Immune cells in diabetic wound repair: the key to better wound management

Abstract

Chronic diabetic ulcers (DUs) pose a significant clinical challenge with high amputation and mortality rates, impacting over 131 million people worldwide and incurring approximately $755 billion in annual healthcare costs. Immune cells play indispensable roles in orchestrating wound healing; however, existing reviews often overlook the temporal heterogeneity of immune cell subsets in DUs. To bridge this gap, this review comprehensively examines the roles and characteristics of immune cells in DUs healing, involving monocytes, macrophages, dendritic cells, neutrophils, mast cells, B cells, T cells, and natural killer cells, with a focus on their distribution and dysregulation throughout different stages of wound healing. Furthermore, we highlight advances in immune cell-targeted modulation and the emerging therapeutic promise of topical anti-cytokine biologics in diabetic wound care. We uniquely emphasize the dynamic transitions of monocyte subsets and offer a systematic evaluation of the controversial roles of macrophage M1/M2 polarization. This review underscores emerging therapeutic strategies that leverage immune cell modulation, offering insights into more effective DU management.

Keywords

diabetic ulcers / macrophages / neutrophils / wound healing / targeted therapies

References

[1] Zhang Y , Lazzarini PA , McPhail SM , van Netten JJ , Armstrong DG , Pacella RE . Global disability burdens of diabetes-related lower-extremity complications in 1990 and 2016. Diabetes Care 2020; 43(5): 964–974

[2] Graves N , Phillips CJ , Harding K . A narrative review of the epidemiology and economics of chronic wounds. Br J Dermatol 2022; 187(2): 141–148

[3] Armstrong DG , Swerdlow MA , Armstrong AA , Conte MS , Padula WV , Bus SA . Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer. J Foot Ankle Res 2020; 13(1): 16

[4] Driver VR , Fabbi M , Lavery LA , Gibbons G . The costs of diabetic foot: the economic case for the limb salvage team. J Vasc Surg 2010; 52(3 Suppl): 17S–22S

[5] Lu Q , Wang J , Wei X , Wang G , Xu Y , Lu Z , Liu P . Cost of diabetic foot ulcer management in China: a 7-year single-center retrospective review. Diabetes Metab Syndr Obes 2020; 13: 4249–4260

[6] Jiang Y , Wang X , Xia L , Fu X , Xu Z , Ran X , Yan L , Li Q , Mo Z , Yan Z , Ji Q , Li Q . A cohort study of diabetic patients and diabetic foot ulceration patients in China. Wound Repair Regen 2015; 23(2): 222–230

[7] Peña OA , Martin P . Cellular and molecular mechanisms of skin wound healing. Nat Rev Mol Cell Biol 2024; 25(8): 599–616

[8] Zeng R , Lv B , Lin Z , Chu X , Xiong Y , Knoedler S , Cao F , Lin C , Chen L , Yu C , Liao J , Zhou W , Dai G , Shahbazi MA , Mi B , Liu G . Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds. Bioact Mater 2024; 34: 366–380

[9] Brinkmann V , Reichard U , Goosmann C , Fauler B , Uhlemann Y , Weiss DS , Weinrauch Y , Zychlinsky A . Neutrophil extracellular traps kill bacteria. Science 2004; 303(5663): 1532–1535

[10] Eming SA , Krieg T , Davidson JM . Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 2007; 127(3): 514–525

[11] Barrientos S , Stojadinovic O , Golinko MS , Brem H , Tomic-Canic M . Growth factors and cytokines in wound healing. Wound Repair Regen 2008; 16(5): 585–601

[12] Du Cheyne C , Tay H , De Spiegelaere W . The complex TIE between macrophages and angiogenesis. Anat Histol Embryol 2020; 49(5): 585–596

[13] Sharifiaghdam M , Shaabani E , Faridi-Majidi R , De Smedt SC , Braeckmans K , Fraire JC . Macrophages as a therapeutic target to promote diabetic wound healing. Mol Ther 2022; 30(9): 2891–2908

[14] Mahdavian Delavary B , van der Veer WM , van Egmond M , Niessen FB , Beelen RH . Macrophages in skin injury and repair. Immunobiology 2011; 216(7): 753–762

[15] Nosbaum A , Prevel N , Truong HA , Mehta P , Ettinger M , Scharschmidt TC , Ali NH , Pauli ML , Abbas AK , Rosenblum MD . Cutting edge: regulatory T cells facilitate cutaneous wound healing. J Immunol 2016; 196(5): 2010–2014

[16] Weller K , Foitzik K , Paus R , Syska W , Maurer M , Weller K , Foitzik K , Paus R , Syska W , Maurer M . Mast cells are required for normal healing of skin wounds in mice. FASEB J 2006; 20(13): 2366–2368

[17] Gurish MF , Austen KF . Developmental origin and functional specialization of mast cell subsets. Immunity 2012; 37(1): 25–33

[18] Dong J , Chen L , Zhang Y , Jayaswal N , Mezghani I , Zhang W , Veves A . Mast cells in diabetes and diabetic wound healing. Adv Ther 2020; 37(11): 4519–4537

[19] Komi DEA , Khomtchouk K , Santa Maria PL . A review of the contribution of mast cells in wound healing: involved molecular and cellular mechanisms. Clin Rev Allergy Immunol 2020; 58(3): 298–312

[20] Maurer M , Opitz M , Henz BM , Paus R . The mast cell products histamine and serotonin stimulate and TNF-alpha inhibits the proliferation of murine epidermal keratinocytes in situ. J Dermatol Sci 1997; 16(1): 79–84

[21] Levi-Schaffer F , Kupietzky A . Mast cells enhance migration and proliferation of fibroblasts into an in vitro wound. Exp Cell Res 1990; 188(1): 42–49

[22] Theocharidis G , Baltzis D , Roustit M , Tellechea A , Dangwal S , Khetani RS , Shu B , Zhao W , Fu J , Bhasin S , Kafanas A , Hui D , Sui SH , Patsopoulos NA , Bhasin M , Veves A . Integrated skin transcriptomics and serum multiplex assays reveal novel mechanisms of wound healing in diabetic foot ulcers. Diabetes 2020; 69(10): 2157–2169

