Diabetic Wound Repair: From Mechanism to Therapeutic Opportunities

Abstract

Diabetic wound healing, characterized by persistent inflammation, impaired angiogenesis, and dysfunctional cellular responses, remains a major clinical challenge due to its complex pathophysiology. This challenge is most evident in diabetic foot ulcers (DFUs), which carry high risks of infection, recurrence, and amputation, contributing substantially to patient morbidity, mortality, and healthcare costs. Despite multidisciplinary care, debridement, and advanced dressings, healing outcomes are often suboptimal, highlighting an urgent need for deeper pathophysiological insights and more effective therapeutic strategies. This review synthesizes current understanding of DFU pathogenesis, emphasizing how sustained metabolic dysfunction disrupts fibroblast and immune cell function, thereby perpetuating chronic wounds. We also critically examine commonly used animal models and their limitations in replicating the complexity of human DFUs and discuss emerging therapeutic approaches with translational promise. Advancing our understanding of these mechanisms and validating innovative interventions may ultimately reduce DFU-related amputations and mortality, improve healing outcomes, and enhance patient quality of life. This review aims to catalyze future research and therapeutic innovation in diabetic wound care.

Keywords

animal models / cellular dysfunction / diabetic wounds / emerging therapies / metabolic microenvironment

References

[1] O. A. Peña and P. Martin, “Cellular and Molecular Mechanisms of Skin Wound Healing,” Nature Reviews Molecular Cell Biology 25 (2024): 599-616.

[2] T. A. Harris-Tryon and E. A. Grice, “Microbiota and Maintenance of Skin Barrier Function,” Science 376 (2022): 940-945.

[3] R. T. Beyene, S. L. Derryberry, and A. Barbul, “The Effect of Comorbidities on Wound Healing,” Surgical Clinics of North America 100 (2020): 695-705.

[4] M. Kremer and N. Burkemper, “Aging Skin and Wound Healing,” Clinics in Geriatric Medicine 40 (2024): 1-10.

[5] A. Grada and T. J. Phillips, “Nutrition and Cutaneous Wound Healing,” Clinics in Dermatology 40 (2022): 103-113.

[6] V. Falanga, R. R. Isseroff, A. M. Soulika, et al., “Chronic Wounds,” Nature Reviews Disease Primers 8 (2022): 50.

[7] M. Polikandrioti, G. Vasilopoulos, I. Koutelekos, et al., “Depression in Diabetic Foot Ulcer: Associated Factors and the Impact of Perceived Social Support and Anxiety on Depression,” International Wound Journal 17 (2020): 900-909.

[8] P. Martin and R. Nunan, “Cellular and Molecular Mechanisms of Repair in Acute and Chronic Wound Healing,” British Journal of Dermatology 173 (2015): 370-378.

[9] Committee, A. D. A. P. P. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024. Diabetes Care 47, (2023): S20-S42.

[10] J. J. Van Netten, S. A. Bus, J. Apelqvist, et al., “Definitions and Criteria for Diabetes-Related Foot Disease (IWGDF 2023 update),” Diabetes/Metabolism Research and Reviews 40 (2024): e3654.

[11] H. Sun, P. Saeedi, S. Karuranga, et al., “IDF Diabetes Atlas: Global, Regional and Country-level Diabetes Prevalence Estimates for 2021 and Projections for 2045,” Diabetes Research and Clinical Practice 183 (2022): 109119.

[12] D. G. Armstrong, A. J. M. Boulton, and S. A. Bus, “Diabetic Foot Ulcers and Their Recurrence,” New England Journal of Medicine 376 (2017): 2367-2375.

[13] Y. Zhang, P. A. Lazzarini, S. M. Mcphail, J. J. Van Netten, D. G. Armstrong, and R. E. Pacella, “Global Disability Burdens of Diabetes-Related Lower-Extremity Complications in 1990 and 2016,” Diabetes Care 43 (2020): 964-974.

[14] A. Abid and S. Hosseinzadeh, StatPearls (StatPearls Publishing Copyright © 2025, StatPearls Publishing LLC., 2025).

[15] T. Maldonado-Valer, L. F. Pareja-Mujica, R. Corcuera-Ciudad, et al., “Prevalence of diabetic foot at Risk of Ulcer Development and Its Components Stratification According to the international working group on the diabetic foot (IWGDF): A Systematic Review With metanalysis,” PLoS ONE 18 (2023): e0284054.

[16] D. G. Armstrong, T. W. Tan, A. J. M. Boulton, and S. A. Bus, “Diabetic Foot Ulcers,” Jama 330 (2023): 62.

[17] M. Ndosi, A. Wright-Hughes, S. Brown, et al., “Prognosis of the Infected Diabetic Foot Ulcer: A 12-Month Prospective Observational Study,” Diabetic Medicine 35 (2018): 78-88.

[18] J. B. Rice, U. Desai, A. K. G. Cummings, H. G. Birnbaum, M. Skornicki, and N. B. Parsons, “Burden of Diabetic Foot Ulcers for medicare and Private Insurers,” Diabetes Care 37 (2014): 651-658.

[19] Q. Pan, S. Fei, L. Zhang, et al., “How Does Diabetic Peripheral Neuropathy Impact Patients' burden of Illness and the Economy? A Retrospective Study in Beijing, China,” Frontiers in Public Health 11 (2023): 1164536.

[20] F. Huang, X. Lu, Y. Yang, et al., “Microenvironment-Based Diabetic Foot Ulcer Nanomedicine,” Advanced Science 10 (2023): e2203308.

[21] H. Deng, B. Li, Q. Shen, et al., “Mechanisms of Diabetic Foot Ulceration: A Review,” Journal of Diabetes 15 (2023): 299-312.

[22] J. Holl, C. Kowalewski, Z. Zimek, et al., “Chronic Diabetic Wounds and Their Treatment With Skin Substitutes,” Cells 10 (2021): 655.

[23] E. Ahmad, S. Lim, R. Lamptey, D. R. Webb, and M. J. Davies, “Type 2 Diabetes,” The Lancet 400 (2022): 1803-1820.

[24] T. Quattrin, L. D. Mastrandrea, and L. S. K. Walker, “Type 1 Diabetes,” The Lancet 401 (2023): 2149-2162.

[25] P. González, P. Lozano, G. Ros, F. H. Solano, and O. Stress, “An Integral, Updated and Critical Overview of Their Metabolic Interconnections,” International Journal of Molecular Sciences 24 (2023).

[26] S. A. Ansari and B. S. Emerald, “The Role of Insulin Resistance and Protein O-GlcNAcylation in Neurodegeneration,” Frontiers in Neuroscience 13 (2019): 473.

[27] K. C. Nandipati, S. Subramanian, and D. K. Agrawal, “Protein Kinases: Mechanisms and Downstream Targets in Inflammation-mediated Obesity and Insulin Resistance,” Molecular and Cellular Biochemistry 426 (2017): 27-45.

[28] R. Testa, A. R. Bonfigli, F. Prattichizzo, L. La Sala, V. De Nigris, and A. Ceriello, “The “Metabolic Memory” Theory and the Early Treatment of Hyperglycemia in Prevention of Diabetic Complications,” Nutrients (2017): 9.

[29] S. S. Garg and J. Gupta, “Polyol Pathway and Redox Balance in Diabetes,” Pharmacological Research 182 (2022): 106326.

[30] N. Rabbani, M. Xue, and P. J. Thornalley, “Hexokinase-2-Linked Glycolytic Overload and Unscheduled Glycolysis—Driver of Insulin Resistance and Development of Vascular Complications of Diabetes,” International Journal of Molecular Sciences 23 (2022): 2165.

[31] H. Guo, K. Xiao, Y. Zheng, and J. Zong, “Integrating Bioinformatics and Multiple Machine Learning to Identify Mitophagy-related Targets for the Diagnosis and Treatment of Diabetic Foot Ulcers: Evidence From Transcriptome Analysis and Drug Docking,” Frontiers in Molecular Biosciences 11 (2024): 1420136.

[32] D. R. D'Souza, M. M. Salib, J. Bennett, et al., “Hyperglycemia Regulates RUNX2 Activation and Cellular Wound Healing Through the Aldose Reductase Polyol Pathway,” Journal of Biological Chemistry 284 (2009): 17947-17955.

[33] S. A. Kulkarni, S. K. Deshpande, and A. Rastogi, “Novel Topical Esmolol Hydrochloride Improves Wound Healing in Diabetes by Inhibiting Aldose Reductase, Generation of Advanced Glycation End Products, and Facilitating the Migration of Fibroblasts,” Frontiers in Endocrinology 13 (2022): 926129.

[34] O. Nakagaki, H. Miyoshi, T. Sawada, T. Atsumi, T. Kondo, and T. Atsumi, “Epalrestat Improves Diabetic Wound Healing via Increased Expression of Nerve Growth Factor,” Experimental and Clinical Endocrinology & Diabetes 121 (2013): 84-89.

[35] A. Paneque, H. Fortus, J. Zheng, G. Werlen, and E. Jacinto, “The Hexosamine Biosynthesis Pathway: Regulation and Function,” Genes 14 (2023): 933.

[36] X. Yang and K. Qian, “Protein O-GlcNAcylation: Emerging Mechanisms and Functions,” Nature Reviews Molecular Cell Biology 18 (2017): 452-465.

[37] A. R. Saltiel, “Insulin Signaling in Health and Disease,” Journal of Clinical Investigation 131 (2021): e142241.

[38] F. Giacco and M. Brownlee, “Oxidative Stress and Diabetic Complications,” Circulation Research 107 (2010): 1058-1070.

[39] S.-M. Huang, C.-S. Wu, M.-H. Chiu, H.-J. Yang, G.-S. Chen, and C.-C. E. Lan, “High-glucose Environment Induced Intracellular O-GlcNAc Glycosylation and Reduced Galectin-7 Expression in Keratinocytes: Implications on Impaired Diabetic Wound Healing,” Journal of Dermatological Science 87 (2017): 168-175.

[40] W. Sun, J. Xu, S. Li, et al., “GLUT1-mediated HMGB1 O-GlcNAcylation Drives Hyperglycemia-Induced Neutrophil Extracellular Trap Networks Formation via TLR4 Signaling and Exacerbates Fibroblast Inflammation,” Scientific Reports 15 (2025): 18853.

[41] N. J. Pedowitz, A. R. Batt, N. Darabedian, and M. R. Pratt, “MYPT1 O-GlcNAc Modification Regulates Sphingosine-1-phosphate Mediated Contraction,” Nature Chemical Biology 17 (2021): 169-177.

[42] K. Runager, M. Bektas, P. Berkowitz, and D. S. Rubenstein, “Targeting O-glycosyltransferase (OGT) to Promote Healing of Diabetic Skin Wounds,” Journal of Biological Chemistry 289 (2014): 5462-5466.

[43] M. Khalid, G. Petroianu, and A. Adem, “Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives,” Biomolecules 12 (2022): 542.

[44] A. Twarda-Clapa, A. Olczak, A. M. Białkowska, and M. Koziołkiewicz, “Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs,” Cells 11 (2022): 1312.

[45] C. Ott, K. Jacobs, E. Haucke, A. Navarrete Santos, T. Grune, and A. Simm, “Role of Advanced Glycation End Products in Cellular Signaling,” Redox Biology 2 (2014): 411-429.

[46] S.-I. Yamagishi and T. Matsui, “Role of Ligands of Receptor for Advanced Glycation End Products (RAGE) in Peripheral Artery Disease,” Rejuvenation Research 21 (2018): 456-463.

[47] H. Liao, J. Zakhaleva, and W. Chen, “Cells and Tissue Interactions With Glycated Collagen and Their Relevance to Delayed Diabetic Wound Healing,” Biomaterials 30 (2009): 1689-1696.

[48] D. Nolfi-Donegan, A. Braganza, and S. Shiva, “Mitochondrial Electron Transport Chain: Oxidative Phosphorylation, Oxidant Production, and Methods of Measurement,” Redox Biology 37 (2020): 101674.

[49] S. Rovira-Llopis, C. Bañuls, N. Diaz-Morales, A. Hernandez-Mijares, M. Rocha, and V. M. Victor, “Mitochondrial Dynamics in Type 2 Diabetes: Pathophysiological Implications,” Redox Biology 11 (2017): 637-645.

[50] W. Yan, C. Xie, S. Sun, et al., “SUCLG1 restricts POLRMT Succinylation to Enhance Mitochondrial Biogenesis and Leukemia Progression,” The EMBO Journal 43 (2024): 2337-2367.

[51] H. Zhang, Z. Yan, J. Zhu, et al., “Extracellular Mitochondrial-Derived Vesicles Affect the Progression of Diabetic Foot Ulcer by Regulating Oxidative Stress and Mitochondrial Dysfunction,” Advanced Science 12 (2025): e2407574.

