of microRNA-15b in the impaired angiogenesis in diabetic wounds.Wound Repair Regen.201422567167710.1111/wrr.1221725059098
     [Google Scholar]
  130. LiX. LiD. WangA. ChuT. LohcharoenkalW. ZhengX. GrünlerJ. NarayananS. EliassonS. HerterE.K. WangY. MaY. EhrströmM. EidsmoL. KasperM. PivarcsiA. SonkolyE. CatrinaS.B. StåhleM. Xu LandénN. MicroRNA-132 with therapeutic potential in chronic wounds.J. Invest. Dermatol.2017137122630263810.1016/j.jid.2017.08.00328807666
     [Google Scholar]
  131. RossK. MiR equal than others: MicroRNA enhancement for cutaneous wound healing.J. Cell. Physiol.2021236128050805910.1002/jcp.3048534160067
     [Google Scholar]
  132. SarthiS. BhardwajH. Kumar JangdeR. Advances in nucleic acid delivery strategies for diabetic wound therapy.J. Clin. Transl. Endocrinol.20243710036610.1016/j.jcte.2024.10036639286540
     [Google Scholar]
  133. HuiQ. ZhangL. YangX. YuB. HuangZ. PangS. ZhouQ. YangR. LiW. HuL. LiX. CaoG. WangX. Higher biostability of rh-aFGF-Carbomer 940 hydrogel and its effect on wound healing in a diabetic rat model.ACS Biomater. Sci. Eng.2018451661810.1021/acsbiomaterials.8b0001133445322
     [Google Scholar]
  134. RafteryR.M. Mencía CastañoI. ChenG. CavanaghB. QuinnB. CurtinC.M. CryanS.A. O’BrienF.J. Translating the role of osteogenic-angiogenic coupling in bone formation: Highly efficient chitosan-pDNA activated scaffolds can accelerate bone regeneration in critical-sized bone defects.Biomaterials201714911612710.1016/j.biomaterials.2017.09.03629024837
     [Google Scholar]
  135. WitschE. SelaM. YardenY. Roles for growth factors in cancer progression.Physiology20102528510110.1152/physiol.00045.200920430953
     [Google Scholar]
  136. ShafieeS. HeidarpourM. SabbaghS. AminiE. SaffariH. DolatiS. MeamarR. Stem cell transplantation therapy for diabetic foot ulcer: A narrative review.Asian Biomed.202115131810.2478/abm‑2021‑000237551298
     [Google Scholar]
  137. KustikovaO. BrugmanM. BaumC. The genomic risk of somatic gene therapy.Semin. Cancer Biol.201020426927810.1016/j.semcancer.2010.06.00320600920
     [Google Scholar]
/content/journals/cdr/10.2174/0115733998356905250706203510
Loading
Mechanisms and Interventions of Diabetic Wound Healing
Curr. Diabetes Rev. 22, E15733998356905 (2026); https://doi.org/10.2174/0115733998356905250706203510
/content/journals/cdr/10.2174/0115733998356905250706203510
/content/journals/cdr/10.2174/0115733998356905250706203510
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): altered inflammatory responses; cellular dysfunction; Diabetic wound healing; diabetic wounds; glycation end-products; oxidative stress

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test