[23] Tellechea A , Lea EC , Kafanas A , Auster ME , Kuchibhotla S , Ostrovsky Y , Tecilazich F , Baltzis D , Zheng Y , Carvalho E , Zabolotny JM , Weng Z , Petra A , Patel A , Panagiotidou S , Pradhan-Nabzdyk L , Theoharides TC , Veves A . Mast cells regulate wound healing in diabetes. Diabetes 2016; 65(7): 2006–2019

[24] McLaughlin PJ , Immonen JA , Zagon IS . Topical naltrexone accelerates full-thickness wound closure in type 1 diabetic rats by stimulating angiogenesis. Exp Biol Med (Maywood) 2013; 238(7): 733–743

[25] Babaei S , Bayat M . Effect of pentoxifylline administration on mast cell numbers and degranulation in a diabetic and normoglycemic rat model wound healing. Iran Red Crescent Med J 2012; 14(8): 483–487

[26] Soleimani H , Amini A , Abdollahifar MA , Norouzian M , Kouhkheil R , Mostafavinia A , Ghoreishi SK , Bayat S , Chien S , Bayat M . Combined effects of photobiomodulation and curcumin on mast cells and wound strength in wound healing of streptozotocin-induced diabetes in rats. Lasers Med Sci 2021; 36(2): 375–386

[27] Özay Y , Güzel S , Yumrutaş Ö , Pehlivanoğlu B , Erdoğdu İH , Yildirim Z , Türk BA , Darcan S . Wound healing effect of kaempferol in diabetic and nondiabetic rats. J Surg Res 2019; 233: 284–296

[28] Mehdinezhad Roshan M , Moharrami Kasmaie F , Kazemi Ashtiani M , Abdollahifar MA , Erfanian S , Zarkesh I , Nasiry D , Piryaei A . Human amniotic membrane extracellular matrix-derived scaffold modulates the number of mast cells in the granulation tissue and accelerates skin wound healing in diabetic rats. J Mazandaran Univ Med Sci 2023; 33(227): 11–24

[29] Liew PX , Kubes P . The neutrophil’s role during health and disease. Physiol Rev 2019; 99(2): 1223–1248

[30] Kaufmann SH . Immunity to intracellular bacteria. Annu Rev Immunol 1993; 11(1): 129–163

[31] Levy O . Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes. J Leukoc Biol 2004; 76(5): 909–925

[32] Segal AW . How neutrophils kill microbes. Annu Rev Immunol 2005; 23(1): 197–223

[33] Burn GL , Foti A , Marsman G , Patel DF , Zychlinsky A . The Neutrophil. Immunity 2021; 54(7): 1377–1391

[34] Wong SL , Demers M , Martinod K , Gallant M , Wang Y , Goldfine AB , Kahn CR , Wagner DD . Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat Med 2015; 21(7): 815–819

[35] Mikhalchik EV , Maximov DI , Ostrovsky EM , Yaskevich AV , Vlasova II , Vakhrusheva TV , Basyreva LY , Gusev AA , Kostevich VA , Gorbunov NP , Sokolov AV , Panasenko OM , Gusev SA . Neutrophils as a source of factors increasing duration of the inflammatory phase of wound healing in patients with type 2 diabetes mellitus. Biochem (Mosc) Suppl Ser B Biomed Chem 2019; 13(1): 68–73

[36] Tang Y , Liu L , Jie R , Tang Y , Zhao X , Xu M , Chen M . Negative pressure wound therapy promotes wound healing of diabetic foot ulcers by up-regulating PRDX2 in wound margin tissue. Sci Rep 2023; 13(1): 16192

[37] Serban D , Papanas N , Dascalu AM , Kempler P , Raz I , Rizvi AA , Rizzo M , Tudor C , Silviu Tudosie M , Tanasescu D , Pantea Stoian A , Gouveri E , Ovidiu Costea D . Significance of neutrophil to lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in diabetic foot ulcer and potential new therapeutic targets. Int J Low Extrem Wounds 2024; 23(2): 205–216

[38] Sawaya AP , Stone RC , Brooks SR , Pastar I , Jozic I , Hasneen K , O’Neill K , Mehdizadeh S , Head CR , Strbo N , Morasso MI , Tomic-Canic M . Deregulated immune cell recruitment orchestrated by FOXM1 impairs human diabetic wound healing. Nat Commun 2020; 11: 4678

[39] Pessoa AF , Florim JC , Rodrigues HG , Andrade-Oliveira V , Teixeira SA , Vitzel KF , Curi R , Saraiva Câmara NO , Muscará MN , Lamers ML , Santos MF . Oral administration of antioxidants improves skin wound healing in diabetic mice. Wound Repair Regen 2016; 24(6): 981–993

[40] Haineng W , Kang G , Jing W , Aibing X . Platelet-rich fibrin combined with curcumin nanoparticle hydrogel promotes wound healing in diabetic mice. Chinese Journal of Tissue Engineering Research 2022; 26(27): 4300–4307

[41] Yang P , Wang X , Wang D , Shi Y , Zhang M , Yu T , Liu D , Gao M , Zhang X , Liu Y . Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization. J Cell Sci 2021; 133(19): jcs235838

[42] Huang JJ , Yao Y , Xia CJ , Zhao YD , Yu S , Gao Y , Ye GH , Yu LS , Fan YY . Relationship between the number of neutrophils and myofibroblasts during diabetic wound healing and wound age. J Forensic Med (Fa Yi Xue Za Zhi) 2019; 35(2): 149–153

[43] Roy R , Zayas J , Singh SK , Delgado K , Wood SJ , Mohamed MF , Frausto DM , Albalawi YA , Price TP , Estupinian R , Giurini EF , Kuzel TM , Zloza A , Reiser J , Shafikhani SH . Overriding impaired FPR chemotaxis signaling in diabetic neutrophil stimulates infection control in murine diabetic wound. eLife 2022; 11: e72071

[44] Wang Q , Zhu G , Cao X , Dong J , Song F , Niu Y . Blocking AGE-RAGE signaling improved functional disorders of macrophages in diabetic wound. J Diabetes Res 2017; 2017: 1428537

[45] Wang Q , Cao X , Zhu G , Xie T , Ge K , Niu Y . Blockade of receptor for advanced glycation end products improved essential response of inflammation in diabetic wound healing. Int J Diabetes Dev Ctries 2020; 40(2): 283–289

[46] Ou YL. Acceleration of cutaneous wound healing in diabetic mouse by overexpression of Hpgds in adipose-derived stem cell seeded in hydrogel. Doctoral dissertation. Beijing: Peking Union Medical College, 2020