[52] M. Wang, D. Yang, L. Li, et al., “A Dual Role of Mesenchymal Stem Cell Derived Small Extracellular Vesicles on TRPC6 Protein and Mitochondria to Promote Diabetic Wound Healing,” ACS Nano 18 (2024): 4871-4885.

[53] R. Z. Zhao, S. Jiang, L. Zhang, and Z. B. Yu, “Mitochondrial Electron Transport Chain, ROS Generation and Uncoupling (Review),” International Journal of Molecular Medicine 44 (2019): 3-15.

[54] S. J. Forrester, D. S. Kikuchi, M. S. Hernandes, Q. Xu, and K. K. Griendling, “Reactive Oxygen Species in Metabolic and Inflammatory Signaling,” Circulation Research 122 (2018): 877-902.

[55] Z. Zhen, J. Ren, and J. Zhu, “The Redox Requirement and Regulation During Cell Proliferation,” Trends in Endocrinology & Metabolism 35 (2024): 385-399.

[56] L. Sun, X. Wang, J. Saredy, Z. Yuan, X. Yang, and H. Wang, “Innate-adaptive Immunity Interplay and Redox Regulation in Immune Response,” Redox Biology 37 (2020): 101759.

[57] G. Bastianello, G. Porcella, G. V. Beznoussenko, et al., “Cell Stretching Activates an ATM Mechano-transduction Pathway That Remodels Cytoskeleton and Chromatin,” Cell Reports 42 (2023): 113555.

[58] D. Zheng, J. Liu, H. Piao, Z. Zhu, R. Wei, and K. Liu, “ROS-triggered Endothelial Cell Death Mechanisms: Focus on Pyroptosis, Parthanatos, and Ferroptosis,” Frontiers in Immunology 13 (2022): 1039241.

[59] B. Vergès, “Dyslipidemia in Type 1 Diabetes: A Masked Danger,” Trends in Endocrinology & Metabolism 31 (2020): 422-434.

[60] E. Bahiru, R. Hsiao, D. Phillipson, and K. E. Watson, “Mechanisms and Treatment of Dyslipidemia in Diabetes,” Current Cardiology Reports 23 (2021): 26.

[61] I. J. Neeland, S. Lim, A. Tchernof, et al., “Metabolic Syndrome,” Nature Reviews Disease Primers 10 (2024): 77.

[62] M. Koenen, M. A. Hill, P. Cohen, and J. R. Sowers, “Obesity, Adipose Tissue and Vascular Dysfunction,” Circulation Research 128 (2021): 951-968.

[63] A. C. Carpentier, D. P. Blondin, F. Haman, and D. Richard, “Brown Adipose Tissue—A Translational Perspective,” Endocrine Reviews 44 (2023): 143-192.

[64] L. Cheng, J. Wang, H. Dai, et al., “Brown and Beige Adipose Tissue: A Novel Therapeutic Strategy for Obesity and Type 2 Diabetes Mellitus,” Adipocyte 10 (2021): 48-65.

[65] S. C. Dyall, L. Balas, N. G. Bazan, et al., “Polyunsaturated Fatty Acids and Fatty Acid-derived Lipid Mediators: Recent Advances in the Understanding of Their Biosynthesis, Structures, and Functions,” Progress in Lipid Research 86 (2022): 101165.

[66] C. Jiménez-Sánchez, L. Oberhauser, and P. Maechler, “Role of Fatty Acids in the Pathogenesis of Ss-cell Failure and Type-2 Diabetes,” Atherosclerosis 398 (2024): 118623.

[67] A. Więckowska-Gacek, A. Mietelska-Porowska, M. Wydrych, and U. Wojda, “Western Diet as a Trigger of Alzheimer's Disease: From Metabolic Syndrome and Systemic Inflammation to Neuroinflammation and Neurodegeneration,” Ageing Research Reviews 70 (2021): 101397.

[68] E. Brennan, P. Kantharidis, M. E. Cooper, and C. Godson, “Pro-resolving Lipid Mediators: Regulators of Inflammation, Metabolism and Kidney Function,” Nature Reviews Nephrology 17 (2021): 725-739.

[69] N. Chiang, M. Sakuma, A. R. Rodriguez, B. W. Spur, D. Irimia, and C. N. Serhan, “Resolvin T-series Reduce Neutrophil Extracellular Traps,” Blood 139 (2022): 1222-1233.

[70] K. McDermott, M. Fang, A. J. M. Boulton, E. Selvin, and C. W. Hicks, “Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers,” Diabetes Care 46 (2023): 209-221.

[71] R. R. Yotsu, N. M. Pham, M. Oe, et al., “Comparison of Characteristics and Healing Course of Diabetic Foot Ulcers by Etiological Classification: Neuropathic, Ischemic, and Neuro-ischemic Type,” Journal of Diabetes and Its Complications 28 (2014): 528-535.

[72] D. O. Soyoye, O. O. Abiodun, R. T. Ikem, B. A. Kolawole, and A. O. Akintomide, “Diabetes and Peripheral Artery Disease: A Review,” World Journal of Diabetes 12 (2021): 827-838.

[73] A. Janus, E. Szahidewicz-Krupska, G. Mazur, and A. Doroszko, “Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders,” Mediators of Inflammation 2016 (2016): 1-10.

[74] D. Sun, S. Chen, S. Li, et al., “Enhancement of Glycolysis-dependent DNA Repair Regulated by FOXO1 Knockdown via PFKFB3 Attenuates Hyperglycemia-induced Endothelial Oxidative Stress Injury,” Redox Biology 59 (2023): 102589.

[75] D. R. Yang, M. Y. Wang, C. L. Zhang, and Y. Wang, “Endothelial Dysfunction in Vascular Complications of Diabetes: A Comprehensive Review of Mechanisms and Implications,” Frontiers in Endocrinology 15 (2024): 1359255.

[76] S. Bongarzone, V. Savickas, F. Luzi, and A. D. Gee, “Targeting the Receptor for Advanced Glycation Endproducts (RAGE): A Medicinal Chemistry Perspective,” Journal of Medicinal Chemistry 60 (2017): 7213-7232.

[77] P. Hou, J. Fang, Z. Liu, et al., “Macrophage Polarization and Metabolism in Atherosclerosis,” Cell Death & Disease 14 (2023): 691.

[78] K. Yahagi, F. D. Kolodgie, C. Lutter, et al., “Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus,” Arteriosclerosis, Thrombosis, and Vascular Biology 37 (2017): 191-204.

[79] M. S. Conte, A. W. Bradbury, P. Kolh, et al., “Global Vascular Guidelines on the Management of Chronic Limb-threatening Ischemia,” Journal of Vascular Surgery 69 (2019): 3S-125S.e40.

[80] T. Suga, T. Iso, T. Shimizu, et al., “Activation of Receptor for Advanced Glycation End Products Induces Osteogenic Differentiation of Vascular Smooth Muscle Cells,” Journal of Atherosclerosis and Thrombosis 18 (2011): 670-683.

[81] S. A. Steitz, M. Y. Speer, G. Curinga, et al., “Smooth Muscle Cell Phenotypic Transition Associated with Calcification,” Circulation Research 89 (2001): 1147-1154.

[82] T. Tanikawa, Y. Okada, R. Tanikawa, and Y. Tanaka, “Advanced Glycation End Products Induce Calcification of Vascular Smooth Muscle Cells Through RAGE/p38 MAPK,” Journal of Vascular Research 46 (2009): 572-580.

[83] Y. Hu, E. Chan, S. X. Wang, and B. Li, “Activation of p38 Mitogen-activated Protein Kinase Is Required for Osteoblast Differentiation,” Endocrinology 144 (2003): 2068-2074.

[84] A. M. Kay, C. L. Simpson, and J. A. Stewart, “The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification,” Journal of Diabetes Research 2016 (2016): 1-8.

[85] M. A. Hofmann Bowman, J. Gawdzik, U. Bukhari, et al., “S100A12 in Vascular Smooth Muscle Accelerates Vascular Calcification in Apolipoprotein E-Null Mice by Activating an Osteogenic Gene Regulatory Program,” Arteriosclerosis, Thrombosis, and Vascular Biology 31 (2011): 337-344.

[86] G. Zhao, M.-J. Xu, M.-M. Zhao, et al., “Activation of Nuclear Factor-kappa B Accelerates Vascular Calcification by Inhibiting Ankylosis Protein Homolog Expression,” Kidney International 82 (2012): 34-44.

[87] R. Villa-Bellosta, “Vascular Calcification: Key Roles of Phosphate and Pyrophosphate,” International Journal of Molecular Sciences 22 (2021): 13536.

[88] J. Bai, X. Ding, X. Du, X. Zhao, Z. Wang, and Z. Ma, “Diabetes Is Associated With Increased Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis,” Thrombosis Research 135 (2015): 90-95.

[89] N. Panchagnula and W. P. Brasher, “Hyperglycemia and Venous Thromboembolism,” Diagnostics 14 (2024): 1994.

[90] R. Njeim, W. S. Azar, A. H. Fares, S. T. Azar, H. Kfoury Kassouf, and A. A. Eid, “NETosis Contributes to the Pathogenesis of Diabetes and Its Complications,” Journal of Molecular Endocrinology 65 (2020): R65-R76.

[91] C. M. de Bont, W. C. Boelens, and G. J. M. Pruijn, “NETosis, Complement, and Coagulation: A Triangular Relationship,” Cellular & Molecular Immunology 16 (2019): 19-27.

[92] R. Kaur, M. Kaur, and J. Singh, “Endothelial Dysfunction and Platelet Hyperactivity in Type 2 Diabetes Mellitus: Molecular Insights and Therapeutic Strategies,” Cardiovascular Diabetology 17 (2018): 121.

[93] W. B. Horton and E. J. Barrett, “Microvascular Dysfunction in Diabetes Mellitus and Cardiometabolic Disease,” Endocrine Reviews 42 (2020): 29-55.

[94] Y. Shi and P. M. Vanhoutte, “Macro- and Microvascular Endothelial Dysfunction in Diabetes,” Journal of Diabetes 9 (2017): 434-449.

[95] X. T. Cheng, N. Huang, and Z. H. Sheng, “Programming Axonal Mitochondrial Maintenance and Bioenergetics in Neurodegeneration and Regeneration,” Neuron 110 (2022): 1899-1923.

[96] M. K. Jha, X. H. Ament, F. Yang, et al., “Reducing Monocarboxylate Transporter MCT1 Worsens Experimental Diabetic Peripheral Neuropathy,” Experimental Neurology 333 (2020): 113415.

[97] M. K. Jha, Y. Lee, K. A. Russell, et al., “Monocarboxylate Transporter 1 in Schwann Cells Contributes to Maintenance of Sensory Nerve Myelination During Aging,” Glia 68 (2020): 161-177.

[98] F. Bouçanova, G. Pollmeier, K. Sandor, et al., “Disrupted Function of Lactate Transporter MCT1, but Not MCT4, in Schwann Cells Affects the Maintenance of Motor End-plate Innervation,” Glia 69 (2021): 124-136.

[99] E. Babetto, K. M. Wong, and B. Beirowski, “A Glycolytic Shift in Schwann Cells Supports Injured Axons,” Nature Neuroscience 23 (2020): 1215-1228.

[100] L. Jia, M. Liao, A. Mou, et al., “Rheb-regulated Mitochondrial Pyruvate Metabolism of Schwann Cells Linked to Axon Stability,” Developmental Cell 56 (2021): 2980-2994.e6.

[101] S. Shanmughapriya, D. Langford, and K. Natarajaseenivasan, “Inter and Intracellular Mitochondrial Trafficking in Health and Disease,” Ageing Research Reviews 62 (2020): 101128.

[102] G. Pekkurnaz, J. C. Trinidad, X. Wang, D. Kong, and T. L. Schwarz, “Glucose Regulates Mitochondrial Motility via Milton Modification by <Em>O</Em>-GlcNAc Transferase,” Cell 158 (2014): 54-68.

[103] H. Maalmi, A. Strom, A. Petrera, et al., “Serum Neurofilament Light Chain: A Novel Biomarker for Early Diabetic Sensorimotor Polyneuropathy,” Diabetologia 66 (2023): 579-589.

[104] S. S. Devarakonda, S. Basha, A. Pithakumar, et al., “Molecular Mechanisms of Neurofilament Alterations and Its Application in Assessing Neurodegenerative Disorders,” Ageing Research Reviews 102 (2024): 102566.

[105] S. A. Eid, A. E. Rumora, B. Beirowski, et al., “New Perspectives in Diabetic Neuropathy,” Neuron 111 (2023): 2623-2641.

[106] A. E. Rumora, K. Guo, L. M. Hinder, et al., “A High-Fat Diet Disrupts Nerve Lipids and Mitochondrial Function in Murine Models of Neuropathy,” Frontiers in Physiology 13 (2022): 921942.

