慢性创面的病因及发病机制的研究进展
Advances in the Study of the Etiology and Pathogenesis of Chronic Wounds
DOI: 10.12677/ACM.2023.133419, PDF,   
作者: 陈鏖宇, 王一兵*:山东第一医科大学第一附属医院(山东省千佛山医院)整形外科学,山东 济南;济南市组织工程皮肤再生与创面修复临床医学研究中心,山东 济南
关键词: 慢性创面研究进展创面修复病因发病机制Chronic Wounds Research Advances Wounds Repair Etiology Pathogenesis
摘要: 慢性创面作为一类长期消耗性的皮肤系统疾病,是当前创面修复相关领域亟待解决的难题,给患者个人、社会带来了的沉重负担,该病的病因及发病机制复杂,涉及多方面因素,阐明其病因及发病机制有助于深入揭示慢性创面的致病机制并探究有效治疗靶点。本文就近年来慢性创面的病因及发病机制相关的研究进展进行综述,旨在为其分子机制及新的治疗靶点提供理论支持。
Abstract: Chronic wound, a long-term wasting disease of the skin system, is an urgent problem in wounds re-pair, which poses a heavy burden to patients and society. The aetiology and pathogenesis of this disease are complex and multifaceted, and their elucidation can help to shed light on the patho-genesis of chronic wounds and explore effective therapeutic targets. In this paper, we review the recent research progress on the etiology and pathogenesis of chronic wounds to provide theoretical support for the molecular mechanisms and new therapeutic targets.
文章引用:陈鏖宇, 王一兵. 慢性创面的病因及发病机制的研究进展[J]. 临床医学进展, 2023, 13(3): 2958-2966. https://doi.org/10.12677/ACM.2023.133419

参考文献

[1] Wang, P.H., et al. (2018) Wound Healing. Journal of the Chinese Medical Association, 81, 94-101. [Google Scholar] [CrossRef] [PubMed]
[2] Reinke, J.M. and Sorg, H. (2012) Wound Repair and Regeneration. European Surgical Research, 49, 35-43. [Google Scholar] [CrossRef] [PubMed]
[3] Han, G. and Ceilley, R. (2017) Chronic Wound Healing: A Review of Current Management and Treatments. Advances in Therapy, 34, 599-610. [Google Scholar] [CrossRef] [PubMed]
[4] Bonkemeyer Millan, S., Gan, R. and Townsend, P.E. (2019) Ve-nous Ulcers: Diagnosis and Treatment. American Family Physician, 100, 298-305.
[5] Garwood, C.S., Steinberg, J.S. and Kim, P.J. (2015) Bioengineered Alternative Tissues in Diabetic Wound Healing. Clinics in Podiatric Medicine and Surgery, 32, 121-133. [Google Scholar] [CrossRef] [PubMed]
[6] Blair, M.J., et al. (2020) Skin Struc-ture-Function Relationships and the Wound Healing Response to Intrinsic Aging. Advances in Wound Care (New Ro-chelle), 9, 127-143. [Google Scholar] [CrossRef] [PubMed]
[7] Langer, G. and Fink, A. (2014) Nutritional In-terventions for Preventing and Treating Pressure Ulcers. Cochrane Database of Systematic Reviews, 2014, Cd003216. [Google Scholar] [CrossRef
[8] Rahim, K., et al. (2017) Bacterial Contribution in Chronic-ity of Wounds. Microbial Ecology, 73, 710-721. [Google Scholar] [CrossRef] [PubMed]
[9] Gupta, S., et al. (2022) Dynamic Role of Oxygen in Wound Healing: A Microbial, Immunological, and Biochemical Perspective. Archives of Razi Institute, 77, 513-523.