[47] Ma J , Song R , Liu C , Cao G , Zhang G , Wu Z , Zhang H , Sun R , Chen A , Wang Y , Yin S . Single-cell RNA-Seq analysis of diabetic wound macrophages in STZ-induced mice. J Cell Commun Signal 2023; 17(1): 103–120

[48] Joshi N , Pohlmeier L , Ben-Yehuda Greenwald M , Haertel E , Hiebert P , Kopf M , Werner S . Comprehensive characterization of myeloid cells during wound healing in healthy and healing-impaired diabetic mice. Eur J Immunol 2020; 50(9): 1335–1349

[49] Raghavan JV , Dorai VK , Sagar SK , Sivaraman A , R KS , Jhunjhunwala S . Immunomodulatory bandage for accelerated healing of diabetic wounds. ACS Bio Med Chem Au 2022; 2(4): 409–418

[50] Gu C , Fang Y , Ni T , Yu WR , Xu P , Wang Y , Cheng RJ . Expression of two chemokines during wound healing in diabetic mice. Chin J Burns (Zhonghua Shao Shang Za Zhi) 2008; 24(3): 221–222

[51] Fang L , Chen L , Song M , He J , Zhang L , Li C , Wang Q , Yang W , Sun W , Leng Y , Shi H , Wang S , Gao X , Wang H . Naoxintong accelerates diabetic wound healing by attenuating inflammatory response. Pharm Biol 2021; 59(1): 252–261

[52] Yang S , Gu Z , Lu C , Zhang T , Guo X , Xue G , Zhang L . Neutrophil extracellular traps are markers of wound healing impairment in patients with diabetic foot ulcers treated in a multidisciplinary setting. Adv Wound Care (New Rochelle) 2020; 9(1): 16–27

[53] Yang S , Wang S , Chen L , Wang Z , Chen J , Ni Q , Guo X , Zhang L , Xue G . Neutrophil extracellular traps delay diabetic wound healing by inducing endothelial-to-mesenchymal transition via the hippo pathway. Int J Biol Sci 2023; 19(1): 347–361

[54] Ibrahim I , Nuermaimaiti Y , Maimaituxun G , Luo X , Maimaituxun M , Akbar A , Tuerxun K , Wu Y . Neutrophil extracellular traps (NETs) are associated with type 2 diabetes and diabetic foot ulcer related amputation: a prospective cohort study. Diabetes Ther 2024; 15(6): 1333–1348

[55] Yang PL. Neutrophils extracellualar traps caused diabetic impaired wound healing and its mechanism. Doctoral dissertation. Shanghai: Shanghai Jiao Tong University, 2017

[56] Li H , Xu L , Chen J , Huang H , Liang F , Li S , Huang F , Guo J . Neutrophil extracellular trap formation suppressed by Ro 106–9920 enhances diabetic wound healing by blocking NLRP3 inflammasome activation. Front Biosci (Landmark Ed) 2025; 30(5): 37393

[57] Tsilingiris D , Natsi AM , Gavriilidis E , Antoniadou C , Eleftheriadou I , Anastasiou IA , Tentolouris A , Papadimitriou E , Eftalitsidis E , Kolovos P , Tsironidou V , Giatromanolaki A , Koffa M , Tentolouris N , Skendros P , Ritis K . Interleukin-8/matrix metalloproteinase-9 axis impairs wound healing in type 2 diabetes through neutrophil extracellular traps-fibroblast crosstalk. Eur J Immunol 2025; 55(4): e202451664

[58] Zhao H , Liu Y . Neutrophil extracellular traps induce fibroblast ferroptosis via IRE1α/XBP1-mediated ER stress to impair diabetic wound healing. Free Radic Biol Med 2025; 236: 17–27

[59] Xie Y , Yang J , Zhu H , Yang R , Fan Y . The efferocytosis dilemma: how neutrophil extracellular traps and PI3K/Rac1 complicate diabetic wound healing. Cell Commun Signal 2025; 23(1): 103

[60] Liu D , Yang P , Gao M , Yu T , Shi Y , Zhang M , Yao M , Liu Y , Zhang X . NLRP3 activation induced by neutrophil extracellular traps sustains inflammatory response in the diabetic wound. Clin Sci (Lond) 2019; 133(4): 565–582

[61] Scoville SD , Freud AG , Caligiuri MA . Modeling human natural killer cell development in the era of innate lymphoid cells. Front Immunol 2017; 8: 360

[62] Di Vito C , Mikulak J , Zaghi E , Pesce S , Marcenaro E , Mavilio D . NK cells to cure cancer. Semin Immunol 2019; 41: 101272

[63] Eberl G , Colonna M , Di Santo JP , McKenzie AN . Innate lymphoid cells: a new paradigm in immunology. Science 2015; 348(6237): aaa6566

[64] Vivier E , Ugolini S , Blaise D , Chabannon C , Brossay L . Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 2012; 12(4): 239–252

[65] Cavalcante-Silva J , Koh TJ . Role of NK cells in skin wound healing of Mice. J Immunol 2023; 210(7): 981–990

[66] Sobecki M , Krzywinska E , Nagarajan S , Audigé A , Huỳnh K , Zacharjasz J , Debbache J , Kerdiles Y , Gotthardt D , Takeda N , Fandrey J , Sommer L , Sexl V , Stockmann C . NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence. Nat Commun 2021; 12(1): 4700

[67] Zhu WP , Ying YF . A study on the correlation between diabetic foot and T lymphocyte subsets. Zhejiang Med J (Zhejiang Yi Xue Za Zhi) 2011; 33(2): 220–221

[68] Cheng Y , Ren L , Niyazi A , Sheng L , Zhao Y . Identification of potential immunologic resilience in the healing process of diabetic foot ulcers. Int Wound J 2023; 21(3): e14465

[69] Ouyang L , Qiu D , Fu X , Wu A , Yang P , Yang Z , Wang Q , Yan L , Xiao R . Overexpressing HPGDS in adipose-derived mesenchymal stem cells reduces inflammatory state and improves wound healing in type 2 diabetic mice. Stem Cell Res Ther 2022; 13(1): 395

[70] Zhou H , Yang XS , Liao CL , Zhang WC . Analysis on characteristics of diabetic foot ulceration-related genes and immune cells. J Shanghai Jiaotong Univ (Med Sci) (Shanghai Jiao Tong Da Xue Xue Bao (Yi Xue Ban)) 2020; 40(10): 1354–1359