[107] J.-U. Park, B. Oh, J. P. Lee, M.-H. Choi, M.-J. Lee, and B.-S. Kim, “Influence of Microbiota on Diabetic Foot Wound in Comparison With Adjacent Normal Skin Based on the Clinical Features,” BioMed Research International 2019 (2019): 1-10.

[108] S. H. Han, J. S. Lee, K.-H. Song, Y. B. Choe, K. J. Ahn, and Y. W. Lee, “Differences in Foot Skin Microbiomes Between Patients With Type 2 Diabetes and Healthy Individuals,” Mycoses 63 (2020): 314-322.

[109] X.-N. Zhang, C.-Y. Wu, Z.-W. Wu, L.-X. Xu, F.-T. Jiang, and H.-W. Chen, “Association between the Diabetic Foot Ulcer and the Bacterial Colony of the Skin Based on 16S rRNA Gene Sequencing: An Observational Study,” Clinical, Cosmetic and Investigational Dermatology 16 (2023): 2801-2812.

[110] S. Zhang, S. Li, J. Huang, et al., “Gram-Negative Bacteria and Lipopolysaccharides as Risk Factors for the Occurrence of Diabetic Foot,” The Journal of Clinical Endocrinology & Metabolism 108 (2023): 2604-2614.

[111] Z. Versey, W. S. Da Cruz Nizer, E. Russell, et al., “Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation,” Frontiers in Immunology 12 (2021): 648554.

[112] K. K. Dwivedi, P. Lakhani, P. Sihota, K. Tikoo, S. Kumar, and N. Kumar, “The Multiscale Characterization and Constitutive Modeling of Healthy and Type 2 Diabetes Mellitus Sprague Dawley Rat Skin,” Acta Biomaterialia 158 (2023): 324-346.

[113] V. R. Moraes, M. O. Melo, and P. Maia Campos, “Evaluation of Morphological and Structural Skin Alterations on Diabetic Subjects by Biophysical and Imaging Techniques,” Life (Basel) 13 (2023): 579.

[114] H. I. El-Sayyad, S. A. Khalifa, Y. A. Fouda, and A. S. Yonis, “Effects of Diabetes and/or Hypercholesterolemia on Skin Development of Rat Fetuses,” Nutrition (Burbank, Los Angeles County, Calif) 28 (2012): 698-706.

[115] T. P. Prado, J. Morari, and E. P. Araújo, “Molecular and Morphological Alterations in Uninjured Skin of Streptozotocin-Induced Diabetic Mice,” Brazilian Journal of Medical and Biological Research 56 (2023): e12212.

[116] C. Pirri, C. Fede, N. Pirri, et al., “Diabetic Foot: The Role of Fasciae, a Narrative Review,” Biology (Basel) 10 (2021): 759.

[117] D. Correa-Gallegos, D. Jiang, S. Christ, et al., “Patch Repair of Deep Wounds by Mobilized Fascia,” Nature 576 (2019): 287-292.

[118] D. G. Menter, S. Kopetz, E. Hawk, et al., “Platelet “First Responders” in Wound Response, Cancer, and Metastasis,” Cancer and Metastasis Reviews 36 (2017): 199-213.

[119] E. M. Golebiewska and A. W. Poole, “Platelet Secretion: From Haemostasis to Wound Healing and Beyond,” Blood Reviews 29 (2015): 153-162.

[120] A. Zarbock, R. K. Polanowska-Grabowska, and K. Ley, “Platelet-neutrophil-interactions: Linking Hemostasis and Inflammation,” Blood Reviews 21 (2007): 99-111.

[121] F. W. Lam, A. R. Burns, C. W. Smith, and R. E. Rumbaut, “Platelets Enhance Neutrophil Transendothelial Migration via P-selectin Glycoprotein Ligand-1,” American Journal of Physiology-Heart and Circulatory Physiology 300 (2011): H468-H475.

[122] D. Scully, P. Sfyri, H. N. Wilkinson, et al., “Optimising Platelet Secretomes to Deliver Robust Tissue-Specific Regeneration,” Journal of Tissue Engineering and Regenerative Medicine 14 (2020): 82-98.

[123] C. Deppermann and P. Kubes, “Platelets and Infection,” Seminars in Immunology 28 (2016): 536-545.

[124] A. Shariati, A. Moradabadi, E. Ghaznavi-Rad, M. Dadmanesh, M. Komijani, and F. Nojoomi, “Investigation Into Antibacterial and Wound Healing Properties of Platelets Lysate Against Acinetobacter baumannii and Klebsiella pneumoniae Burn Wound Infections,” Annals of Clinical Microbiology and Antimicrobials 20 (2021): 40.

[125] Y. Xu, R. Geng, X. Meng, et al., “RETRACTED: The Impact of Inflammatory Biomarkers on Amputation Rates in Patients With Diabetic Foot Ulcers,” International Wound Journal 21 (2024): e14827.

[126] F. Asadian, F. Khani, A. Derakhshesh, and M. A. Takhshid, “Comparison of Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and C-reactive Protein in Predicting Osteomyelitis in Patients With Diabetic Foot Ulcer,” Journal of Diabetes & Metabolic Disorders 23 (2024): 647-654.

[127] K. Zhang, S. Ding, X. Lyu, Q. Tan, and Z. Wang, “Correlation Between the Platelet-to-Lymphocyte Ratio and Diabetic Foot Ulcer in Patients With Type 2 Diabetes Mellitus,” Journal of Clinical Laboratory Analysis 35 (2021): e23719.

[128] W. Chen, K. Chen, Z. Xu, et al., “Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Predict Mortality in Patients With Diabetic Foot Ulcers Undergoing Amputations,” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 14 (2021): 821-829.

[129] M. A. Eren, A. E. Gunes, I. Kirhan, and T. Sabuncu, “The Role of the Platelet-to-lymphocyte Ratio and Neutrophil-to-lymphocyte Ratio in the Prediction of Length and Cost of Hospital Stay in Patients With Infected Diabetic Foot Ulcers: A Retrospective Comparative Study,” Acta Orthopaedica Et Traumatologica Turcica 54 (2020): 127-131.

[130] X. Yang, T. Yan, D. Shen, et al., “Prognostic Value of Wagner Grade and Platelet Level in Diabetics With Infected Foot Ulcers after Antibiotic Therapy,” Infection and Drug Resistance 16 (2023): 7435-7445.

[131] K. Yammine, G. Abou Orm, J. Mouawad, and C. Assi, “Basic Haematological Tests as Inflammatory Performance Markers of Patients Treated either by Conservative Surgery or minor Amputation for Infected Diabetic Foot Ulcers,” Wound Repair and Regeneration 31 (2023): 627-634.

[132] Z. Qian, H. Wang, Y. Bai, et al., “Improving Chronic Diabetic Wound Healing Through an Injectable and Self-Healing Hydrogel With Platelet-Rich Plasma Release,” ACS Applied Materials & Interfaces 12 (2020): 55659-55674.

[133] H. Ouyang, Y. Tang, F. Yang, et al., “Platelet-rich Plasma for the Treatment of Diabetic Foot Ulcer: A Systematic Review,” Frontiers in Endocrinology 14 (2023): 1256081.

[134] B. M. Bakadia, A. A. Qaed Ahmed, L. Lamboni, et al., “Engineering Homologous Platelet-rich Plasma, Platelet-rich Plasma-derived Exosomes, and Mesenchymal Stem Cell-derived Exosomes-based Dual-crosslinked Hydrogels as Bioactive Diabetic Wound Dressings,” Bioact Mater 28 (2023): 74-94.

[135] M. Phillipson and P. Kubes, “The Healing Power of Neutrophils,” Trends in Immunology 40 (2019): 635-647.

[136] S. de Oliveira, E. E. Rosowski, and A. Huttenlocher, “Neutrophil Migration in Infection and Wound Repair: Going Forward in Reverse,” Nature Reviews Immunology 16 (2016): 378-391.

[137] P. Niethammer, C. Grabher, A. T. Look, and T. J. Mitchison, “A Tissue-scale Gradient of Hydrogen Peroxide Mediates Rapid Wound Detection in Zebrafish,” Nature 459 (2009): 996-999.

[138] K. Pittman and P. Kubes, “Damage-associated Molecular Patterns Control Neutrophil Recruitment,” Journal of Innate Immunity 5 (2013): 315-323.

[139] T. Lämmermann, P. V. Afonso, B. R. Angermann, et al., “Neutrophil Swarms Require LTB4 and Integrins at Sites of Cell Death in Vivo,” Nature 498 (2013): 371-375.

[140] H. M. Isles, C. A. Loynes, S. Alasmari, et al., “Pioneer Neutrophils Release Chromatin Within in Vivo Swarms,” Elife 10 (2021): e68755.

[141] V. Mutua and L. J. Gershwin, “A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics,” Clinical Reviews in Allergy & Immunology 61 (2021): 194-211.

[142] V. Papayannopoulos, “Neutrophil Extracellular Traps in Immunity and Disease,” Nature Reviews Immunology 18 (2018): 134-147.

[143] D. Jiang, J. Muschhammer, Y. Qi, et al., “Suppression of Neutrophil-Mediated Tissue Damage—A Novel Skill of Mesenchymal Stem Cells,” Stem Cells 34 (2016): 2393-2406.

[144] K. Kienle, K. M. Glaser, S. Eickhoff, et al., “Neutrophils Self-limit Swarming to Contain Bacterial Growth in Vivo,” Science 372 (2021): eabe7729.

[145] C. Farrera and B. Fadeel, “Macrophage Clearance of Neutrophil Extracellular Traps Is a Silent Process,” The Journal of Immunology 191 (2013): 2647-2656.

[146] A. Fischer, J. Wannemacher, S. Christ, et al., “Neutrophils Direct Preexisting Matrix to Initiate Repair in Damaged Tissues,” Nature Immunology 23 (2022): 518-531.

[147] A. P. Sawaya, R. C. Stone, S. R. Brooks, et al., “Deregulated Immune Cell Recruitment Orchestrated by FOXM1 Impairs human Diabetic Wound Healing,” Nature Communications 11 (2020): 4678.

[148] R. Roy, J. Zayas, S. K. Singh, et al., “Overriding Impaired FPR Chemotaxis Signaling in Diabetic Neutrophil Stimulates Infection Control in Murine Diabetic Wound,” Elife 11 (2022): e72071.

[149] R. Roy, F. Mahmud, J. Zayas, T. M. Kuzel, J. Reiser, and S. H. Shafikhani, “Reduced Bioactive Microbial Products (Pathogen-Associated Molecular Patterns) Contribute to Dysregulated Immune Responses and Impaired Healing in Infected Wounds in Mice With Diabetes,” Journal of Investigative Dermatology 144 (2024): 387-397.e11.

[150] G. P. Fadini, L. Menegazzo, M. Rigato, et al., “NETosis Delays Diabetic Wound Healing in Mice and Humans,” Diabetes 65 (2016): 1061-1071.

[151] S. Yang, Y. Feng, L. Chen, et al., “Disulfiram Accelerates Diabetic Foot Ulcer Healing by Blocking NET Formation via Suppressing the NLRP3/Caspase-1/GSDMD Pathway,” Translational Research 254 (2023): 115-127.

[152] S. Yang, S. Wang, L. Chen, et al., “Neutrophil Extracellular Traps Delay Diabetic Wound Healing by Inducing Endothelial-to-Mesenchymal Transition via the Hippo Pathway,” International Journal of Biological Sciences 19 (2023): 347-361.

[153] Y. S. Lee, S. U. Kang, M.-H. Lee, et al., “GnRH Impairs Diabetic Wound Healing Through Enhanced NETosis,” Cellular & Molecular Immunology 17 (2020): 856-864.

[154] D. Liu, P. Yang, M. Gao, et al., “NLRP3 activation Induced by Neutrophil Extracellular Traps Sustains Inflammatory Response in the Diabetic Wound,” Clinical Science 133 (2019): 565-582.

[155] W. Huang, J. Jiao, J. Liu, et al., “MFG-E8 Accelerates Wound Healing in Diabetes by Regulating “NLRP3 Inflammasome-neutrophil Extracellular Traps” Axis,” Cell Death Discovery 6 (2020): 84.

[156] J. V. Dovi, L. K. He, and L. A. DiPietro, “Accelerated Wound Closure in Neutrophil-depleted Mice,” Journal of Leukocyte Biology 73 (2003): 448-455.

[157] M. Locati, G. Curtale, and A. Mantovani, “Diversity, Mechanisms, and Significance of Macrophage Plasticity,” Annual Review of Pathology: Mechanisms of Disease 15 (2020): 123-147.

