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抗炎性水凝胶对糖尿病创面愈合的研究进展
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Abstract:
糖尿病可导致多种并发症，由于高血糖、高水平的氧化应激和炎症以及易受感染等不利因素导致糖尿病慢性伤口难以愈合甚至恶化。如糖尿病足、糖尿病溃疡创面等这是糖尿病患者死亡的重要原因之一。与正常伤口相比，糖尿病创面难愈合的因素最重要的是巨噬细胞的活化失调，M1不能及时转化为M2，炎症期延长，炎症因子过度表达，阻碍转化成M2抗炎的状态，降低抗炎因子的活性，这就使得糖尿病创面炎症表达过高，不能通过自愈能让创面愈合。目前水凝胶已成为伤口敷料研究的热点材料。水凝胶能提供一个最佳的伤口水分水平的控制，因为它能够吸收多余的液体从伤口或释放水分的需要。水凝胶由于含水量高、生物相容性好、传递药物等优点，与纱布等传统敷料相比，水凝胶敷料可以提供有利于伤口愈合的湿润环境。水凝胶敷料还具有优异的组织粘附、抗菌能力、抗氧化和炎症调节作用等，在伤口敷料中具有广阔的前景。本文基于水凝胶材料的特点和糖尿病慢性创面的微环境，总结了近年来新型抗炎性水凝胶敷料治疗糖尿病慢性创面的研究进展，并探讨了目前水凝胶敷料的缺点和展望，让糖尿病伤口的个性化管理和治疗成为可能。
Diabetes can lead to a variety of complications, due to high blood sugar, high levels of oxidative stress and inflammation, as well as susceptibility to infection and other. adverse factors that make diabetic chronic wounds difficult to heal or even worsen. Such as chronic wounds, diabetic feet, diabetic ulcer wounds, etc. This is one of the important causes of death in diabetic patients. Compared with normal wounds, the most important factor that makes diabetic wounds difficult to heal is the dysactivation of macrophages, M1 cannot be converted into M2 in time, and the overexpression of inflammatory factors prevents the transformation into anti-inflammatory factors. As a result, the inflammatory expression of diabetic wounds is too high, and the wound cannot be healed through self-healing. At present, hydrogels have become a hot material in wound dressing research. Compared with traditional dressings such as gauze, hydrogel dressings can provide a moist environment conducive to wound healing due to their high water content, good biocompatibility and drug delivery. Hydrogel dressings also have excellent tissue adhesion, antibacterial ability, anti-oxidation and inflammation regulation, etc., and have broad prospects in wound dressings. Based on the characteristics of hydrogel materials and the microenvironment of diabetic chronic wounds, this paper summarizes the research progress of new anti-inflammatory hydrogel dressings for the treatment of diabetic chronic wounds in recent years, and discusses the shortcomings and prospects of current hydrogel dressings, so as to make personalized management and treatment of diabetic wounds possible.
| [1] | Bai, Q., Han, K., Dong, K., Zheng, C., Zhang, Y., Long, Q., et al. (2020) Potential Applications of Nanomaterials and Technology for Diabetic Wound Healing. International Journal of Nanomedicine, 15, 9717-9743. https://doi.org/10.2147/ijn.s276001 |
| [2] | Zhang, Y., Zhu, Y., Ma, P., Wu, H., Xiao, D., Zhang, Y., et al. (2023) Functional Carbohydrate-Based Hydrogels for Diabetic Wound Therapy. Carbohydrate Polymers, 312, Article 120823. https://doi.org/10.1016/j.carbpol.2023.120823 |
| [3] | Li, Y., Leng, Y., Liu, Y., Zhong, J., Li, J., Zhang, S., et al. (2024) Advanced Multifunctional Hydrogels for Diabetic Foot Ulcer Healing: Active Substances and Biological Functions. Journal of Diabetes, 16, e13537. https://doi.org/10.1111/1753-0407.13537 |
| [4] | Holl, J., Kowalewski, C., Zimek, Z., Fiedor, P., Kaminski, A., Oldak, T., et al. (2021) Chronic Diabetic Wounds and Their Treatment with Skin Substitutes. Cells, 10, Article 655. https://doi.org/10.3390/cells10030655 |
| [5] | Loots, M.A.M., Lamme, E.N., Zeegelaar, J., Mekkes, J.R., Bos, J.D. and Middelkoop, E. (1998) Differences in Cellular Infiltrate and Extracellular Matrix of Chronic Diabetic and Venous Ulcers versus Acute Wounds. Journal of Investigative Dermatology, 111, 850-857. https://doi.org/10.1046/j.1523-1747.1998.00381.x |