[10] Wilkinson, H.N. and Hardman, M.J. (2020) Wound Healing: Cellular Mechanisms and Pathological Outcomes. Open Biology, 10, Article ID: 200223. [Google Scholar] [CrossRef] [PubMed]
[11] Olsson, M., et al. (2019) The Humanistic and Economic Burden of Chronic Wounds: A Systematic Review. Wound Repair and Regenera-tion, 27, 114-125. [Google Scholar] [CrossRef] [PubMed]
[12] Martinengo, L., et al. (2019) Prevalence of Chronic Wounds in the General Population: Systematic Review and Meta-Analysis of Observational Studies. Annals of Epidemi-ology, 29, 8-15. [Google Scholar] [CrossRef] [PubMed]
[13] Morton, L.M. and Phillips, T.J. (2016) Wound Healing and Treating Wounds: Differential Diagnosis and Evaluation of Chronic Wounds. Journal of the American Academy of Der-matology, 74, 589-605. [Google Scholar] [CrossRef] [PubMed]
[14] Baltzis, D., Eleftheriadou, I. and Veves, A. (2014) Pathogenesis and Treatment of Impaired Wound Healing in Diabetes Mellitus: New Insights. Advances in Therapy, 31, 817-836. [Google Scholar] [CrossRef] [PubMed]
[15] Berlanga-Acosta, J., et al. (2013) Glucose Toxic Effects on Gran-ulation Tissue Productive Cells: The Diabetics’ Impaired Healing. BioMed Research International, 2013, Article ID: 256043. [Google Scholar] [CrossRef] [PubMed]
[16] Arosi, I., Hiner, G. and Rajbhandari, S. (2016) Pathogenesis and Treatment of Callus in the Diabetic Foot. Current Diabetes Reviews, 12, 179-183. [Google Scholar] [CrossRef] [PubMed]
[17] Marjanovic, J., et al. (2022) Dichotomous role of miR193b-3p in Diabetic Foot Ulcers Maintains Inhibition of Healing and Suppression of Tumor Formation. Science Translational Medicine, 14, eabg8397. [Google Scholar] [CrossRef] [PubMed]
[18] Pastar, I., et al. (2010) Attenuation of the Transforming Growth Factor Beta-Signaling Pathway in Chronic Venous Ulcers. Molecular Medicine, 16, 92-101. [Google Scholar] [CrossRef] [PubMed]
[19] Stojadinovic, O., et al. (2014) Deregulation of Epidermal Stem Cell Niche Contributes to Pathogenesis of Nonhealing Venous Ulcers. Wound Repair and Regeneration, 22, 220-227. [Google Scholar] [CrossRef] [PubMed]
[20] Koreyba, K., et al. (2022) Prognostic Value of Histological and Immuno-histochemical Data in Diabetic Foot Ulcers. Journal of Clinical Medicine, 11, 7202. [Google Scholar] [CrossRef] [PubMed]
[21] Maione, A.G., et al. (2015) Three-Dimensional Human Tissue Models That Incorporate Diabetic Foot Ulcer-Derived Fibroblasts Mimic in Vivo Features of Chronic Wounds. Tissue Engineer-ing Part C: Methods, 21, 499-508. [Google Scholar] [CrossRef] [PubMed]
[22] Sahin, E., et al. (2011) Telomere Dysfunction Induces Metabolic and Mitochondrial Compromise. Nature, 470, 359-365. [Google Scholar] [CrossRef] [PubMed]
[23] Prattichizzo, F., et al. (2018) Short-Term Sustained Hyperglycaemia Fosters an Archetypal Senescence-Associated Secretory Phenotype in Endothelial Cells and Macrophages. Redox Biology, 15, 170-181. [Google Scholar] [CrossRef] [PubMed]
[24] Gkogkolou, P. and Bohm, M. (2012) Advanced Glycation End Products: Key Players in Skin Aging? Dermato-Endocrinology, 4, 259-270. [Google Scholar] [CrossRef] [PubMed]
[25] Hicks, C.W. and Selvin, E. (2019) Epidemiology of Peripheral Neuropa-thy and Lower Extremity Disease in Diabetes. Current Diabetes Reports, 19, 86. [Google Scholar] [CrossRef] [PubMed]
[26] Soyoye, D.O., et al. (2021) Diabetes and Peripheral Artery Dis-ease: A Review. World Journal of Diabetes, 12, 827-838. [Google Scholar] [CrossRef] [PubMed]
[27] Jaul, E., et al. (2018) An Overview of Co-Morbidities and the Development of Pressure Ulcers among Older Adults. BMC Geriatrics, 18, 305. [Google Scholar] [CrossRef] [PubMed]
[28] Zaidi, S.R.H. and Sharma, S. (2022) Pressure Ulcer. StatPearls Publishing, Treasure Island.
[29] Wong, V.W., et al. (2011) Focal Adhesion Kinase Links Mechanical Force to Skin Fibrosis via Inflammatory Signaling. Nature Medicine, 18, 148-152. [Google Scholar] [CrossRef] [PubMed]
[30] 余墨声, 等. 慢性创面的临床治疗进展[J]. 临床外科杂志, 2016, 24(3): 165-167.