[71] Jiang N , Xu C , Xu Y , Zhuo Y , Chen P , Deng S , Zhao Z , Long Y , Bai X , Wang Q , Chen Q . Comprehensive transcriptomic analysis of immune-related genes in diabetic foot ulcers: new insights into mechanisms and therapeutic targets. Int Immunopharmacol 2024; 139: 112638

[72] McGrath KE , Frame JM , Palis J . Early hematopoiesis and macrophage development. Semin Immunol 2015; 27(6): 379–387

[73] Ginhoux F , Guilliams M . Tissue-resident macrophage ontogeny and homeostasis. Immunity 2016; 44(3): 439–449

[74] Hashimoto D , Chow A , Noizat C , Teo P , Beasley MB , Leboeuf M , Becker CD , See P , Price J , Lucas D , Greter M , Mortha A , Boyer SW , Forsberg EC , Tanaka M , van Rooijen N , García-Sastre A , Stanley ER , Ginhoux F , Frenette PS , Merad M . Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 2013; 38(4): 792–804

[75] Auffray C , Fogg D , Garfa M , Elain G , Join-Lambert O , Kayal S , Sarnacki S , Cumano A , Lauvau G , Geissmann F . Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 2007; 317(5838): 666–670

[76] Dai XR , Zhang R , Yu YL , Miao HL . Expression of inflammatory factors and Toll-like receptors signaling pathways in diabetic foot infection patients and their significance. Chin J Nosocomiol (Zhonghua Yi Yuan Gan Ran Xue Za Zhi) 2020; 30(2): 198–202

[77] Li Z , Jian Y , Wei Z . Association between monocyte to lymphocyte ratio and diabetic foot ulcer in the population of the US with diabetes based on the 1999–2004 National Health and Nutrition Examination Survey data: a retrospective cross-sectional study. Front Endocrinol (Lausanne) 2024; 15: 1361393

[78] Zeng L , Zhang P , Fang Z , Liu D , Li H , Qu X , Chu S , Zhao H , Liu X , Lee M . The construction and analysis of infiltrating immune cell and ceRNA networks in diabetic foot ulcer. Front Endocrinol (Lausanne) 2022; 13: 836152

[79] Chen J , Liu Qw , Han Xy , Liu X , Lin Y , Ma Hk , He Xj , Li P . Effect of Huiyang-Shengji decoction on wound healing of chronic skin ulcer and phenotypic transformation of mononuclear phagocytes in dia-betic mice. Chin J Pathophysiol (Zhongguo Bing Li Sheng Li Za Zhi) 2021; 37(6): 1055–1066

[80] Ramalho T , Filgueiras L , Silva-Jr IA , Pessoa AFM , Jancar S . Impaired wound healing in type 1 diabetes is dependent on 5-lipoxygenase products. Sci Rep 2018; 8(1): 14164

[81] Mu R , Zhang Z , Han C , Niu Y , Xing Z , Liao Z , Xu J , Shao N , Chen G , Zhang J , Dong L , Wang C . Tumor-associated macrophages-educated reparative macrophages promote diabetic wound healing. EMBO Mol Med 2023; 15(2): e16671

[82] Chen J , Ma H , Meng Y , Liu Q , Wang Y , Lin Y , Yang D , Yao W , Wang Y , He X , Li P . Analysis of the mechanism underlying diabetic wound healing acceleration by Calycosin-7-glycoside using network pharmacology and molecular docking. Phytomedicine 2023; 114: 154773

[83] Barman PK , Urao N , Koh TJ . Diabetes induces myeloid bias in bone marrow progenitors associated with enhanced wound macrophage accumulation and impaired healing. J Pathol 2019; 249(4): 435–446

[84] Kimball A , Schaller M , Joshi A , Davis FM , denDekker A , Boniakowski A , Bermick J , Obi A , Moore B , Henke PK , Kunkel SL , Gallagher KA . Ly6C(Hi) blood monocyte/macrophage drive chronic inflammation and impair wound healing in diabetes mellitus. Arterioscler Thromb Vasc Biol 2018; 38(5): 1102–1114

[85] Olingy CE , San Emeterio CL , Ogle ME , Krieger JR , Bruce AC , Pfau DD , Jordan BT , Peirce SM , Botchwey EA . Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury. Sci Rep 2017; 7(1): 447

[86] Crane MJ , Daley JM , van Houtte O , Brancato SK , Henry WL Jr , Albina JE . The monocyte to macrophage transition in the murine sterile wound. PLoS One 2014; 9(1): e86660

[87] Mirza RE , Koh TJ . Contributions of cell subsets to cytokine production during normal and impaired wound healing. Cytokine 2015; 71(2): 409–412

[88] Pang J , Maienschein-Cline M , Koh TJ . Enhanced proliferation of Ly6C⁺ monocytes/macrophages contributes to chronic inflammation in skin wounds of diabetic mice. J Immunol 2021; 206(3): 621–630

[89] Pang J , Maienschein-Cline M , Koh TJ . Reduced apoptosis of monocytes and macrophages is associated with their persistence in wounds of diabetic mice. Cytokine 2021; 142: 155516

[90] Mirza R , Koh TJ . Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice. Cytokine 2011; 56(2): 256–264

[91] Yang H , Xu H , Wang Z , Li X , Wang P , Cao X , Xu Z , Lv D , Rong Y , Chen M , Tang B , Hu Z , Deng W , Zhu J . Analysis of miR-203a-3p/SOCS3-mediated induction of M2 macrophage polarization to promote diabetic wound healing based on epidermal stem cell-derived exosomes. Diabetes Res Clin Pract 2023; 197: 110573

[92] Wang J , Han Y , Huang F , Tang L , Mu J , Liang Y . Diabetic macrophage small extracellular vesicles-associated miR-503/IGF1R axis regulates endothelial cell function and affects wound healing. Front Immunol 2023; 14: 1104890

[93] Gallagher KA , Joshi A , Carson WF , Schaller M , Allen R , Mukerjee S , Kittan N , Feldman EL , Henke PK , Hogaboam C , Burant CF , Kunkel SL . Epigenetic changes in bone marrow progenitor cells influence the inflammatory phenotype and alter wound healing in type 2 diabetes. Diabetes 2015; 64(4): 1420–1430