[158] G. Theocharidis, B. E. Thomas, D. Sarkar, et al., “Single Cell Transcriptomic Landscape of Diabetic Foot Ulcers,” Nature Communications 13 (2022): 181.

[159] N. Jetten, N. Roumans, M. J. Gijbels, et al., “Wound Administration of M2-polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses,” PLoS ONE 9 (2014): e102994.

[160] D. Dreymueller, B. Denecke, A. Ludwig, and W. Jahnen-Dechent, “Embryonic Stem Cell-derived M2 -Like Macrophages Delay Cutaneous Wound Healing,” Wound Repair and Regeneration 21 (2013): 44-54.

[161] M. J. Crane, J. M. Daley, O. Van Houtte, S. K. Brancato, W. L. Henry, and J. E. Albina, “The Monocyte to Macrophage Transition in the Murine Sterile Wound,” PLoS ONE 9 (2014): e86660.

[162] R. M. Kratofil, P. Kubes, and J. F. Deniset, “Monocyte Conversion during Inflammation and Injury,” Arteriosclerosis, Thrombosis, and Vascular Biology 37 (2017): 35-42.

[163] A. E. Louiselle, S. M. Niemiec, C. Zgheib, and K. W. Liechty, “Macrophage Polarization and Diabetic Wound Healing,” Translational Research 236 (2021): 109-116.

[164] A. C. Doran, A. Yurdagul, and I. Tabas, “Efferocytosis in Health and Disease,” Nature Reviews Immunology 20 (2020): 254-267.

[165] P. Mehrotra and K. S. Ravichandran, “Drugging the Efferocytosis Process: Concepts and Opportunities,” Nature Reviews Drug Discovery 21 (2022): 601-620.

[166] E. Boada-Romero, J. Martinez, B. L. Heckmann, and D. R. Green, “The Clearance of Dead Cells by Efferocytosis,” Nature Reviews Molecular Cell Biology 21 (2020): 398-414.

[167] B. D. Gerlach, P. B. Ampomah, A. Yurdagul, et al., “Efferocytosis Induces Macrophage Proliferation to Help Resolve Tissue Injury,” Cell Metabolism 33 (2021): 2445-2463.e8.

[168] M. Viaud, S. Ivanov, N. Vujic, et al., “Lysosomal Cholesterol Hydrolysis Couples Efferocytosis to Anti-Inflammatory Oxysterol Production,” Circulation Research 122 (2018): 1369-1384.

[169] A. Das, S. Ghatak, M. Sinha, et al., “Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes,” The Journal of Immunology 196 (2016): 5089-5100.

[170] Z. Yao, W. Qi, H. Zhang, et al., “Down-regulated GAS6 Impairs Synovial Macrophage Efferocytosis and Promotes Obesity-associated Osteoarthritis,” Elife 12 (2023): e83069.

[171] X. Wang, Q. He, C. Zhou, et al., “Prolonged Hypernutrition Impairs TREM2-dependent Efferocytosis to License Chronic Liver Inflammation and NASH Development,” Immunity 56 (2023): 58-77.e11.

[172] I. Florance and S. Ramasubbu, “Current Understanding on the Role of Lipids in Macrophages and Associated Diseases,” International Journal of Molecular Sciences 24 (2022): 589.

[173] D. Lv, X. Cao, L. Zhong, et al., “Targeting Phenylpyruvate Restrains Excessive NLRP3 Inflammasome Activation and Pathological Inflammation in Diabetic Wound Healing,” Cell Reports Medicine 4 (2023): 101129.

[174] T. Karasawa, A. Kawashima, F. Usui-Kawanishi, et al., “Saturated Fatty Acids Undergo Intracellular Crystallization and Activate the NLRP3 Inflammasome in Macrophages,” Arteriosclerosis, Thrombosis, and Vascular Biology 38 (2018): 744-756.

[175] N. C. Wilcox, G. Taheri, K. Halievski, S. Talbot, J. R. Silva, and N. Ghasemlou, “Interactions Between Skin-resident Dendritic and Langerhans Cells and Pain-sensing Neurons,” Journal of Allergy and Clinical Immunology 154 (2024): 11-19.

[176] F.-S. X. Yu, P. S. Y. Lee, L. Yang, et al., “The Impact of Sensory Neuropathy and Inflammation on Epithelial Wound Healing in Diabetic Corneas,” Progress in Retinal and Eye Research 89 (2022): 101039.

[177] N. Gao, C. Yan, P. Lee, H. Sun, and F. S. Yu, “Dendritic Cell Dysfunction and Diabetic Sensory Neuropathy in the Cornea,” Journal of Clinical Investigation 126 (2016): 1998-2011.

[178] S. Maschalidi, P. Mehrotra, B. N. Keçeli, et al., “Targeting SLC7A11 Improves Efferocytosis by Dendritic Cells and Wound Healing in Diabetes,” Nature 606 (2022): 776-784.

[179] A. W. Ho and T. S. Kupper, “T Cells and the Skin: From Protective Immunity to Inflammatory Skin Disorders,” Nature Reviews Immunology 19 (2019): 490-502.

[180] F. O. Nestle, P. Di Meglio, J.-Z. Qin, and B. J. Nickoloff, “Skin Immune Sentinels in Health and Disease,” Nature Reviews Immunology 9 (2009): 679-691.

[181] J. M. Jameson, G. Cauvi, L. L. Sharp, D. A. Witherden, and W. L. Havran, “γδ T Cell-induced Hyaluronan Production by Epithelial Cells Regulates Inflammation,” The Journal of Experimental Medicine 201 (2005): 1269-1279.

[182] L. L. Sharp, J. M. Jameson, G. Cauvi, and W. L. Havran, “Dendritic Epidermal T Cells Regulate Skin Homeostasis Through Local Production of Insulin-Like Growth Factor 1,” Nature Immunology 6 (2005): 73-79.

[183] K. R. Taylor, R. E. Mills, A. E. Costanzo, and J. M. Jameson, “γδ T Cells Are Reduced and Rendered Unresponsive by Hyperglycemia and Chronic TNFα in Mouse Models of Obesity and Metabolic Disease,” PLoS ONE 5 (2010): e11422.

[184] A. Nosbaum, N. Prevel, H.-A. Truong, et al., “Cutting Edge: Regulatory T Cells Facilitate Cutaneous Wound Healing,” The Journal of Immunology 196 (2016): 2010-2014.

[185] A. N. Mathur, B. Zirak, I. C. Boothby, et al., “Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation during Skin-Barrier Repair,” Immunity 50 (2019): 655-667.e4.

[186] Y. Li, Y. Wang, L. Zhou, et al., “Vγ4 T Cells Inhibit the Pro-healing Functions of Dendritic Epidermal T Cells to Delay Skin Wound Closure through IL-17A,” Frontiers in Immunology 9 (2018): 240.

[187] P. J. Finley, C. E. DeClue, S. A. Sell, J. M. DeBartolo, and L. P. Shornick, “Diabetic Wounds Exhibit Decreased Ym1 and Arginase Expression With Increased Expression of IL-17 and IL-20,” Advances in Wound Care 5 (2016): 486-494.

[188] J. Lee, M. P. Rodero, J. Patel, D. Moi, R. Mazzieri, and K. Khosrotehrani, “Interleukin-23 Regulates Interleukin-17 Expression in Wounds, and Its Inhibition Accelerates Diabetic Wound Healing Through the Alteration of Macrophage Polarization,” The FASEB Journal 32 (2018): 2086-2094.

[189] K. Mukai, M. Tsai, H. Saito, and S. J. Galli, “Mast Cells as Sources of Cytokines, Chemokines, and Growth Factors,” Immunological Reviews 282 (2018): 121-150.

[190] N. Strbo, N. Yin, and O. Stojadinovic, “Innate and Adaptive Immune Responses in Wound Epithelialization,” Advances in Wound Care 3 (2014): 492-501.

[191] M. L. Mangoni, A. M. McDermott, and M. Zasloff, “Antimicrobial Peptides and Wound Healing: Biological and Therapeutic Considerations,” Experimental Dermatology 25 (2016): 167-173.

[192] J. D. Heilborn, M. F. Nilsson, O. Sørensen, et al., “The Cathelicidin Anti-microbial Peptide LL-37 Is Involved in Re-epithelialization of human Skin Wounds and Is Lacking in Chronic Ulcer Epithelium,” Journal of Investigative Dermatology 120 (2003): 379-389.

[193] B. Rivas-Santiago, V. Trujillo, A. Montoya, et al., “Expression of Antimicrobial Peptides in Diabetic Foot Ulcer,” Journal of Dermatological Science 65 (2012): 19-26.

[194] E. Miranda, K. Bramono, E. Yunir, et al., “Efficacy of LL-37 Cream in Enhancing Healing of Diabetic Foot Ulcer: A Randomized Double-blind Controlled Trial,” Archives of Dermatological Research 315 (2023): 2623-2633.

[195] S. De Oliveira, A. López-Muñoz, S. Candel, P. Pelegrín, Â. Calado, and V. Mulero, “ATP Modulates Acute Inflammation in Vivo Through Dual Oxidase 1-Derived H2O2 Production and NF-κB Activation,” The Journal of Immunology 192 (2014): 5710-5719.

[196] W. Razzell, I. R. Evans, P. Martin, and W. Wood, “Calcium Flashes Orchestrate the Wound Inflammatory Response Through DUOX Activation and Hydrogen Peroxide Release,” Current Biology 23 (2013): 424-429.

[197] A. E. K. Loo, R. Ho, and B. Halliwell, “Mechanism of Hydrogen Peroxide-induced Keratinocyte Migration in a Scratch-wound Model,” Free Radical Biology and Medicine 51 (2011): 884-892.

[198] E. J. Calabrese, G. Dhawan, R. Kapoor, E. Agathokleous, and V. Calabrese, “Hormesis: Wound Healing and Keratinocytes,” Pharmacological Research 183 (2022): 106393.

[199] Y. Wang and D. T. Graves, “Keratinocyte Function in Normal and Diabetic Wounds and Modulation by FOXO1,” Journal of Diabetes Research 2020 (2020): 1-9.

[200] H. E. Talbott, S. Mascharak, M. Griffin, D. C. Wan, and M. T. Longaker, “Wound Healing, Fibroblast Heterogeneity, and Fibrosis,” Cell Stem Cell 29 (2022): 1161-1180.

[201] C. Ganier, E. Rognoni, G. Goss, M. Lynch, and F. M. Watt, “Fibroblast Heterogeneity in Healthy and Wounded Skin,” Cold Spring Harbor Perspectives in Biology 14 (2022): a041238.

[202] D. Jiang, D. Correa-Gallegos, S. Christ, et al., “Two Succeeding Fibroblastic Lineages Drive Dermal Development and the Transition From Regeneration to Scarring,” Nature Cell Biology 20 (2018): 422-431.

[203] Y. Rinkevich, G. G. Walmsley, M. S. Hu, et al., “Identification and Isolation of a Dermal Lineage With Intrinsic Fibrogenic Potential,” Science 348 (2015): aaa2151.

[204] M. R. Haas, D. V. Nguyen, and B. A. Shook, “Recovery of Altered Diabetic Myofibroblast Heterogeneity and Gene Expression Are Associated With CD301b+ Macrophages,” Biomedicines 9 (2021): 1752.

[205] Y. Liu, Y. Liu, W. He, et al., “Fibroblasts: Immunomodulatory Factors in Refractory Diabetic Wound Healing,” Frontiers in Immunology 13 (2022): 918223.

[206] P. Pakshir, N. Noskovicova, M. Lodyga, et al., “The Myofibroblast at a Glance,” Journal of Cell Science 133 (2020): jcs227900.

[207] J. Massagué and D. Sheppard, “TGF-β Signaling in Health and Disease,” Cell 186 (2023): 4007-4037.

[208] Y. E. Zhang, “Non-Smad Signaling Pathways of the TGF-β Family,” Cold Spring Harbor Perspectives in Biology 9 (2017): a022129.

[209] T. A. M. Andrade, D. S. Masson-Meyers, G. F. Caetano, et al., “Skin Changes in Streptozotocin-induced Diabetic Rats,” Biochemical and Biophysical Research Communications 490 (2017): 1154-1161.

[210] L. L. Silveira, M. M. Sarandy, R. D. Novaes, M. Morais-Santos, and R. V. Gonçalves, “OxInflammation Affects Transdifferentiation to Myofibroblasts, Prolonging Wound Healing in Diabetes: A Systematic Review,” International Journal of Molecular Sciences 25 (2024): 8992.

[211] F. Gong, Y. Zhang, S. Cheng, et al., “Inhibition of TGFβ1/Smad Pathway by NF-κB Induces Inflammation Leading to Poor Wound Healing in High Glucose,” Cells & Development 172 (2022): 203814.