| [6] | Xiao, Y., Qian, J., Deng, X., Zhang, H., Wang, J., Luo, Z., et al. (2024) Macrophages Regulate Healing-Associated Fibroblasts in Diabetic Wound. Molecular Biology Reports, 51, Article No. 203. https://doi.org/10.1007/s11033-023-09100-1 |
| [7] | Okonkwo, U. and DiPietro, L. (2017) Diabetes and Wound Angiogenesis. International Journal of Molecular Sciences, 18, Article 1419. https://doi.org/10.3390/ijms18071419 |
| [8] | Golledge, J. and Thanigaimani, S. (2021) Novel Therapeutic Targets for Diabetes-Related Wounds or Ulcers: An Update on Preclinical and Clinical Research. Expert Opinion on Therapeutic Targets, 25, 1061-1075. https://doi.org/10.1080/14728222.2021.2014816 |
| [9] | Kimball, A., Schaller, M., Joshi, A., Davis, F.M., denDekker, A., Boniakowski, A., et al. (2018) Ly6C Hi Blood Monocyte/Macrophage Drive Chronic Inflammation and Impair Wound Healing in Diabetes Mellitus. Arteriosclerosis, Thrombosis, and Vascular Biology, 38, 1102-1114. https://doi.org/10.1161/atvbaha.118.310703 |
| [10] | Yan, C., Chen, J., Wang, C., Yuan, M., Kang, Y., Wu, Z., et al. (2022) Milk Exosomes-Mediated miR-31-5p Delivery Accelerates Diabetic Wound Healing through Promoting Angiogenesis. Drug Delivery, 29, 214-228. https://doi.org/10.1080/10717544.2021.2023699 |
| [11] | 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. https://doi.org/10.1007/s12325-014-0140-x |
| [12] | Chang, M. and Nguyen, T.T. (2021) Strategy for Treatment of Infected Diabetic Foot Ulcers. Accounts of Chemical Research, 54, 1080-1093. https://doi.org/10.1021/acs.accounts.0c00864 |
| [13] | Kharaziha, M., Baidya, A. and Annabi, N. (2021) Rational Design of Immunomodulatory Hydrogels for Chronic Wound Healing. Advanced Materials, 33, Article 2100176. https://doi.org/10.1002/adma.202100176 |
| [14] | Zhao, H., Huang, J., Li, Y., Lv, X., Zhou, H., Wang, H., et al. (2020) ROS-Scavenging Hydrogel to Promote Healing of Bacteria Infected Diabetic Wounds. Biomaterials, 258, Article 120286. https://doi.org/10.1016/j.biomaterials.2020.120286 |
| [15] | Salazar, J.J., Ennis, W.J. and Koh, T.J. (2016) Diabetes Medications: Impact on Inflammation and Wound Healing. Journal of Diabetes and Its Complications, 30, 746-752. https://doi.org/10.1016/j.jdiacomp.2015.12.017 |
| [16] | Huang, C., Dong, L., Zhao, B., Lu, Y., Huang, S., Yuan, Z., et al. (2022) Anti‐Inflammatory Hydrogel Dressings and Skin Wound Healing. Clinical and Translational Medicine, 12, e1094. https://doi.org/10.1002/ctm2.1094 |
| [17] | Hunter, S., Langemo, D.K., Anderson, J., Hanson, D. and Thompson, P. (2010) Hyperbaric Oxygen Therapy for Chronic Wounds. Advances in Skin & Wound Care, 23, 116-119. https://doi.org/10.1097/01.asw.0000363517.55135.c2 |
| [18] | Chen, L., Zheng, B., Xu, Y., Sun, C., Wu, W., Xie, X., et al. (2023) Nano Hydrogel-Based Oxygen-Releasing Stem Cell Transplantation System for Treating Diabetic Foot. Journal of Nanobiotechnology, 21, Article No. 202. https://doi.org/10.1186/s12951-023-01925-z |
| [19] | Fowler, E.M., Vesely, N., Johnson, V., Harwood, J., Tran, J. and Amberry, T. (2003) Wound Care for Patients with Diabetes. Advances in Skin & Wound Care, 16, 342-346. https://doi.org/10.1097/00129334-200312000-00009 |
| [20] | Li, M., Hou, Q., Zhong, L., Zhao, Y. and Fu, X. (2021) Macrophage Related Chronic Inflammation in Non-Healing Wounds. Frontiers in Immunology, 12, Article 681710. https://doi.org/10.3389/fimmu.2021.681710 |
| [21] | Aitcheson, S.M., Frentiu, F.D., Hurn, S.E., Edwards, K. and Murray, R.Z. (2021) Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds. Molecules, 26, Article 4917. https://doi.org/10.3390/molecules26164917 |