[94] Paige JT , Kremer M , Landry J , Hatfield SA , Wathieu D , Brug A , Lightell DJ , Spiller KL , Woods TC . Modulation of inflammation in wounds of diabetic patients treated with porcine urinary bladder matrix. Regen Med 2019; 14(4): 269–277

[95] Bannon P , Wood S , Restivo T , Campbell L , Hardman MJ , Mace KA . Diabetes induces stable intrinsic changes to myeloid cells that contribute to chronic inflammation during wound healing in mice. Dis Model Mech 2013; 6(6): 1434–1447

[96] Theocharidis G , Thomas BE , Sarkar D , Mumme HL , Pilcher WJR , Dwivedi B , Sandoval-Schaefer T , Sîrbulescu RF , Kafanas A , Mezghani I , Wang P , Lobao A , Vlachos IS , Dash B , Hsia HC , Horsley V , Bhasin SS , Veves A , Bhasin M . Single cell transcriptomic landscape of diabetic foot ulcers. Nat Commun 2022; 13(1): 181

[97] Li Y , Li X , Ju S , Li W , Zhou S , Wang G , Cai Y , Dong Z . Role of M1 macrophages in diabetic foot ulcers and related immune regulatory mechanisms. Front Pharmacol 2022; 13: 1098041

[98] Liu Z , Bian X , Luo L , Björklund ÅK , Li L , Zhang L , Chen Y , Guo L , Gao J , Cao C , Wang J , He W , Xiao Y , Zhu L , Annusver K , Gopee NH , Basurto-Lozada D , Horsfall D , Bennett CL , Kasper M , Haniffa M , Sommar P , Li D , Landén NX . Spatiotemporal single-cell roadmap of human skin wound healing. Cell Stem Cell 2025; 32(3): 479–498.e8

[99] Song J , Zeng J , Zheng S , Jiang N , Wu A , Guo S , Ye R , Hu L , Huang F , Wang L , Xiaogang Z , Liu B , Wu J , Chen Q . Sanguisorba officinalis L. promotes diabetic wound healing in rats through inflammation response mediated by macrophage. Phytother Res 2023; 37(9): 4265–4281

[100] Liu Y , Xia G , Chen Y , Xia H , Xu J , Guo L , Lin S , Liu Y . Purpurolide C-based microneedle promotes macrophage-mediated diabetic wound healing via inhibiting TLR4–MD2 dimerization and MYD88 phosphorylation. Acta Pharm Sin B 2023; 13(12): 5060–5073

[101] Geng K , Ma X , Jiang Z , Gu J , Huang W , Wang W , Xu Y , Xu Y . WDR74 facilitates TGF-β/Smad pathway activation to promote M2 macrophage polarization and diabetic foot ulcer wound healing in mice. Cell Biol Toxicol 2023; 39(4): 1577–1591

[102] Pang L , Liao Q , Zou L , Zhang C , Nie X , Yi Z , Fu C , Zhang J . Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. Int J Biol Macromol 2022; 209(Pt B): 2130–2141

[103] Miao MY. The role and mechanism of macrophage activation in diabetic wound healing. Doctoral dissertation. Shanghai: Shanghai Jiao Tong University, 2012

[104] Hozzein WN , Badr G , Badr BM , Allam A , Al Ghamdi A , Al-Wadaan MA , Al-Waili NS . Bee venom improves diabetic wound healing by protecting functional macrophages from apoptosis and enhancing Nrf2, Ang-1 and Tie-2 signaling. Mol Immunol 2018; 103: 322–335

[105] Yan J , Tie G , Wang S , Tutto A , DeMarco N , Khair L , Fazzio TG , Messina LM . Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages. Nat Commun 2018; 9(1): 33

[106] Sharma S , Kishen A . Dysfunctional crosstalk between macrophages and fibroblasts under LPS-infected and hyperglycemic environment in diabetic wounds. Sci Rep 2025; 15(1): 17233

[107] Cai Y , Chen K , Liu C , Qu X . Harnessing strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns. Bioact Mater 2023; 28: 243–254

[108] Joorabloo A , Liu T . Recent advances in nanomedicines for regulation of macrophages in wound healing. J Nanobiotechnology 2022; 20(1): 407

[109] Ellis S , Lin EJ , Tartar D . Immunology of wound healing. Curr Dermatol Rep 2018; 7(4): 350–358

[110] Shi R , Jin Y , Zhao S , Yuan H , Shi J , Zhao H . Hypoxic ADSC-derived exosomes enhance wound healing in diabetic mice via delivery of circ-Snhg11 and induction of M2-like macrophage polarization. Biomed Pharmacother 2022; 153: 113463

[111] Zhang X , Dai J , Li L , Chen H , Chai Y . NLRP3 inflammasome expression and signaling in human diabetic wounds and in high glucose induced macrophages. J Diabetes Res 2017; 2017: 5281358

[112] Wang Y , Jing L , Lei X , Ma Z , Li B , Shi Y , Zhang W , Li Y , Zhou H , Hu K , Xue Y , Jin Y . Umbilical cord mesenchymal stem cell-derived apoptotic extracellular vesicles ameliorate cutaneous wound healing in type 2 diabetic mice via macrophage pyroptosis inhibition. Stem Cell Res Ther 2023; 14(1): 257

[113] Tang Y , Zhang MJ , Hellmann J , Kosuri M , Bhatnagar A , Spite M . Proresolution therapy for the treatment of delayed healing of diabetic wounds. Diabetes 2013; 62(2): 618–627

[114] Dardenne C , Salon M , Authier H , Meunier E , AlaEddine M , Bernad J , Bouschbacher M , Lefèvre L , Pipy B , Coste A . Topical aspirin administration improves cutaneous wound healing in diabetic mice through a phenotypic switch of wound macrophages toward an anti-inflammatory and proresolutive profile characterized by LXA4 release. Diabetes 2022; 71(10): 2181–2196

[115] Hou XL. The preliminary research on the interaction of diabetic foot infection and autophagy. Master’s thesis. Tianjin: Tianjin Medical University, 2016

[116] Khanna S , Biswas S , Shang Y , Collard E , Azad A , Kauh C , Bhasker V , Gordillo GM , Sen CK , Roy S . Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One 2010; 5(3): e9539

[117] Chorro L , Sarde A , Li M , Woollard KJ , Chambon P , Malissen B , Kissenpfennig A , Barbaroux JB , Groves R , Geissmann F . Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J Exp Med 2009; 206(13): 3089–3100