[212] S. Li, X. Ding, H. Zhang, Y. Ding, and Q. Tan, “IL-25 Improves Diabetic Wound Healing Through Stimulating M2 Macrophage Polarization and Fibroblast Activation,” International Immunopharmacology 106 (2022): 108605.

[213] Y.-T. Lin, J.-S. Chen, M.-H. Wu, et al., “Galectin-1 Accelerates Wound Healing by Regulating the Neuropilin-1/Smad3/NOX4 Pathway and ROS Production in Myofibroblasts,” Journal of Investigative Dermatology 135 (2015): 258-268.

[214] R. N. Gomes, F. Manuel, and D. S. Nascimento, “The Bright Side of Fibroblasts: Molecular Signature and Regenerative Cues in Major Organs,” Npj Regenerative Medicine 6 (2021): 43.

[215] R. Datta, T. Bansal, S. Rana, et al., “Myocyte-Derived Hsp90 Modulates Collagen Upregulation via Biphasic Activation of STAT-3 in Fibroblasts During Cardiac Hypertrophy,” Molecular and Cellular Biology 37 (2017): e00611-e00616.

[216] Y. Zhang, J.-H. Wang, Y.-Y. Zhang, et al., “Deletion of Interleukin-6 Alleviated Interstitial Fibrosis in Streptozotocin-induced Diabetic Cardiomyopathy of Mice Through Affecting TGFβ1 and miR-29 Pathways,” Scientific Reports 6 (2016): 23010.

[217] T. Nishikai-Yan Shen, S. Kanazawa, M. Kado, et al., “Interleukin-6 Stimulates Akt and p38 MAPK Phosphorylation and Fibroblast Migration in Non-diabetic but Not Diabetic Mice,” PLoS ONE 12 (2017): e0178232.

[218] D. Duscher, Z. N. Maan, A. J. Whittam, et al., “Fibroblast-Specific Deletion of Hypoxia Inducible Factor-1 Critically Impairs Murine Cutaneous Neovascularization and Wound Healing,” Plastic and Reconstructive Surgery 136 (2015): 1004-1013.

[219] Z. Ma, R. Mo, P. Yang, et al., “PDK4 facilitates Fibroblast Functions and Diabetic Wound Healing Through Regulation of HIF-1α Protein Stability and Gene Expression,” The FASEB Journal 37 (2023): e23215.

[220] V. G. Sunkari, F. Lind, I. R. Botusan, et al., “Hyperbaric Oxygen Therapy Activates Hypoxia-Inducible Factor 1 ( HIF -1), Which Contributes to Improved Wound Healing in Diabetic Mice,” Wound Repair and Regeneration 23 (2015): 98-103.

[221] D. Correa-Gallegos, H. Ye, B. Dasgupta, et al., “CD201+ fascia Progenitors Choreograph Injury Repair,” Nature 623 (2023): 792-802.

[222] I. R. Botusan, V. G. Sunkari, O. Savu, et al., “Stabilization of HIF-1α Is Critical to Improve Wound Healing in Diabetic Mice,” Proceedings of the National Academy of Sciences of the United States of America 105 (2008): 19426-19431.

[223] S.-B. Catrina, K. Okamoto, T. Pereira, K. Brismar, and L. Poellinger, “Hyperglycemia Regulates Hypoxia-Inducible Factor-1α Protein Stability and Function,” Diabetes 53 (2004): 3226-3232.

[224] X. Huang, P. Liang, B. Jiang, et al., “Hyperbaric Oxygen Potentiates Diabetic Wound Healing by Promoting Fibroblast Cell Proliferation and Endothelial Cell Angiogenesis,” Life Sciences 259 (2020): 118246.

[225] X. Niu, Y. Chen, L. Qi, et al., “Hypoxia Regulates Angeogenic-osteogenic Coupling Process via Up-regulating IL-6 and IL-8 in human Osteoblastic Cells Through Hypoxia-inducible Factor-1α Pathway,” Cytokine 113 (2019): 117-127.

[226] K. Fu, X. Zheng, Y. Chen, et al., “Role of Matrix Metalloproteinases in Diabetic Foot Ulcers: Potential Therapeutic Targets,” Frontiers in Pharmacology 13 (2022): 1050630.

[227] M. Chang and T. T. Nguyen, “Strategy for Treatment of Infected Diabetic Foot Ulcers,” Accounts of Chemical Research 54 (2021): 1080-1093.

[228] W.-Q. Zhang, W. Tang, S.-Q. Hu, et al., “Effect of Matrix Metalloproteinases on the Healing of Diabetic Foot Ulcer: A Systematic Review,” Journal of Tissue Viability 32 (2023): 51-58.

[229] S. Patel, S. Srivastava, M. R. Singh, and D. Singh, “Mechanistic Insight Into Diabetic Wounds: Pathogenesis, Molecular Targets and Treatment Strategies to Pace Wound Healing,” Biomedicine & Pharmacotherapy 112 (2019): 108615.

[230] E. Rognoni, A. O. Pisco, T. Hiratsuka, et al., “Fibroblast state Switching Orchestrates Dermal Maturation and Wound Healing,” Molecular Systems Biology 14 (2018): e8174.

[231] S. Mascharak, H. E. Desjardins-Park, M. F. Davitt, et al., “Preventing Engrailed-1 Activation in Fibroblasts Yields Wound Regeneration Without Scarring,” Science 372 (2021): eaba2374.

[232] J. Yu, S. Choi, J. Um, and K. S. Park, “Reduced Expression of YAP in Dermal Fibroblasts Is Associated With Impaired Wound Healing in Type 2 Diabetic Mice,” Tissue Engineering and Regenerative Medicine 14 (2017): 49-55.

[233] F. S. Younesi, A. E. Miller, T. H. Barker, F. M. V. Rossi, and B. Hinz, “Fibroblast and Myofibroblast Activation in Normal Tissue Repair and Fibrosis,” Nature Reviews Molecular Cell Biology 25 (2024): 617-638.

[234] M. O. Yu Lin, D. Sampath, D. A. Bosykh, et al., “YAP/TAZ Drive Agrin-Matrix Metalloproteinase 12-Mediated Diabetic Skin Wound Healing,” Journal of Investigative Dermatology 145 (2025): 155-170.

[235] X.-T. Xie, C.-H. Gao, L.-F. Tan, et al., “Gene-engineered Polypeptide Hydrogels With on-demand Oxygenation and ECM-cell Interaction Mimicry for Diabetic Wound Healing,” Biomaterials 316 (2025): 122984.

[236] Z. Li, J. Huang, Y. Jiang, et al., “Novel Temperature-Sensitive Hydrogel Promotes Wound Healing through YAP and MEK-Mediated Mechanosensitivity,” Advanced Healthcare Materials 11 (2022): 2201878.

[237] J. H. Lee, E.-J. Kim, D.-K. Kim, et al., “Hypoxia Induces PDK4 Gene Expression Through Induction of the Orphan Nuclear Receptor ERRγ,” PLoS ONE 7 (2012): e46324.

[238] W. Q. Ma, X. J. Sun, Y. Zhu, and N. F. Liu, “PDK4 promotes Vascular Calcification by Interfering With Autophagic Activity and Metabolic Reprogramming,” Cell Death & Disease 11 (2020): 991.

[239] Z. Ma, Y. Ding, X. Ding, H. Mou, R. Mo, and Q. Tan, “PDK4 rescues High-glucose-induced Senescent Fibroblasts and Promotes Diabetic Wound Healing Through Enhancing Glycolysis and Regulating YAP and JNK Pathway,” Cell Death Discovery 9 (2023): 424.

[240] N. A. R. Ring, H. Dworak, B. Bachmann, et al., “The p-rpS6-zone Delineates Wounding Responses and the Healing Process,” Developmental Cell 58 (2023): 981-992.e6.

[241] M. Tanaka, T. Morifuji, M. Yoshikawa, R. Nakanishi, and H. Fujino, “Effects of Combined Treatment With Blood Flow Restriction and Low-Intensity Electrical Stimulation on Diabetes Mellitus-Associated Muscle Atrophy in Rats,” Journal of Diabetes 11 (2019): 326-334.

[242] D. T. Loughlin and C. M. Artlett, “Modification of Collagen by 3-Deoxyglucosone Alters Wound Healing Through Differential Regulation of p38 MAP Kinase,” PLoS ONE 6 (2011): e18676.

[243] M. Wolak, J. Drobnik, and E. Bojanowska, “Exendin-4 Differentially Modulates Essential Functions of human Dermal Fibroblasts Under Normoglycemic and Hyperglycemic Conditions,” Journal of Physiology and Pharmacology 72 (2021).

[244] D. B. Gurevich, C. E. Severn, C. Twomey, et al., “Live Imaging of Wound Angiogenesis Reveals Macrophage Orchestrated Vessel Sprouting and Regression,” The EMBO Journal 37 (2018): e97786.

[245] E. R. Michalczyk, L. Chen, D. Fine, et al., “Pigment Epithelium-Derived Factor (PEDF) as a Regulator of Wound Angiogenesis,” Scientific Reports 8 (2018): 11142.

[246] X. Zhu, C. Qiu, Y. Wang, et al., “FGFR1 SUMOylation Coordinates Endothelial Angiogenic Signaling in Angiogenesis,” Proceedings of the National Academy of Sciences of the United States of America 119 (2022): e2202631119.

[247] C. M. Minutti, R. V. Modak, F. Macdonald, et al., “A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation,” Immunity 50 (2019): 645-654.e646.

[248] R. Gao, P. Zhou, Y. Li, and Q. Li, “High Glucose-induced IL-7/IL-7R Upregulation of Dermal Fibroblasts Inhibits Angiogenesis in a Paracrine Way in Delayed Diabetic Wound Healing,” Journal of Cell Communication and Signaling 17 (2023): 1023-1038.

[249] G. Eelen, P. de Zeeuw, M. Simons, and P. Carmeliet, “Endothelial Cell Metabolism in Normal and Diseased Vasculature,” Circulation Research 116 (2015): 1231-1244.

[250] H.-H. Chen, F.-S. Fu, Q.-W. Chen, Y. Zhang, and X.-Z. Zhang, “Two-Pronged Microbe Delivery of Nitric Oxide and Oxygen for Diabetic Wound Healing,” Nano Letters 23 (2023): 5595-5602.

[251] A. Franz, W. Wood, and P. Martin, “Fat Body Cells Are Motile and Actively Migrate to Wounds to Drive Repair and Prevent Infection,” Developmental Cell 44 (2018): 460-470.e3.

[252] L.-J. Zhang, C. F. Guerrero-Juarez, T. Hata, et al., “Dermal Adipocytes Protect Against Invasive Staphylococcus aureus Skin Infection,” Science 347 (2015): 67-71.

[253] S. Kalgudde Gopal, R. Dai, A. M. Stefanska, et al., “Wound Infiltrating Adipocytes Are Not Myofibroblasts,” Nature Communications 14 (2023): 3020.

[254] B. A. Shook, R. R. Wasko, O. Mano, et al., “Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair,” Cell Stem Cell 26 (2020): 880-895.e6.

[255] W. A. Vieira, H. Sadie-Van Gijsen, and W. F. Ferris, “Free Fatty Acid G-protein Coupled Receptor Signaling in M1 Skewed White Adipose Tissue Macrophages,” Cellular and Molecular Life Sciences 73 (2016): 3665-3676.

[256] C. O. Souza, A. A. Teixeira, L. A. Biondo, L. S. Silveira, P. C. Calder, and J. C. Rosa Neto, “Palmitoleic Acid Reduces the Inflammation in LPS -Stimulated Macrophages by Inhibition of NF κB, Independently of PPAR s,” Clinical and Experimental Pharmacology and Physiology 44 (2017): 566-575.

[257] P. O. Cooper, S. S. Kleb, S. K. Noonepalle, et al., “G-protein-coupled Receptor 84 Regulates Acute Inflammation in Normal and Diabetic Skin Wounds,” Cell Reports 43 (2024): 114288.

[258] B. A. Schmidt and V. Horsley, “Intradermal Adipocytes Mediate Fibroblast Recruitment During Skin Wound Healing,” Development (Cambridge, England) 140 (2013): 1517-1527.

[259] J. Cai, Y. Quan, S. Zhu, et al., “The Browning and Mobilization of Subcutaneous White Adipose Tissue Supports Efficient Skin Repair,” Cell Metabolism 36 (2024): 1287-1301.e7.

[260] M. V. Plikus, C. F. Guerrero-Juarez, M. Ito, et al., “Regeneration of Fat Cells From Myofibroblasts During Wound Healing,” Science 355 (2017): 748-752.

[261] T. Fujiwara, T. Kubo, S. Kanazawa, et al., “Direct Contact of Fibroblasts With Neuronal Processes Promotes Differentiation to Myofibroblasts and Induces Contraction of Collagen Matrix in Vitro,” Wound Repair and Regeneration 21 (2013): 588-594.