[31] Demidova-Rice, T.N., Ham-blin, M.R. and Herman, I.M. (2012) Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 1: Normal and Chronic Wounds: Biology, Causes, and Approaches to Care. Advances in Skin & Wound Care, 25, 304-314. [Google Scholar] [CrossRef
[32] Word, R. (2010) Medical and Surgical Therapy for Advanced Chronic Venous Insufficiency. Surgical Clinics of North America, 90, 1195-1214. [Google Scholar] [CrossRef] [PubMed]
[33] Bowers, S. and Franco, E. (2020) Chronic Wounds: Evaluation and Management. American Family Physician, 101, 159-166.
[34] Fowkes, F.G., et al. (2013) Comparison of Global Esti-mates of Prevalence and Risk Factors for Peripheral Artery Disease in 2000 and 2010: A Systematic Review and Analy-sis. The Lancet, 382, 1329-1340. [Google Scholar] [CrossRef
[35] Stoekenbroek, R.M., et al. (2015) Is Additional Hyperbaric Oxygen Therapy Cost-Effective for Treating Ischemic Diabetic Ulcers? Study Protocol for the Dutch DAMOCLES Mul-ticenter Randomized Clinical Trial? Journal of Diabetes, 7, 125-132. [Google Scholar] [CrossRef] [PubMed]
[36] Zhao, R., et al. (2016) Inflammation in Chronic Wounds. Interna-tional Journal of Molecular Sciences, 17, 2085. [Google Scholar] [CrossRef] [PubMed]
[37] Gabriel, A., et al. (2020) Infection and Inflammation in the Wound En-vironment: Addressing Issues of Delayed Wound Healing with Advanced Wound Dressings. Wounds, 32, S1-S17.
[38] Stojadinovic, O., et al. (2013) Increased Number of Langerhans Cells in the Epidermis of Diabetic Foot Ulcers Correlates with Healing Outcome. Immunologic Research, 57, 222-228. [Google Scholar] [CrossRef] [PubMed]
[39] Sindrilaru, A., et al. (2011) An Unrestrained Proinflammatory M1 Macrophage Population Induced by Iron Impairs Wound Healing in Humans and Mice. Journal of Clinical Investigation, 121, 985-997. [Google Scholar] [CrossRef
[40] Saffarzadeh, M., et al. (2012) Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: A Predominant Role of Histones. PLOS ONE, 7, e32366. [Google Scholar] [CrossRef] [PubMed]
[41] Wong, S.L., et al. (2015) Diabetes Primes Neutrophils to Un-dergo NETosis, Which Impairs Wound Healing. Nature Medicine, 21, 815-819. [Google Scholar] [CrossRef] [PubMed]
[42] Khanna, S., et al. (2010) Macrophage Dysfunction Impairs Resolution of In-flammation in the Wounds of Diabetic Mice. PLOS ONE, 5, e9539. [Google Scholar] [CrossRef] [PubMed]
[43] Lecube, A., et al. (2011) Phagocytic Activity Is Impaired in Type 2 Diabetes Mellitus and Increases after Metabolic Improvement. PLOS ONE, 6, e23366. [Google Scholar] [CrossRef] [PubMed]
[44] Pettersson, U.S., et al. (2011) Increased Recruitment but Im-paired Function of Leukocytes during Inflammation in Mouse Models of Type 1 and Type 2 Diabetes. PLOS ONE, 6, e22480. [Google Scholar] [CrossRef] [PubMed]
[45] Bannon, P., et al. (2013) Diabetes Induces Stable In-trinsic Changes to Myeloid Cells That Contribute to Chronic Inflammation during Wound Healing in Mice. Disease Models & Mechanisms, 6 1434-1447. [Google Scholar] [CrossRef] [PubMed]
[46] Moura, J., et al. (2017) Impaired T-Cell Differentiation in Diabetic Foot Ulceration. Cellular & Molecular Immunology, 14, 758-769. [Google Scholar] [CrossRef] [PubMed]
[47] Dormer, K.J. and Gkotsoulias, E. (2022) The Role of Hemodynamic Shear Stress in Healing Chronic Wounds. Wounds, 34, 254-262. [Google Scholar] [CrossRef] [PubMed]
[48] 唐乾利, 等. MEBT/MEBO对血管内皮细胞粗面内质网影响的实验研究[J]. 中国烧伤创疡杂志, 2010, 22(4): 252-257.
[49] 唐乾利, 狄钾骐, 李杰辉, 郭璐, 曾娟妮, 敖小青, 付军, 韩珊珊. MEBO/MEBT对大鼠体表慢性难愈性溃疡创面VEGF/bFGF表达的影响[C]//第七届中华中医药学会中医外治学术年会, 2011: 311-317.