[118] Kashem SW , Haniffa M , Kaplan DH . Antigen-presenting cells in the skin. Annu Rev Immunol 2017; 35(1): 469–499

[119] Seneschal J , Clark RA , Gehad A , Baecher-Allan CM , Kupper TS . Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells. Immunity 2012; 36(5): 873–884

[120] Lenz A , Heine M , Schuler G , Romani N . Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization. J Clin Invest 1993; 92(6): 2587–2596

[121] Vinish M , Cui W , Stafford E , Bae L , Hawkins H , Cox R , Toliver-Kinsky T . Dendritic cells modulate burn wound healing by enhancing early proliferation. Wound Repair Regen 2016; 24(1): 6–13

[122] Strbo N , Yin N , Stojadinovic O . Innate and adaptive immune responses in wound epithelialization. Adv Wound Care (New Rochelle) 2014; 3(7): 492–501

[123] Wasko R , Bridges K , Pannone R , Sidhu I , Xing Y , Naik S , Miller-Jensen K , Horsley V . Langerhans cells are essential components of the angiogenic niche during murine skin repair. Dev Cell 2022; 57(24): 2699–713.e5

[124] Qian J , Park DJ , Perrott S , Patel P , Eliceiri BP . Genetic background and kinetics define wound bed extracellular vesicles in a mouse model of cutaneous injury. Int J Mol Sci 2021; 22(7): 3551

[125] Xia W , Zhu Z , Xiang S , Yang Y . Ginsenoside Rg5 promotes wound healing in diabetes by reducing the negative regulation of SLC7A11 on the efferocytosis of dendritic cells. J Ginseng Res 2023; 47(6): 784–794

[126] Maschalidi S , Mehrotra P , Keçeli BN , De Cleene HKL , Lecomte K , Van der Cruyssen R , Janssen P , Pinney J , van Loo G , Elewaut D , Massie A , Hoste E , Ravichandran KS . Targeting SLC7A11 improves efferocytosis by dendritic cells and wound healing in diabetes. Nature 2022; 606(7915): 776–784

[127] Gong X , Cai J , Zheng W , Huang J , Chen T , Chen W , Zheng X . Isoliquiritigenin alleviates SLC7A11-mediated efferocytosis inhibition to promote wounds healing in diabetes. Biomed Pharmacother 2024; 180: 117578

[128] Henn D , Zhao D , Sivaraj D , Trotsyuk A , Bonham CA , Fischer KS , Kehl T , Fehlmann T , Greco AH , Kussie HC , Moortgat Illouz SE , Padmanabhan J , Barrera JA , Kneser U , Lenhof HP , Januszyk M , Levi B , Keller A , Longaker MT , Chen K , Qi LS , Gurtner GC . Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing. Nat Commun 2023; 14(1): 4729

[129] Stojadinovic O , Yin N , Lehmann J , Pastar I , Kirsner RS , Tomic-Canic M . Increased number of Langerhans cells in the epidermis of diabetic foot ulcers correlates with healing outcome. Immunol Res 2013; 57(1-3): 222–228

[130] Galkowska H , Olszewski WL , Wojewodzka U . Expression of natural antimicrobial peptide beta-defensin-2 and Langerhans cell accumulation in epidermis from human non-healing leg ulcers. Folia Histochem Cytobiol 2005; 43(3): 133–136

[131] Rajesh A , Stuart G , Real N , Ahn J , Tschirley A , Wise L , Hibma M . Depletion of langerin⁺ cells enhances cutaneous wound healing. Immunology 2020; 160(4): 366–381

[132] Ishida I , Verbeek S , Bonneville M , Itohara S , Berns A , Tonegawa S . T-cell receptor gamma delta and gamma transgenic mice suggest a role of a gamma gene silencer in the generation of alpha beta T cells. Proc Natl Acad Sci USA 1990; 87(8): 3067–3071

[133] Moura J , Rodrigues J , Goncalves M , Amaral C , Lima M , Carvalho E . Impaired T-cell differentiation in diabetic foot ulceration. Cell Mol Immunol 2017; 14(9): 758–769

[134] Galkowska H , Wojewodzka U , Olszewski WL . Low recruitment of immune cells with increased expression of endothelial adhesion molecules in margins of the chronic diabetic foot ulcers. Wound Repair Regen 2005; 13(3): 248–254

[135] Banerjee D , Paul S , Selvan C , Pai S , Nandakumar BS , Mukherjee S , Raghavendra PB . Uncovering the role of tertiary lymphoid organs in the inflammatory landscape: a novel immunophenotype of diabetic foot ulcers. J Cell Mol Med 2025; 29(7): e70479

[136] Wang YF , Que HF . Substantial foundation of pathogenesis of qi-insuffifiency and blood-stasis in diabetic foot gangrene. Chin J Surg Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 2010; 16(04): 406–409

[137] Loots MA , Lamme EN , Zeegelaar J , Mekkes JR , Bos JD , Middelkoop E . Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol 1998; 111(5): 850–857

[138] Sun L , Su Y , Jiao A , Wang X , Zhang B . T cells in health and disease. Signal Transduct Target Ther 2023; 8(1): 235

[139] Koch U , Radtke F . Mechanisms of T cell development and transformation. Annu Rev Cell Dev Biol 2011; 27(1): 539–562

[140] Davis PA , Corless DJ , Aspinall R , Wastell C . Effect of CD4⁺ and CD8⁺ cell depletion on wound healing. Br J Surg 2001; 88(2): 298–304

[141] Wang S , Zhang Y , Wang Y , Ye P , Li J , Li H , Ding Q , Xia J . Amphiregulin confers regulatory T cell suppressive function and tumor invasion via the EGFR/GSK-3β/Foxp3 axis. J Biol Chem 2016; 291(40): 21085–21095

[142] Zaiss DM , van Loosdregt J , Gorlani A , Bekker CP , Gröne A , Sibilia M , van Bergen en Henegouwen PM , Roovers RC , Coffer PJ , Sijts AJ . Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor. Immunity 2013; 38(2): 275–284

[143] Zaiss DM , Minutti CM , Knipper JA . Immune- and non-immune-mediated roles of regulatory T-cells during wound healing. Immunology 2019; 157(3): 190–197