[262] V. Parfejevs, J. Debbache, O. Shakhova, et al., “Injury-activated Glial Cells Promote Wound Healing of the Adult Skin in Mice,” Nature Communications 9 (2018): 236.

[263] S. Huang, P. Kuri, Y. Aubert, et al., “Lgr6 marks Epidermal Stem Cells With a Nerve-dependent Role in Wound Re-epithelialization,” Cell Stem Cell 28 (2021): 1582-1596.e6.

[264] S. Beggs, D. Alvares, A. Moss, et al., “A Role for NT-3 in the Hyperinnervation of Neonatally Wounded Skin,” Pain 153 (2012): 2133-2139.

[265] D. Jiang, H. G. Machens, and Y. Rinkevich, “Sensory Neurons: Unveiling the Symphony of Wound Healing,” Signal Transduction and Targeted Therapy 9 (2024): 177.

[266] Y.-Z. Lu, B. Nayer, S. K. Singh, et al., “CGRP Sensory Neurons Promote Tissue Healing via Neutrophils and Macrophages,” Nature 628 (2024): 604-611.

[267] S. Yang, L. Hu, R. Han, and Y. Yang, “Neuropeptides, Inflammation, Biofilms, and Diabetic Foot Ulcers,” Experimental and Clinical Endocrinology & Diabetes 130 (2022): 439-446.

[268] K. Yin, T. Qiao, Y. Zhang, et al., “Unraveling Shared Risk Factors for Diabetic Foot Ulcer: A Comprehensive Mendelian Randomization Analysis,” BMJ Open Diabetes Research & Care 11 (2023): e003523.

[269] S. Klein, A. Gastaldelli, H. Yki-Järvinen, and P. E. Scherer, “Why Does Obesity Cause Diabetes?,” Cell Metabolism 34 (2022): 11-20.

[270] M. Kleinert, C. Clemmensen, S. M. Hofmann, et al., “Animal Models of Obesity and Diabetes Mellitus,” Nature Reviews Endocrinology 14 (2018): 140-162.

[271] S. A. Cruz, Y. C. Tseng, H. Kaiya, and P. P. Hwang, “Ghrelin Affects Carbohydrate-glycogen Metabolism via Insulin Inhibition and Glucagon Stimulation in the Zebrafish (Danio rerio) Brain,” Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 156 (2010): 190-200.

[272] M. Gorissen, N. J. Bernier, S. B. Nabuurs, G. Flik, and M. O. Huising, “Two Divergent Leptin Paralogues in Zebrafish (Danio rerio) That Originate Early in Teleostean Evolution,” Journal of Endocrinology 201 (2009): 329-339.

[273] Y. Wang, M. Rovira, S. Yusuff, and M. J. Parsons, “Genetic Inducible Fate Mapping in Larval Zebrafish Reveals Origins of Adult Insulin-producing β-cells,” Development (Cambridge, England) 138 (2011): 609-617.

[274] A. S. Olsen, M. P. Sarras, and R. V. Intine, “Limb Regeneration Is Impaired in an Adult Zebrafish Model of Diabetes Mellitus,” Wound Repair and Regeneration 18 (2010): 532-542.

[275] B. Lin, J. Ma, Y. Fang, et al., “Advances in Zebrafish for Diabetes Mellitus With Wound Model,” Bioengineering 10 (2023): 330.

[276] R. Richardson, K. Slanchev, C. Kraus, P. Knyphausen, S. Eming, and M. Hammerschmidt, “Adult Zebrafish as a Model System for Cutaneous Wound-Healing Research,” Journal of Investigative Dermatology 133 (2013): 1655-1665.

[277] R. Naomi, H. Bahari, M. D. Yazid, H. Embong, and F. Othman, “Zebrafish as a Model System to Study the Mechanism of Cutaneous Wound Healing and Drug Discovery: Advantages and Challenges,” Pharmaceuticals 14 (2021): 1058.

[278] R. V. Intine, A. S. Olsen, and P. M. Sarras, “A Zebrafish Model of Diabetes Mellitus and Metabolic Memory,” Journal of Visualized Experiments: JoVE 72 (2013): e50232.

[279] K.-H. Cho, J.-H. Kim, H.-S. Nam, and D.-J. Kang, “Efficacy Comparison Study of Human Epidermal Growth Factor (EGF) Between Heberprot-P® and Easyef® in Adult Zebrafish and Embryo Under Presence or Absence Combination of Diabetic Condition and Hyperlipidemia to Mimic Elderly Patients,” Geriatrics 7 (2022): 45.

[280] I. Wibowo, N. Utami, T. Anggraeni, et al., “Propolis Can Improve Caudal Fin Regeneration in Zebrafish (Danio rerio) Induced by the Combined Administration of Alloxan and Glucose,” Zebrafish 18 (2021): 274-281.

[281] S. Morris, P. M. Cholan, W. J. Britton, and S. H. Oehlers, “Glucose Inhibits Haemostasis and Accelerates Diet-induced Hyperlipidaemia in Zebrafish Larvae,” Scientific Reports 11 (2021): 19049.

[282] A. Heydemann, “An Overview of Murine High Fat Diet as a Model for Type 2 Diabetes Mellitus,” Journal of Diabetes Research 2016 (2016): 1-14.

[283] T. A. Lutz, “Mammalian Models of Diabetes Mellitus, With a Focus on Type 2 Diabetes Mellitus,” Nature Reviews Endocrinology 19 (2023): 350-360.

[284] V. Rai, R. Moellmer, and D. K. Agrawal, “Clinically Relevant Experimental Rodent Models of Diabetic Foot Ulcer,” Molecular and Cellular Biochemistry 477 (2022): 1239-1247.

[285] B. K. R. Sanapalli, V. Yele, M. K. Singh, P. Thaggikuppe Krishnamurthy, and V. V. S. R. Karri, “Preclinical Models of Diabetic Wound Healing: A Critical Review,” Biomedicine & Pharmacotherapy 142 (2021): 111946.

[286] N. Naldaiz-Gastesi, O. A. Bahri, A. López De Munain, K. J. A. Mccullagh, and A. Izeta, “The Panniculus Carnosus Muscle: An Evolutionary Enigma at the Intersection of Distinct Research Fields,” Journal of Anatomy 233 (2018): 275-288.

[287] A. Summerfield, F. Meurens, and M. E. Ricklin, “The Immunology of the Porcine Skin and Its Value as a Model for human Skin,” Molecular Immunology 66 (2015): 14-21.

[288] T. P. Sullivan, W. H. Eaglstein, S. C. Davis, and P. Mertz, “The Pig as a Model for human Wound Healing,” Wound Repair and Regeneration 9 (2001): 66-76.

[289] S. Renner, C. Braun-Reichhart, A. Blutke, et al., “Permanent Neonatal Diabetes in INS C94Y Transgenic Pigs,” Diabetes 62 (2013): 1505-1511.

[290] K. Umeyama, M. Watanabe, H. Saito, et al., “Dominant-negative Mutant Hepatocyte Nuclear Factor 1α Induces Diabetes in Transgenic-cloned Pigs,” Transgenic Research 18 (2009): 697-706.

[291] S. Renner, C. Fehlings, N. Herbach, et al., “Glucose Intolerance and Reduced Proliferation of Pancreatic β-Cells in Transgenic Pigs with Impaired Glucose-Dependent Insulinotropic Polypeptide Function,” Diabetes 59 (2010): 1228-1238.

[292] S. E. Thomson, S. V. Mclennan, A. Hennessy, et al., “A Novel Primate Model of Delayed Wound Healing in Diabetes: Dysregulation of Connective Tissue Growth Factor,” Diabetologia 53 (2010): 572-583.

[293] S. Heffernan, A. Phippard, A. Sinclair, et al., “A Baboon ( Papio hamadryas ) Model of Insulin-Dependent Diabetes,” Journal of Medical Primatology 24 (1995): 29-34.

[294] C. O. Audu, W. J. Melvin, A. D. Joshi, et al., “Macrophage-specific Inhibition of the Histone Demethylase JMJD3 Decreases STING and Pathologic Inflammation in Diabetic Wound Repair,” Cellular & Molecular Immunology 19 (2022): 1251-1262.

[295] L. Song, X. Chang, L. Hu, et al., “Accelerating Wound Closure with Metrnl in Normal and Diabetic Mouse Skin,” Diabetes 72 (2023): 1692-1706.

[296] C. Y. Zhang and M. Yang, “Roles of Fibroblast Growth Factors in the Treatment of Diabetes,” World Journal of Diabetes 15 (2024): 392-402.

[297] D. M. Ornitz and N. Itoh, “The Fibroblast Growth Factor Signaling Pathway,” WIREs Developmental Biology 4 (2015): 215-266.

[298] Y. Liu, Y. Liu, J. Deng, W. Li, and X. Nie, “Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects,” Frontiers in Endocrinology 12 (2021): 744868.

[299] A. Y. W. Wong, N. M. F. Hooi, B. S. Y. Yeo, et al., “Improving Diabetic Wound-Healing Outcomes with Topical Growth Factor Therapies,” The Journal of Clinical Endocrinology & Metabolism 109 (2024): e1642-e1651.

[300] Y. Hao, W. Zhao, H. Zhang, W. Zheng, and Q. Zhou, “Carboxymethyl Chitosan-based Hydrogels Containing Fibroblast Growth Factors for Triggering Diabetic Wound Healing,” Carbohydrate Polymers 287 (2022): 119336.

[301] Y. Xiong, L. Chen, P. Liu, et al., “All-in-One: Multifunctional Hydrogel Accelerates Oxidative Diabetic Wound Healing Through Timed-Release of Exosome and Fibroblast Growth Factor,” Small 18 (2022): e2104229.

[302] M.-Q. Tong, C.-T. Lu, L.-T. Huang, et al., “Polyphenol-driven Facile Assembly of a Nanosized Acid Fibroblast Growth Factor-containing Coacervate Accelerates the Healing of Diabetic Wounds,” Acta Biomaterialia 157 (2023): 467-486.

[303] Y. Zhang, F. Hei, Y. Xiao, et al., “Acidic Fibroblast Growth Factor Inhibits Reactive Oxygen Species-induced Epithelial-mesenchymal Transdifferentiation in Vascular Endothelial Cells via the miR-155-5p/SIRT1/Nrf2/HO-1 Pathway to Promote Wound Healing in Diabetic Mice,” Burns & Trauma 12 (2024): tkae010.

[304] F. Huang, T. Gao, Y. Feng, et al., “Bioinspired Collagen Scaffold Loaded With bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization,” ACS Applied Materials & Interfaces 16 (2024): 45989-46004.

[305] Z. Li, X. Qiu, G. Guan, et al., “The Role of FGF-21 in Promoting Diabetic Wound Healing by Modulating High Glucose-induced Inflammation,” Heliyon 10 (2024): e30022.

[306] S.-Y. Zheng, X.-X. Wan, P. A. Kambey, et al., “Therapeutic Role of Growth Factors in Treating Diabetic Wound,” World Journal of Diabetes 14 (2023): 364-395.

[307] F. S. Bang, V. Leeberg, M. Ding, and C. H. Dreyer, “The Effect of VEGF Stimulation in Diabetic Foot Ulcers: A Systematic Review,” Wound Repair and Regeneration 32 (2024): 384-392.

[308] F. Liu, X. Xu, and T. Sun, “Vascular Endothelial Growth Factor Accelerates Healing of Foot Ulcers in Diabetic Rats via Promoting M2 Macrophage Polarization,” Diabetic Medicine 41 (2024): e15388.

[309] J. Huang, R. Yang, J. Jiao, et al., “A Click Chemistry-mediated all-peptide Cell Printing Hydrogel Platform for Diabetic Wound Healing,” Nature Communications 14 (2023): 7856.

[310] J. Liu, Y. Zhang, C. Liu, et al., “A Single Dose of VEGF-A Circular RNA Sustains in Situ Long-term Expression of Protein to Accelerate Diabetic Wound Healing,” Journal of Controlled Release 373 (2024): 319-335.

[311] J. M. Smiell, T. J. Wieman, D. L. Steed, B. H. Perry, A. R. Sampson, and B. H. Schwab, “Efficacy and Safety of becaplermin (recombinant human platelet-derived growth factor-BB) in Patients With Nonhealing, Lower Extremity Diabetic Ulcers: A Combined Analysis of Four Randomized Studies,” Wound Repair and Regeneration 7 (1999): 335-346.

[312] D. J. Margolis, C. Bartus, O. Hoffstad, S. Malay, and J. A. Berlin, “Effectiveness of Recombinant human Platelet-Derived Growth Factor for the Treatment of Diabetic Neuropathic Foot Ulcers,” Wound Repair and Regeneration 13 (2005): 531-536.