[50] Wicks, K., Torbica, T. and Mace, K.A. (2014) Myeloid Cell Dysfunc-tion and the Pathogenesis of the Diabetic Chronic Wound. Seminars in Immunology, 26, 341-353. [Google Scholar] [CrossRef] [PubMed]
[51] Krisp, C., et al. (2013) Proteome Analysis Reveals Antiangiogenic Environments in Chronic Wounds of Diabetes Mellitus Type 2 Patients. Proteomics, 13, 2670-2681. [Google Scholar] [CrossRef] [PubMed]
[52] Trujillo, A.N., et al. (2015) Demonstration of the Rat Ischemic Skin Wound Model. Journal of Visualized Experiments, No. 98, e52637. [Google Scholar] [CrossRef] [PubMed]
[53] Darby, I.A. and Hewitson, T.D. (2016) Hypoxia in Tissue Repair and Fibrosis. Cell and Tissue Research, 365, 553-562. [Google Scholar] [CrossRef] [PubMed]
[54] Guo, S. and Dipietro, L.A. (2010) Factors Affecting Wound Healing. Journal of Dental Research, 89, 219-229. [Google Scholar] [CrossRef] [PubMed]
[55] Schreml, S., et al. (2010) Oxygen in Acute and Chronic Wound Healing. British Journal of Dermatology, 163, 257-268. [Google Scholar] [CrossRef] [PubMed]
[56] Kalan, L.R., et al. (2019) Strain- and Species-Level Varia-tion in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy. Cell Host & Microbe, 25, 641-655e5. [Google Scholar] [CrossRef] [PubMed]
[57] Loesche, M., et al. (2017) Temporal Stability in Chronic Wound Microbiota Is Associated with Poor Healing. Journal of Investigative Dermatology, 137, 237-244. [Google Scholar] [CrossRef] [PubMed]
[58] Clinton, A. and Carter, T. (2015) Chronic Wound Biofilms: Patho-genesis and Potential Therapies. Laboratory Medicine, 46, 277-284. [Google Scholar] [CrossRef
[59] Zhao, G., et al. (2013) Biofilms and Inflammation in Chronic Wounds. Advances in Wound Care (New Rochelle), 2, 389-399. [Google Scholar] [CrossRef] [PubMed]
[60] Versey, Z., et al. (2021) Biofilm-Innate Immune Interface: Contri-bution to Chronic Wound Formation. Frontiers in Immunology, 12, Article ID: 648554. [Google Scholar] [CrossRef] [PubMed]
[61] Guan, H., et al. (2021) Distribution and Antibiotic Resistance Patterns of Pathogenic Bacteria in Patients with Chronic Cutaneous Wounds in China. Frontiers in Medicine (Lausanne), 8, Article ID: 609584. [Google Scholar] [CrossRef] [PubMed]
[62] Pouget, C., et al. (2020) Biofilms in Diabetic Foot Ulcers: Signifi-cance and Clinical Relevance. Microorganisms, 8, 1580. [Google Scholar] [CrossRef] [PubMed]
[63] Wilkinson, H.N. and Hardman, M.J. (2021) Wound Senes-cence: A Functional Link between Diabetes and Ageing? Experimental Dermatology, 30, 68-73. [Google Scholar] [CrossRef] [PubMed]
[64] Gabuardi, T.L., Lee, H.G. and Lee, K.J. (2022) Role of Senescent Cells in the Motile Behavior of Active, Non-Senescent Cells in Confluent Populations. Scientific Reports, 12, 3857. [Google Scholar] [CrossRef] [PubMed]
[65] Jacome Burbano, M.S., Cherfils-Vicini, J. and Gilson, E. (2021) Neutrophils: Mediating TelOxidation and Senescence. The EMBO Journal, 40, e108164. [Google Scholar] [CrossRef] [PubMed]
[66] Baud, S., et al. (2013) Elastin Peptides in Aging and Pathological Conditions. BioMolecular Concepts, 4, 65-76. [Google Scholar] [CrossRef] [PubMed]
[67] Park, H.Y., et al. (2011) A Long-Standing Hyperglycaemic Condition Impairs Skin Barrier by Accelerating Skin Ageing Process. Experimental Dermatology, 20, 969-974. [Google Scholar] [CrossRef] [PubMed]
[68] Bermudez, D.M., et al. (2011) Impaired Biomechanical Properties of Diabetic Skin Implications in Pathogenesis of Diabetic Wound Complications. The American Journal of Pathology, 178, 2215-2223. [Google Scholar] [CrossRef] [PubMed]