[144] Zhang J , Chen J , Gao C , Sun X , Wang L , Hu Z , Li G , Wang J , Wang A . Maggot treatment promotes healing of diabetic foot ulcer wounds possibly by upregulating Treg levels. Diabetes Res Clin Pract 2022; 184: 109187

[145] Zoheir KMA , Ali NI , Ashour AE , Kishta MS , Othman SI , Rudayni HA , Rashad AA , Allam AA . Lipoic acid improves wound healing through its immunomodulatory and anti-inflammatory effects in a diabetic mouse model. J Diabetes Metab Disord 2025; 24(1): 56

[146] Barros JF , Waclawiak I , Pecli C , Borges PA , Georgii JL , Ramos-Junior ES , Canetti C , Courau T , Klatzmann D , Kunkel SL , Penido C , Canto FB , Benjamim CF . Role of chemokine receptor CCR4 and regulatory T cells in wound healing of diabetic mice. J Invest Dermatol 2019; 139(5): 1161–1170

[147] Mi T , Yu R , Su LQ , Zou XL , Liu X , Wu YJ . Effect of Shuyu pill combined Longxuejie capsules on wound healing in MKR type 2 diabetic mice. Chin J Surg Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 2019; 39(9): 1110–1115

[148] Liu Y , Wang P , Li J , Chen L , Shu B , Wang H , Liu H , Zhao S , Zhou J , Chen X , Xie J . Single-cell RNA sequencing reveals the impaired epidermal differentiation and pathological microenvironment in diabetic foot ulcer. Burns Trauma 2025; 13: tkae065

[149] Hu Y , Hu Q , Li Y , Lu L , Xiang Z , Yin Z , Kabelitz D , Wu Y . γδ T cells: origin and fate, subsets, diseases and immunotherapy. Signal Transduct Target Ther 2023; 8(1): 434

[150] Hu W , Shang R , Yang J , Chen C , Liu Z , Liang G , He W , Luo G . Skin γδ T cells and their function in wound healing. Front Immunol 2022; 13: 875076

[151] Li Y , Wu J , Luo G , He W . Functions of Vγ4 T cells and dendritic epidermal T cells on skin wound healing. Front Immunol 2018; 9: 1099

[152] Xu P , Fu X , Xiao N , Guo Y , Pei Q , Peng Y , Zhang Y , Yao M . Involvements of γδT lymphocytes in acute and chronic skin wound repair. Inflammation 2017; 40(4): 1416–1427

[153] Wei T , Pan T , Peng X , Zhang M , Guo R , Guo Y , Mei X , Zhang Y , Qi J , Dong F , Han M , Kong F , Zou L , Li D , Zhi D , Wu W , Kong D , Zhang S , Zhang C . Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds. Nat Nanotechnol 2024; 19(8): 1178–1189

[154] Liu Z , Xu Y , Zhang X , Liang G , Chen L , Xie J , Tang J , Zhao J , Shu B , Qi S , Chen J , Luo G , Wu J , He W , Liu X . Defects in dermal Vγ4 γ δ T cells result in delayed wound healing in diabetic mice. Am J Transl Res 2016; 8(6): 2667–2680

[155] Liu Z , Xu Y , Chen L , Xie J , Tang J , Zhao J , Shu B , Qi S , Chen J , Liang G , Luo G , Wu J , He W , Liu X . Dendritic epidermal T cells facilitate wound healing in diabetic mice. Am J Transl Res 2016; 8(5): 2375–2384

[156] Wang Y , Bai Y , Li Y , Liang G , Jiang Y , Liu Z , Liu M , Hao J , Zhang X , Hu X , Chen J , Wang R , Yin Z , Wu J , Luo G , He W . IL-15 enhances activation and IGF-1 production of dendritic epidermal T cells to promote wound healing in diabetic mice. Front Immunol 2017; 8: 1557

[157] Iwata Y , Yoshizaki A , Komura K , Shimizu K , Ogawa F , Hara T , Muroi E , Bae S , Takenaka M , Yukami T , Hasegawa M , Fujimoto M , Tomita Y , Tedder TF , Sato S . CD19, a response regulator of B lymphocytes, regulates wound healing through hyaluronan-induced TLR4 signaling. Am J Pathol 2009; 175(2): 649–660

[158] Sîrbulescu RF , Boehm CK , Soon E , Wilks MQ , Ilieş I , Yuan H , Maxner B , Chronos N , Kaittanis C , Normandin MD , El Fakhri G , Orgill DP , Sluder AE , Poznansky MC . Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions. Wound Repair Regen 2017; 25(5): 774–791

[159] Yin Y , Wu S . B cells recruitment promotes M2 macrophage polarization to inhibit inflammation during wound healing. Clin Exp Immunol 2025; 219(1): uxaf002

[160] Radzieta M , Peters TJ , Dickson HG , Cowin AJ , Lavery LA , Schwarzer S , Roberts T , Jensen SO , Malone M . A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers. Acta Pathol Microbiol Scand Suppl 2022; 130(7): 383–396

[161] Zhang K , Ding S , Lyu X , Tan Q , Wang Z . Correlation between the platelet-to-lymphocyte ratio and diabetic foot ulcer in patients with type 2 diabetes mellitus. J Clin Lab Anal 2021; 35(4): e23719

[162] Oncul O , Yildiz S , Gurer US , Yeniiz E , Qyrdedi T , Top C , Gocer P , Akarsu B , Cevikbas A , Cavuslu S . Effect of the function of polymorphonuclear leukocytes and interleukin-1 beta on wound healing in patients with diabetic foot infections. J Infect 2007; 54(3): 250–256

[163] Burger B , Sagiorato RN , Silva JR , Candreva T , Pacheco MR , White D , Castelucci BG , Pral LP , Fisk HL , Rabelo ILA , Elias-Oliveira J , Osório WR , Consonni SR , Farias ADS , Vinolo MAR , Lameu C , Carlos D , Fielding BA , Whyte MB , Martinez FO , Calder PC , Rodrigues HG . Eicosapentaenoic acid-rich oil supplementation activates PPAR-γ and delays skin wound healing in type 1 diabetic mice. Front Immunol 2023; 14: 1141731

[164] Cantaruti T , Costa RA , Franco-Valencia K , Nóbrega IBC , Galdino DADA , Vaz NM , Carvalho CR . Parenteral re-exposure to an immunologically tolerated protein up to 6h after skin injuries improves wound healing in diabetic mice. J Immunol Regen Med 2019; 6: 100022