[313] L. Tang, S. Cai, X. Lu, et al., “Platelet-Derived Growth Factor Nanocapsules With Tunable Controlled Release for Chronic Wound Healing,” Small 20 (2024): 2310743.

[314] S. Barrientos, H. Brem, O. Stojadinovic, and M. Tomic-Canic, “Clinical Application of Growth Factors and Cytokines in Wound Healing,” Wound Repair and Regeneration 22 (2014): 569-578.

[315] Y. K. Alshoubaki, Y.-Z. Lu, J. M. D. Legrand, et al., “A Superior Extracellular Matrix Binding Motif to Enhance the Regenerative Activity and Safety of Therapeutic Proteins,” Npj Regenerative Medicine 8 (2023): 25.

[316] D.-Y. Zhao, Y.-N. Su, Y.-H. Li, T.-Q. Yu, J. Li, and C.-Q. Tu, “Efficacy and Safety of Recombinant human Epidermal Growth Factor for Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis of Randomised Controlled Trials,” International Wound Journal 17 (2020): 1062-1073.

[317] E. Özker, “Intralesional Epidermal Growth Factor Therapy in Recalcitrant Diabetic Foot Ulcers,” Journal of Wound Care 32 (2023): S14-s21.

[318] D. Jiang and K. Scharffetter-Kochanek, “Mesenchymal Stem Cells Adaptively Respond to Environmental Cues Thereby Improving Granulation Tissue Formation and Wound Healing,” Frontiers in Cell and Developmental Biology 8 (2020): 697.

[319] L. Huelsboemer, L. Knoedler, A. Kochen, et al., “Cellular Therapeutics and Immunotherapies in Wound Healing—on the Pulse of Time?,” Military Medical Research 11 (2024): 23.

[320] R. Kalluri and V. S. LeBleu, “The Biology, Function, and Biomedical Applications of Exosomes,” Science 367 (2020).

[321] J. Y. Ding , M. J. Chen, L. F. Wu, et al., “Mesenchymal Stem Cell-derived Extracellular Vesicles in Skin Wound Healing: Roles, Opportunities and Challenges,” Military Medical Research 10 (2023): 36.

[322] D. Jiang, Y. Qi, N. G. Walker, et al., “The Effect of Adipose Tissue Derived MSCs Delivered by a Chemically Defined Carrier on Full-thickness Cutaneous Wound Healing,” Biomaterials 34 (2013): 2501-2515.

[323] D. Jiang, K. Singh, J. Muschhammer, et al., “MSCs Rescue Impaired Wound Healing in a Murine LAD1 Model by Adaptive Responses to Low TGF-β1 Levels,” EMBO Reports 21 (2020): e49115.

[324] Y. An, S. Lin, X. Tan, et al., “Exosomes From Adipose-Derived Stem Cells and Application to Skin Wound Healing,” Cell Proliferation 54 (2021): e12993.

[325] P. A. Shiekh, A. Singh, and A. Kumar, “Exosome Laden Oxygen Releasing Antioxidant and Antibacterial Cryogel Wound Dressing OxOBand Alleviate Diabetic and Infectious Wound Healing,” Biomaterials 249 (2020): 120020.

[326] T. Jiang, S. Liu, Z. Wu, et al., “ADSC-exo@MMP-PEG Smart Hydrogel Promotes Diabetic Wound Healing by Optimizing Cellular Functions and Relieving Oxidative Stress,” Materials Today Bio 16 (2022): 100365.

[327] Y. Song, Y. You, X. Xu, et al., “Adipose-Derived Mesenchymal Stem Cell-Derived Exosomes Biopotentiated Extracellular Matrix Hydrogels Accelerate Diabetic Wound Healing and Skin Regeneration,” Advanced Science 10 (2023): e2304023.

[328] Z. Wang, C. Feng, H. Liu, et al., “Hypoxic Pretreatment of Adipose-Derived Stem Cells Accelerates Diabetic Wound Healing via Circ-Gcap14 and HIF-1α/VEGF Mediated Angiopoiesis,” International Journal of Stem Cells 14 (2021): 447-454.

[329] N. Hu, Z. Cai, X. Jiang, et al., “Hypoxia-pretreated ADSC-derived Exosome-embedded Hydrogels Promote Angiogenesis and Accelerate Diabetic Wound Healing,” Acta Biomaterialia 157 (2023): 175-186.

[330] J. Wang, H. Wu, Y. Peng, et al., “Hypoxia Adipose Stem Cell-derived Exosomes Promote High-quality Healing of Diabetic Wound Involves Activation of PI3K/Akt Pathways,” Journal of Nanobiotechnology 19 (2021): 202.

[331] Y. Shi, S. Wang, W. Zhang, et al., “Bone Marrow Mesenchymal Stem Cells Facilitate Diabetic Wound Healing Through the Restoration of Epidermal Cell Autophagy via the HIF-1α/TGF-β1/SMAD Pathway,” Stem Cell Research & Therapy 13 (2022): 314.

[332] T. Tang, L. Chen, M. Zhang, et al., “Exosomes Derived From BMSCs Enhance Diabetic Wound Healing Through Circ-Snhg11 Delivery,” Diabetology & Metabolic Syndrome 16 (2024): 37.

[333] J. Chen, X. Li, H. Liu, et al., “Bone Marrow Stromal Cell-Derived Exosomal Circular RNA Improves Diabetic Foot Ulcer Wound Healing by Activating the Nuclear Factor Erythroid 2-Related Factor 2 Pathway and Inhibiting Ferroptosis,” Diabetic Medicine 40 (2023): e15031.

[334] X. Zhou, C. Ye, L. Jiang, et al., “The Bone Mesenchymal Stem Cell-derived Exosomal miR-146a-5p Promotes Diabetic Wound Healing in Mice via Macrophage M1/M2 Polarization,” Molecular and Cellular Endocrinology 579 (2024): 112089.

[335] Y. Shi, S. Wang, D. Liu, et al., “Exosomal miR-4645-5p From Hypoxic Bone Marrow Mesenchymal Stem Cells Facilitates Diabetic Wound Healing by Restoring Keratinocyte Autophagy,” Burns & Trauma 12 (2024): tkad058.

[336] Y. Hu, R. Tao, L. Chen, et al., “Exosomes Derived From Pioglitazone-pretreated MSCs Accelerate Diabetic Wound Healing Through Enhancing Angiogenesis,” Journal of Nanobiotechnology 19 (2021): 150.

[337] M. Yu, W. Liu, J. Li, et al., “Exosomes Derived From Atorvastatin-pretreated MSC Accelerate Diabetic Wound Repair by Enhancing Angiogenesis via AKT/eNOS Pathway,” Stem Cell Research & Therapy 11 (2020): 350.

[338] L. Wang, Y. Cai, Q. Zhang, and Y. Zhang, “Pharmaceutical Activation of Nrf2 Accelerates Diabetic Wound Healing by Exosomes From Bone Marrow Mesenchymal Stem Cells,” International Journal of Stem Cells 15 (2022): 164-172.

[339] W. Lu, X. Du, S. Zou, et al., “IFN -γ Enhances the Therapeutic Efficacy of MSCs -Derived Exosome via miR -126-3p in Diabetic Wound Healing by Targeting SPRED1,” Journal of Diabetes 16 (2024): e13465.

[340] C. Hou, L. Shen, Q. Huang, et al., “The Effect of Heme Oxygenase-1 Complexed With Collagen on MSC Performance in the Treatment of Diabetic Ischemic Ulcer,” Biomaterials 34 (2013): 112-120.

[341] J. Wu, Y. Feng, Y. Wang, et al., “MG53 binding to CAV3 Facilitates Activation of eNOS/NO Signaling Pathway to Enhance the Therapeutic Benefits of Bone Marrow-derived Mesenchymal Stem Cells in Diabetic Wound Healing,” International Immunopharmacology 136 (2024): 112410.

[342] N. Wang, X. Liu, Z. Tang, et al., “Increased BMSC Exosomal miR-140-3p Alleviates Bone Degradation and Promotes Bone Restoration by Targeting Plxnb1 in Diabetic Rats,” Journal of Nanobiotechnology 20 (2022): 97.

[343] L. Zheng, H. Song, Y. Li, H. Li, G. Lin, and Z. Cai, “Insulin-Induced Gene 1-Enhance Secretion of BMSC Exosome Enriched in miR-132-3p Promoting Wound Healing in Diabetic Mice,” Molecular Pharmaceutics 21 (2024): 4372-4385.

[344] C. Zhang, L. Huang, X. Wang, et al., “Topical and Intravenous Administration of human Umbilical Cord Mesenchymal Stem Cells in Patients With Diabetic Foot Ulcer and Peripheral Arterial Disease: A Phase I Pilot Study With a 3-year Follow-up,” Stem Cell Research & Therapy 13 (2022): 451.

[345] L. Teng, M. Maqsood, M. Zhu, et al., “Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Accelerate Diabetic Wound Healing via Promoting M2 Macrophage Polarization, Angiogenesis, and Collagen Deposition,” International Journal of Molecular Sciences 23 (2022): 10421.

[346] C. Yan, Y. Xv, Z. Lin, et al., “Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Accelerate Diabetic Wound Healing via Ameliorating Oxidative Stress and Promoting Angiogenesis,” Frontiers in Bioengineering and Biotechnology 10 (2022): 829868.

[347] Q. Wei, Y. Wang, K. Ma, et al., “Extracellular Vesicles From Human Umbilical Cord Mesenchymal Stem Cells Facilitate Diabetic Wound Healing through MiR-17-5p-mediated Enhancement of Angiogenesis,” Stem Cell Reviews and Reports 18 (2022): 1025-1040.

[348] Y. Zhang, P. Zhang, X. Gao, L. Chang, Z. Chen, and X. Mei, “Preparation of Exosomes Encapsulated Nanohydrogel for Accelerating Wound Healing of Diabetic Rats by Promoting Angiogenesis,” Materials Science and Engineering: C 120 (2021): 111671.

[349] L. Wang, J. Chen, J. Song, et al., “Activation of the Wnt/β-catenin Signalling Pathway Enhances Exosome Production by hucMSCs and Improves Their Capability to Promote Diabetic Wound Healing,” Journal of Nanobiotechnology 22 (2024): 373.

[350] R. Yang, S. Zhou, J. Huang, et al., “The Role of Q10 Engineering Mesenchymal Stem Cell-derived Exosomes in Inhibiting Ferroptosis for Diabetic Wound Healing,” Burns & Trauma 12 (2024): tkae054.

[351] J.-Y. Li, K.-K. Ren, W.-J. Zhang, et al., “Human Amniotic Mesenchymal Stem Cells and Their Paracrine Factors Promote Wound Healing by Inhibiting Heat Stress-induced Skin Cell Apoptosis and Enhancing Their Proliferation Through Activating PI3K/AKT Signaling Pathway,” Stem Cell Research & Therapy 10 (2019): 247.

[352] S. Fu, H. Zhang, X. Li, et al., “Exosomes Derived From Human Amniotic Mesenchymal Stem Cells Facilitate Diabetic Wound Healing by Angiogenesis and Enrich Multiple lncRNAs,” Tissue Engineering and Regenerative Medicine 20 (2023): 295-308.

[353] S. Vander Beken, J. C. Vries, B. Meier-Schiesser, et al., “Newly Defined ATP-Binding Cassette Subfamily B Member 5 Positive Dermal Mesenchymal Stem Cells Promote Healing of Chronic Iron-Overload Wounds via Secretion of Interleukin-1 Receptor Antagonist,” Stem Cells 37 (2019): 1057-1074.

[354] G. Lao, M. Ren, X. Wang, et al., “Human Tissue Inhibitor of Metalloproteinases-1 Improved Wound Healing in Diabetes Through Its Anti-Apoptotic Effect,” Experimental Dermatology 28 (2019): 528-535.

[355] T. T. Nguyen, D. Ding, W. R. Wolter, et al., “Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing,” Journal of Medicinal Chemistry 61 (2018): 8825-8837.

[356] Z. Li, C. Qian, X. Zheng, et al., “Collagen/Chitosan/Genipin Hydrogel Loaded With Phycocyanin Nanoparticles and ND-336 for Diabetic Wound Healing,” International Journal of Biological Macromolecules 266 (2024): 131220.

[357] J. Sonamuthu, Y. Cai, H. Liu, et al., “MMP-9 Responsive Dipeptide-tempted Natural Protein Hydrogel-based Wound Dressings for Accelerated Healing Action of Infected Diabetic Wound,” International Journal of Biological Macromolecules 153 (2020): 1058-1069.

[358] H.-C. Luo, K.-J. Mai, E. Liu, et al., “Efficiency and Safety of Dextran-PAMAM/siMMP-9 Complexes for Decreasing Matrix Metalloproteinase-9 Expression and Promoting Wound Healing in Diabetic Rats,” Bioconjugate Chemistry 33 (2022): 2398-2410.