| [22] | Kim, S.Y. and Nair, M.G. (2019) Macrophages in Wound Healing: Activation and Plasticity. Immunology & Cell Biology, 97, 258-267. https://doi.org/10.1111/imcb.12236 |
| [23] | Sharifiaghdam, M., Shaabani, E., Faridi-Majidi, R., De Smedt, S.C., Braeckmans, K. and Fraire, J.C. (2022) Macrophages as a Therapeutic Target to Promote Diabetic Wound Healing. Molecular Therapy, 30, 2891-2908. https://doi.org/10.1016/j.ymthe.2022.07.016 |
| [24] | Liang, Y., He, J. and Guo, B. (2021) Functional Hydrogels as Wound Dressing to Enhance Wound Healing. ACS Nano, 15, 12687-12722. https://doi.org/10.1021/acsnano.1c04206 |
| [25] | Xu, Y., Hu, Q., Wei, Z., Ou, Y., Cao, Y., Zhou, H., et al. (2023) Advanced Polymer Hydrogels That Promote Diabetic Ulcer Healing: Mechanisms, Classifications, and Medical Applications. Biomaterials Research, 27, Article 36. https://doi.org/10.1186/s40824-023-00379-6 |
| [26] | Boodhoo, K., Vlok, M., Tabb, D.L., Myburgh, K.H. and van de Vyver, M. (2021) Dysregulated Healing Responses in Diabetic Wounds Occur in the Early Stages Postinjury. Journal of Molecular Endocrinology, 66, 141-155. https://doi.org/10.1530/jme-20-0256 |
| [27] | Liu, J., Qu, S., Suo, Z. and Yang, W. (2021) Functional Hydrogel Coatings. National Science Review, 8, nwaa254. https://doi.org/10.1093/nsr/nwaa254 |
| [28] | Hamidi, M., Azadi, A. and Rafiei, P. (2008) Hydrogel Nanoparticles in Drug Delivery. Advanced Drug Delivery Reviews, 60, 1638-1649. https://doi.org/10.1016/j.addr.2008.08.002 |
| [29] | Li, Q., Wang, D., Jiang, Z., Li, R., Xue, T., Lin, C., et al. (2022) Advances of Hydrogel Combined with Stem Cells in Promoting Chronic Wound Healing. Frontiers in Chemistry, 10, Article 1038839. https://doi.org/10.3389/fchem.2022.1038839 |
| [30] | Wang, C., Wang, M., Xu, T., Zhang, X., Lin, C., Gao, W., et al. (2019) Engineering Bioactive Self-Healing Antibacterial Exosomes Hydrogel for Promoting Chronic Diabetic Wound Healing and Complete Skin Regeneration. Theranostics, 9, 65-76. https://doi.org/10.7150/thno.29766 |
| [31] | Zhao, H., Huang, J., Li, Y., Lv, X., Zhou, H., Wang, H., et al. (2020) Ros-Scavenging Hydrogel to Promote Healing of Bacteria Infected Diabetic Wounds. Biomaterials, 258, Article 120286. https://doi.org/10.1016/j.biomaterials.2020.120286 |
| [32] | Xiong, Y., Chen, L., Liu, P., Yu, T., Lin, C., Yan, C., et al. (2021) All‐in‐One: Multifunctional Hydrogel Accelerates Oxidative Diabetic Wound Healing through Timed‐Release of Exosome and Fibroblast Growth Factor. Small, 18, Article 2104229. https://doi.org/10.1002/smll.202104229 |
| [33] | Chen, T., Wen, T., Dai, N. and Hsu, S. (2021) Cryogel/Hydrogel Biomaterials and Acupuncture Combined to Promote Diabetic Skin Wound Healing through Immunomodulation. Biomaterials, 269, Article 120608. https://doi.org/10.1016/j.biomaterials.2020.120608 |
| [34] | Zhu, W., Dong, Y., Xu, P., Pan, Q., Jia, K., Jin, P., et al. (2022) A Composite Hydrogel Containing Resveratrol-Laden Nanoparticles and Platelet-Derived Extracellular Vesicles Promotes Wound Healing in Diabetic Mice. Acta Biomaterialia, 154, 212-230. https://doi.org/10.1016/j.actbio.2022.10.038 |
| [35] | Qi, X., Cai, E., Xiang, Y., Zhang, C., Ge, X., Wang, J., et al. (2023) An Immunomodulatory Hydrogel by Hyperthermia‐assisted Self‐Cascade Glucose Depletion and ROS Scavenging for Diabetic Foot Ulcer Wound Therapeutics. Advanced Materials, 35, Article 2306632. https://doi.org/10.1002/adma.202306632 |