[165] Huang W , Jiao J , Liu J , Huang M , Hu Y , Ran W , Yan L , Xiong Y , Li M , Quan Z , Rao Y , Chen J , Huang Y , Zhang D . MFG-E8 accelerates wound healing in diabetes by regulating “NLRP3 inflammasome-neutrophil extracellular traps” axis. Cell Death Discov 2020; 6(1): 84

[166] Śitum K , Bokulić A , Ivetić-Tkalčević V , Parnham MJ , Čužić S , Durić K , Glojnarić I , Ševeljević D , Brajša K . Comparison of systemic inflammatory and hematology parameters in normal C57B1/6 and genetically diabetic db/db mice during local wound repair. Biochem Med (Zagreb) 2007; 17(1): 85–93

[167] Seraphim PM , Leal EC , Moura J , Goncalves P , Goncalves JP , Carvalho E . Lack of lymphocytes impairs macrophage polarization and angiogenesis in diabetic wound healing. Life Sci 2020; 254: 117813

[168] Tellechea A , Bai S , Dangwal S , Theocharidis G , Nagai M , Koerner S , Cheong JE , Bhasin S , Shih TY , Zheng Y , Zhao W , Zhang C , Li X , Kounas K , Panagiotidou S , Theoharides T , Mooney D , Bhasin M , Sun L , Veves A . Topical application of a mast cell stabilizer improves impaired diabetic wound healing. J Invest Dermatol 2020; 140(4): 901–11.e11

[169] Babaei S , Ansarihadipour H , Nakhaei M , Darabi M , Bayat P , Sakhaei M , Baazm M , Mohammadhoseiny A . Effect of Omegaven on mast cell concentration in diabetic wound healing. J Tissue Viability 2017; 26(2): 125–130

[170] Huang YY , Lin CW , Cheng NC , Cazzell SM , Chen HH , Huang KF , Tung KY , Huang HL , Lin PY , Perng CK , Shi B , Liu C , Ma Y , Cao Y , Li Y , Xue Y , Yan L , Li Q , Ning G , Chang SC . Effect of a novel macrophage-regulating drug on wound healing in patients with diabetic foot ulcers: a randomized clinical trial. JAMA Netw Open 2021; 4(9): e2122607

[171] Tao L , Wu S , Wang Q , Xi Z , Zou Y , Cao M , Liang K , Xu W , Hu Q , Ge Y , Yin Z , Ju Z , Liu Z . IL-27 accelerates diabetic wound healing by modulating macrophage polarization. Int Immunopharmacol 2025; 155: 114575

[172] Da Silva J , Figueiredo A , Tseng YH , Carvalho E , Leal EC . Bone morphogenetic protein 7 improves wound healing in diabetes by decreasing inflammation and promoting M2 macrophage polarization. Int J Mol Sci 2025; 26(5): 2036

[173] Geng K , Ma X , Jiang Z , Huang W , Gu J , Wang P , Luo L , Xu Y , Xu Y . High glucose-induced STING activation inhibits diabetic wound healing through promoting M1 polarization of macrophages. Cell Death Discov 2023; 9(1): 136

[174] Sun D , Chang Q , Lu F . Immunomodulation in diabetic wounds healing: the intersection of macrophage reprogramming and immunotherapeutic hydrogels. J Tissue Eng 2024; 15: 20417314241265202

[175] Meng H , Su J , Shen Q , Hu W , Li P , Guo K , Liu X , Ma K , Zhong W , Chen S , Ma L , Hao Y , Chen J , Jiang Y , Li L , Fu X , Zhang C . A smart MMP-9-responsive hydrogel releasing M2 macrophage-derived exosomes for diabetic wound healing. Adv Healthc Mater 2025; 14(10): 2404966

[176] Wrangle JM , Velcheti V , Patel MR , Garrett-Mayer E , Hill EG , Ravenel JG , Miller JS , Farhad M , Anderton K , Lindsey K , Taffaro-Neskey M , Sherman C , Suriano S , Swiderska-Syn M , Sion A , Harris J , Edwards AR , Rytlewski JA , Sanders CM , Yusko EC , Robinson MD , Krieg C , Redmond WL , Egan JO , Rhode PR , Jeng EK , Rock AD , Wong HC , Rubinstein MP . ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial. Lancet Oncol 2018; 19(5): 694–704

[177] Shan H , Wang X , Zhang J . Dendritic epidermal T cell hydrogel induces the polarization of M2 macrophages to promote the healing of deep tissue pressure injury. J Tissue Viability 2024; 33(3): 440–448

[178] Perrault DP , Bramos A , Xu X , Shi S , Wong AK . Local administration of interleukin-1 receptor antagonist improves diabetic wound healing. Ann Plast Surg 2018; 80(Suppl 5): S317–S321

[179] Goren I , Müller E , Pfeilschifter J , Frank S . Severely impaired insulin signaling in chronic wounds of diabetic ob/ob mice: a potential role of tumor necrosis factor-alpha. Am J Pathol 2006; 168(3): 765–777

[180] Streit M , Beleznay Z , Braathen LR . Topical application of the tumour necrosis factor-alpha antibody infliximab improves healing of chronic wounds. Int Wound J 2006; 3(3): 171–179

[181] Feng J , Dong C , Long Y , Mai L , Ren M , Li L , Zhou T , Yang Z , Ma J , Yan L , Yang X , Gao G , Qi W . Elevated Kallikrein-binding protein in diabetes impairs wound healing through inducing macrophage M1 polarization. Cell Commun Signal 2019; 17(1): 60

[182] Ishida Y , Kuninaka Y , Nosaka M , Furuta M , Kimura A , Taruya A , Yamamoto H , Shimada E , Akiyama M , Mukaida N , Kondo T . CCL2-mediated reversal of impaired skin wound healing in diabetic mice by normalization of neovascularization and Collagen accumulation. J Invest Dermatol 2019; 139(12): 2517–2527.e5

[183] Wang QM , Xu P , Fu YY , Pan YY . Exploring the mechanism of modified Simiao Yong’an Decoction for promoting diabetic foot ulcers healing in rats based on a new perspective of “LncRNA MALAT1-macrophage pyroptosis”. J Guangzhou Univ Tradit Chin Med (Guangzhou Zhong Yi Yao Da Xue Xue Bao) 2023; 40(2): 413–420

RIGHTS & PERMISSIONS

Higher Education Press