[359] B. Lan, L. Zhang, L. Yang, et al., “Sustained Delivery of MMP-9 siRNA via Thermosensitive Hydrogel Accelerates Diabetic Wound Healing,” Journal of Nanobiotechnology 19 (2021): 130.

[360] Y. Li, W. Song, L. Kong, Y. He, and H. Li, “Injectable and Microporous Microgel-Fiber Granular Hydrogel Loaded With Bioglass and siRNA for Promoting Diabetic Wound Healing,” Small 20 (2024): e2309599.

[361] Y. Li, X. Zhang, D. He, Z. Ma, K. Xue, and H. Li, “45S5 Bioglass® Works Synergistically With siRNA to Downregulate the Expression of Matrix Metalloproteinase-9 in Diabetic Wounds,” Acta Biomaterialia 145 (2022): 372-389.

[362] J.-W. Wang, Y.-Z. Zhu, X. Hu, et al., “Extracellular Vesicles Derived From Adipose-Derived Stem Cells Accelerate Diabetic Wound Healing by Suppressing the Expression of Matrix Metalloproteinase-9,” Current Pharmaceutical Biotechnology 23 (2022): 894-901.

[363] J. Li, Y. Wu, Q. Yuan, et al., “Gelatin Microspheres Based on H8-Loaded Macrophage Membrane Vesicles to Promote Wound Healing in Diabetic Mice,” ACS Biomaterials Science & Engineering 10 (2024): 2251-2269.

[364] N. Li, A. Zhan, Y. Jiang, and H. Liu, “A Novel Matrix Metalloproteinases-cleavable Hydrogel Loading Deferoxamine Accelerates Diabetic Wound Healing,” International Journal of Biological Macromolecules 222 (2022): 1551-1559.

[365] P. Deng, Z. Shi, F. Fang, et al., “Wireless Matrix Metalloproteinase-9 Sensing by Smart Wound Dressing With Controlled Antibacterial Nanoparticles Release Toward Chronic Wound Management,” Biosensors and Bioelectronics 268 (2025): 116860.

[366] H. Aksoy, Ö. Çevik, A. Şen, F. Göğer, T. Şekerler, and A. Şener, “Effect of Horse-chestnut Seed Extract on Matrix Metalloproteinase-1 and -9 During Diabetic Wound Healing,” Journal of Food Biochemistry 43 (2019): e12758.

[367] R. Zhou, C. Xiang, G. Cao, et al., “Berberine Accelerated Wound Healing by Restoring TrxR1/JNK in Diabetes,” Clinical Science 135 (2021): 613-627.

[368] N. López-López, I. González-Curiel, M. B. Treviño-Santa Cruz, et al., “Expression and Vitamin D-mediated Regulation of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs) in Healthy Skin and in Diabetic Foot Ulcers,” Archives of Dermatological Research 306 (2014): 809-821.

[369] L. Li, D. Chen, C. Wang, G. Liu, and X. Ran, “The Effect of Autologous Platelet-Rich Gel on the Dynamic Changes of the Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-2 Expression in the Diabetic Chronic Refractory Cutaneous Ulcers,” Journal of Diabetes Research 2015 (2015): 1-6.

[370] J. W. Burrow, J. A. Koch, H.-H. Chuang, W. Zhong, D. D. Dean, and V. L. Sylvia, “Nitric Oxide Donors Selectively Reduce the Expression of Matrix Metalloproteinases-8 and -9 by human Diabetic Skin Fibroblasts,” Journal of Surgical Research 140 (2007): 90-98.

[371] T. T. Nguyen, J. I. Jones, W. R. Wolter, et al., “Hyperbaric Oxygen Therapy Accelerates Wound Healing in Diabetic Mice by Decreasing Active Matrix Metalloproteinase-9,” Wound Repair and Regeneration 28 (2020): 194-201.

[372] E. K. White, A. Uberoi, J. T.-C. Pan, et al., “Alcaligenes Faecaliscorrects Aberrant Matrix Metalloproteinase Expression to Promote Reepithelialization of Diabetic Wounds,” Science Advances 10 (2024): eadj2020.

[373] A. Kita, S. Yamamoto, Y. Saito, and T. S. Chikenji, “Cellular Senescence and Wound Healing in Aged and Diabetic Skin,” Frontiers in Physiology 15 (2024): 1344116.

[374] K. Y. Fung, C. Louis, R. D. Metcalfe, et al., “Emerging Roles for IL-11 in Inflammatory Diseases,” Cytokine 149 (2022): 155750.

[375] L. S. C. Lok, O. Monteiro, and D. T. Baptista-Hon, “Unlocking Longevity: How Blocking IL-11 Signaling Could Extend Healthspan and Lifespan,” MedComm—Future Medicine 3 (2024): e101.

[376] Z. Piperigkou, M. Götte, A. D. Theocharis, and N. K. Karamanos, “Insights Into the Key Roles of Epigenetics in Matrix Macromolecules-associated Wound Healing,” Advanced Drug Delivery Reviews 129 (2018): 16-36.

[377] C. Ling and T. Rönn, “Epigenetics in Human Obesity and Type 2 Diabetes,” Cell Metabolism 29 (2019): 1028-1044.

[378] J. Zhao, S. Yang, B. Shu, et al., “Transient High Glucose Causes Persistent Vascular Dysfunction and Delayed Wound Healing by the DNMT1-Mediated Ang-1/NF-κB Pathway,” Journal of Investigative Dermatology 141 (2021): 1573-1584.

[379] K. Harithpriya, K. Ganesan, and K. M. Ramkumar, “Pterostilbene Reverses Epigenetic Silencing of Nrf2 and Enhances Antioxidant Response in Endothelial Cells in Hyperglycemic Microenvironment,” Nutrients 16 (2024): 2045.

[380] K. Singh, D. Pal, M. Sinha, et al., “Epigenetic Modification of MicroRNA-200b Contributes to Diabetic Vasculopathy,” Molecular Therapy 25 (2017): 2689-2704.

[381] Q. Tan, W. Wang, C. Yang, et al., “α-Ketoglutarate Is Associated With Delayed Wound Healing in Diabetes,” Clinical Endocrinology 85 (2016): 54-61.

[382] L. Zhou, M. Ren, T. Zeng, et al., “TET2-interacting Long Noncoding RNA Promotes Active DNA Demethylation of the MMP-9 Promoter in Diabetic Wound Healing,” Cell Death & Disease 10 (2019): 813.

[383] L. Zhou, W. Wang, C. Yang, et al., “GADD45a Promotes Active DNA Demethylation of the MMP-9 Promoter via Base Excision Repair Pathway in AGEs-Treated Keratinocytes and in Diabetic Male Rat Skin,” Endocrinology 159 (2018): 1172-1186.

[384] F. M. Davis, A. Dendekker, A. Kimball, et al., “Epigenetic Regulation of TLR4 in Diabetic Macrophages Modulates Immunometabolism and Wound Repair,” The Journal of Immunology 204 (2020): 2503-2513.

[385] A. S. Kimball, A. Joshi, W. F. Carson, et al., “The Histone Methyltransferase MLL1 Directs Macrophage-Mediated Inflammation in Wound Healing and Is Altered in a Murine Model of Obesity and Type 2 Diabetes,” Diabetes 66 (2017): 2459-2471.

[386] F. M. Davis, A. Dendekker, A. D. Joshi, et al., “Palmitate-TLR4 Signaling Regulates the Histone Demethylase, JMJD3, in Macrophages and Impairs Diabetic Wound Healing,” European Journal of Immunology 50 (2020): 1929-1940.

[387] A. S. Kimball, F. M. Davis, A. Dendekker, et al., “The Histone Methyltransferase Setdb2 Modulates Macrophage Phenotype and Uric Acid Production in Diabetic Wound Repair,” Immunity 51 (2019): 258-271.e5.

[388] A. D. Dendekker, F. M. Davis, A. D. Joshi, et al., “TNF-α Regulates Diabetic Macrophage Function Through the Histone Acetyltransferase MOF,” JCI Insight 5 (2020): e132306.

[389] R. Teena, U. Dhamodharan, D. Ali, K. Rajesh, and K. M. Ramkumar, “Gene Expression Profiling of Multiple Histone Deacetylases (HDAC) and Its Correlation With NRF2-Mediated Redox Regulation in the Pathogenesis of Diabetic Foot Ulcers,” Biomolecules 10 (2020): 1466.

[390] K. Karnam, K. Sedmaki, P. Sharma, A. Mahale, B. Ghosh, and O. P. Kulkarni, “Pharmacological Blockade of HDAC3 Accelerates Diabetic Wound Healing by Regulating Macrophage Activation,” Life Sciences 321 (2023): 121574.

[391] J. Gao, Y. Wang, W. Li, et al., “Loss of Histone Deacetylase 2 Inhibits Oxidative Stress Induced by High Glucose via the HO-1/SIRT1 Pathway in Endothelial Progenitor Cells,” Gene 678 (2018): 1-7.

[392] K. Karnam, K. Sedmaki, P. Sharma, et al., “HDAC6 inhibitor Accelerates Wound Healing by Inhibiting Tubulin Mediated IL-1β Secretion in Diabetic Mice,” Biochimica Et Biophysica Acta (BBA)—Molecular Basis of Disease 1866 (2020): 165903.

[393] Y. Xue, C. Chen, R. Tan, et al., “Artificial Intelligence-Assisted Bioinformatics, Microneedle, and Diabetic Wound Healing: A “New Deal” of an Old Drug,” ACS Applied Materials & Interfaces 14 (2022): 37396-37409.

[394] T. Wang, X. Li, Y. Tao, X. Wang, L. Li, and J. Liu, “METTL3-mediated NDUFB5 m6A Modification Promotes Cell Migration and Mitochondrial Respiration to Promote the Wound Healing of Diabetic Foot Ulcer,” Journal of Translational Medicine 22 (2024): 643.

[395] J. Zhang, F. Chen, W. Wei, et al., “Nr-CWS Regulates METTL3-mediated m6A Modification of CDS2 mRNA in Vascular Endothelial Cells and Has Prognostic Significance,” Communications Biology 7 (2024): 1348.

[396] J. Zhou, T. Wei, and Z. He, “ADSCs Enhance VEGFR3-mediated Lymphangiogenesis via METTL3-mediated VEGF-C m6A Modification to Improve Wound Healing of Diabetic Foot Ulcers,” Molecular Medicine 27 (2021): 146.

[397] D. Liang, W.-J. Lin, M. Ren, et al., “m6A reader YTHDC1 Modulates Autophagy by Targeting SQSTM1 in Diabetic Skin,” Autophagy 18 (2022): 1318-1337.

[398] J. Wang, R. Zhu, Y. Dong, et al., “YTHDF3 suppresses Declines in Corneal Epithelial Wound Healing Through Upregulating the Wnt/β-catenin Signaling Pathway and THBS2 Expression in Diabetic Corneas,” International Journal of Biological Macromolecules 285 (2024): 138267.

[399] S. Kumbhar and M. Bhatia, “Advancements and Best Practices in Diabetic Foot Care: A Comprehensive Review of Global Progress,” Diabetes Research and Clinical Practice 217 (2024): 111845.

[400] Z. Liu, J. Xu, and X. Wang, “Bioactive Hemostatic Materials: A New Strategy for Promoting Wound Healing and Tissue Regeneration,” MedComm 6 (2025): e70113.

[401] N. M. Vecin and R. S. Kirsner, “Skin Substitutes as Treatment for Chronic Wounds: Current and Future Directions,” Frontiers in Medicine 10 (2023): 1154567.

[402] A. Chiu, D. Sharma, and F. Zhao, “Tissue Engineering-Based Strategies for Diabetic Foot Ulcer Management,” Advances in Wound Care 12 (2023): 145-167.

[403] K. Kondej, M. Zawrzykraj, K. Czerwiec, M. Deptuła, A. Tymińska, and M. Pikuła, “Bioengineering Skin Substitutes for Wound Management—Perspectives and Challenges,” International Journal of Molecular Sciences 25 (2024): 3702.

[404] O. Kammona, E. Tsanaktsidou, and C. Kiparissides, “Recent Developments in 3D-(Bio)printed Hydrogels as Wound Dressings,” Gels 10 (2024): 147.

[405] S. Choudhury and A. Das, “Advances in Generation of Three-dimensional Skin Equivalents: Pre-clinical Studies to Clinical Therapies,” Cytotherapy 23 (2021): 1-9.

[406] M. Samandari, A. Mostafavi, J. Quint, A. Memić, and A. Tamayol, “In Situ Bioprinting: Intraoperative Implementation of Regenerative Medicine,” Trends in Biotechnology 40 (2022): 1229-1247.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.