[69] Childs, B.G., et al. (2015) Cellular Senescence in Aging and Age-Related Disease: From Mechanisms to Therapy. Nature Medicine, 21, 1424-1435. [Google Scholar] [CrossRef] [PubMed]
[70] Wilkinson, H.N., et al. (2016) Comparing the Effectiveness of Polymer De-briding Devices Using a Porcine Wound Biofilm Model. Advances in Wound Care (New Rochelle), 5, 475-485. [Google Scholar] [CrossRef] [PubMed]
[71] Farahani, M. and Shafiee, A. (2021) Wound Healing: From Passive to Smart Dressings. Advanced Healthcare Materials, 10, e2100477. [Google Scholar] [CrossRef] [PubMed]
[72] Liang, Y., He, J. and Guo, B. (2021) Functional Hydrogels as Wound Dressing to Enhance Wound Healing. ACS Nano, 15, 12687-12722. [Google Scholar] [CrossRef] [PubMed]
[73] Cheng, H., et al. (2021) Sprayable Hydrogel Dressing Accelerates Wound Healing with Combined Reactive Oxygen Species-Scavenging and Antibacterial Abilities. Acta Biomaterialia, 124, 219-232. [Google Scholar] [CrossRef] [PubMed]
[74] Brownhill, V.R., et al. (2021) Pre-Clinical Assessment of Sin-gle-Use Negative Pressure Wound Therapy during In Vivo Porcine Wound Healing. Advances in Wound Care (New Ro-chelle), 10, 345-356. [Google Scholar] [CrossRef] [PubMed]
[75] Tetteh-Quarshie, S., Blough, E.R. and Jones, C.B. (2021) Exploring Dendrimer Nanoparticles for Chronic Wound Healing. Frontiers in Medical Technology, 3, Article ID: 661421. [Google Scholar] [CrossRef] [PubMed]
[76] Stratmann, B., et al. (2020) Effect of Cold Atmospheric Plasma Therapy vs Standard Therapy Placebo on Wound Healing in Patients with Diabetic Foot Ulcers: A Randomized Clinical Trial. JAMA Network Open, 3, e2010411. [Google Scholar] [CrossRef] [PubMed]
[77] Homaeigohar, S., Li, M. and Boccaccini, A.R. (2022) Bioactive Glass-Based Fibrous Wound Dressings. Burns & Trauma, 10, tkac038. [Google Scholar] [CrossRef] [PubMed]
[78] Pinto, A.M., et al. (2020) Bacteriophages for Chronic Wound Treat-ment: from Traditional to Novel Delivery Systems. Viruses, 12, 235. [Google Scholar] [CrossRef] [PubMed]
[79] Hickson, L.J., et al. (2019) Senolytics Decrease Senescent Cells in Hu-mans: Preliminary Report from a Clinical Trial of Dasatinib plus Quercetin in Individuals with Diabetic Kidney Disease. EBioMedicine, 47, 446-456. [Google Scholar] [CrossRef] [PubMed]
[80] Hohmann, M.S., et al. (2019) Quercetin Enhances Lig-and-Induced Apoptosis in Senescent Idiopathic Pulmonary Fibrosis Fibroblasts and Reduces Lung Fibrosis in Vivo. The American Journal of Respiratory Cell and Molecular Biology, 60, 28-40. [Google Scholar] [CrossRef
[81] Chittasupho, C., et al. (2021) Effects of Quercetin and Curcumin Combination on Antibacterial, Antioxidant, in Vitro Wound Healing and Migration of Human Dermal Fibroblast Cells. International Journal of Molecular Sciences, 23, 142. [Google Scholar] [CrossRef] [PubMed]
[82] Wilkinson, H.N., et al. (2019) Elevated Local Senescence in Diabetic Wound Healing Is Linked to Pathological Repair via CXCR2. Jour-nal of Investigative Dermatology, 139, 1171-1181.e6. [Google Scholar] [CrossRef] [PubMed]
[83] An, Y., et al. (2021) Exosomes from Adipose-Derived Stem Cells and Application to Skin Wound Healing. Cell Proliferation, 54, e12993. [Google Scholar] [CrossRef] [PubMed]
[84] Sharma, P., et al. (2021) Stem Cells and Growth Factors-Based Delivery Approaches for Chronic Wound Repair and Regeneration: A Promise to Heal from Within. Life Sciences, 268, Article ID: 118932. [Google Scholar] [CrossRef] [PubMed]
[85] Veith, A.P., et al. (2019) Therapeutic Strategies for Enhancing An-giogenesis in Wound Healing. Advanced Drug Delivery Reviews, 146, 97-125. [Google Scholar] [CrossRef] [PubMed]