Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2023, Vol. 43 Issue (2/3): 54-63    DOI: 10.13523/j.cb.2208034
新型药物递送系统研发与应用专题     
应用于糖尿病溃疡的载药静电纺丝敷料研究进展*
文小虎,马诗文,姜世豪,党政,赵鹏翔**()
北京工业大学环境与生命学部 北京 100124
Research Progress of Drug-loaded Electrospinning Dressings for Diabetic Ulcers
WEN Xiao-hu,MA Shi-wen,JIANG Shi-hao,DANG Zheng,ZHAO Peng-xiang**()
Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
 全文: PDF(1016 KB)   HTML
摘要:

糖尿病溃疡是糖尿病最为严重的并发症之一,具有愈合周期长、难以治愈、复发率高等特点。敷料作为糖尿病溃疡治疗的重要环节不能被忽视。理想的创面敷料应具有止血、抗菌、生物相容性高等特性,传统敷料远不能满足糖尿病伤口需要。随着纳米技术的发展,采用静电纺丝技术制备的纳米纤维敷料在糖尿病溃疡的治疗中取得了一定进展。因此,基于对糖尿病溃疡难愈机制的理解,对静电纺丝纳米纤维敷料的基质材料、负载物质及研究现状进行了综述,为其进一步研究提供参考。

关键词: 糖尿病伤口敷料静电纺丝    
Abstract:

Diabetic ulcer is one of the most serious complications of diabetes mellitus. It has the characteristics of long healing cycle, difficulty in cure and high recurrence rate. Dressing as an important part of the treatment of diabetic ulcers cannot be ignored. Ideal wound dressings should have characteristics of hemostasis, antibacterial property and high biocompatibility, while traditional dressings are far from meeting the needs of diabetic wounds. With the development of nanotechnology, nanofiber dressings prepared by electrospinning technology have made some progress in the treatment of diabetic ulcers. Therefore, based on the understanding of the refractory mechanism of diabetic ulcers, the matrix materials, loading materials and research status of electrospun nanofiber dressings were reviewed, so as to provide reference for further research.

Key words: Diabetic wounds    Dressing    Electrostatic spinning
收稿日期: 2022-08-25 出版日期: 2023-03-31
ZTFLH:  Q819  
基金资助: *军委后勤保障部开放研究重点项目(BHJ17L018)
通讯作者: **赵鹏翔     E-mail: zpx@bjut.edu.cn
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
文小虎
马诗文
姜世豪
党政
赵鹏翔

引用本文:

文小虎, 马诗文, 姜世豪, 党政, 赵鹏翔. 应用于糖尿病溃疡的载药静电纺丝敷料研究进展*[J]. 中国生物工程杂志, 2023, 43(2/3): 54-63.

WEN Xiao-hu, MA Shi-wen, JIANG Shi-hao, DANG Zheng, ZHAO Peng-xiang. Research Progress of Drug-loaded Electrospinning Dressings for Diabetic Ulcers. China Biotechnology, 2023, 43(2/3): 54-63.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2208034        https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I2/3/54

图1  影响糖尿病溃疡愈合主要因素示意图
图2  载药静电纺丝敷料制备示意图
材料 聚合物 参考文献
合成聚合物 聚己内酯(polycaprolactone,PCL) [49?????????-59]
聚乙烯醇(polyvinyl alcohol,PVA) [60???-64]
乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA] [65?-67]
聚L-丙交酯-己内酯[poly(L-lactide-co-caprolactone),PLCL] [68-69]
聚乙烯吡咯烷酮(polyvinyl pyrrolidone,PVP) [51,70]
聚乙二醇甲醚(methoxypolyethylene glycols,m-PEG) [70]
聚醚氨酯脲[poly(ester-urethane)urea,PEUU] [71]
天然聚合物 明胶(gelatin,GEL) [49,51-52,55?-57,59,67]
壳聚糖(chitosan,CTS) [51,63-64]
丝素蛋白(silk fibroin,SF) [69,71]
醋酸纤维素(cellulose acetate,CA) [54,72]
胶原蛋白(collagen,CO) [50]
浒苔多糖(enteromorpha polysaccharide,EPP) [60]
玻尿酸(hyaluronic acid,HA) [68]
玉米醇溶蛋白(zein) [72]
褐藻多糖(brown alga-derived polysaccharide,BAP) [61]
表1  用于糖尿病溃疡的静电纺丝敷料基质材料
类别 活性物质 活性分子 参考文献
天然活性物质 植物提取物 牛至油、芝麻酚、厚朴酚、柴胡皂苷、白头翁苷、龙胆苦苷、百里醌、熊果酸、阿魏酸 [54,62,64,67-68,70?-72]
生物分子 生长因子 血小板衍生生长因子(platelet derived growth factor,PDGF) [65]
干细胞 骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs) [57]
纳米金属粒子 金属氧化物 MgO、ZnO [49,55,68]
金属粒子 铜基金属骨架HKUST-1、蛭石纳米片 [56,58]
药物 抗生素 万古霉素、庆大霉素、阿莫西林、多西环素、头孢氨苄 [49-50,65]
抗糖尿病 吡格列酮、二甲双胍、格列苯脲、胰岛素、利拉鲁肽 [51-52,66-67]
解毒剂 谷胱甘肽、去铁胺 [53,59]
表2  用于糖尿病溃疡的静电纺丝敷料负载的活性物质
[1] International Diabetes Federation. IDF Diabetes Atlas 10th Edition. Brussels, Belgium: International Diabetes Federation, 2021.[2022-05-15]. http://www.diabetesatlas.org.
[2] Armstrong D G, Boulton A J M, Bus S A. Diabetic foot ulcers and their recurrence. The New England Journal of Medicine, 2017, 376(24): 2367-2375.
doi: 10.1056/NEJMra1615439 pmid: 28614678
[3] Lavery L A, Armstrong D G, Wunderlich R P, et al. Diabetic foot syndrome. Diabetes Care, 2003, 26(5): 1435-1438.
doi: 10.2337/diacare.26.5.1435
[4] Walsh J W, Hoffstad O J, Sullivan M O, et al. Association of diabetic foot ulcer and death in a population-based cohort from the United Kingdom. Diabetic Medicine: a Journal of the British Diabetic Association, 2016, 33(11): 1493-1498.
doi: 10.1111/dme.13054 pmid: 26666583
[5] Bowling F L, Rashid S T, Boulton A J M. Preventing and treating foot complications associated with diabetes mellitus. Nature Reviews Endocrinology, 2015, 11(10): 606-616.
doi: 10.1038/nrendo.2015.130 pmid: 26284447
[6] Jeffcoate W J, Vileikyte L, Boyko E J, et al. Current challenges and opportunities in the prevention and management of diabetic foot ulcers. Diabetes Care, 2018, 41(4): 645-652.
doi: 10.2337/dc17-1836 pmid: 29559450
[7] Rodrigues M, Kosaric N, Bonham C A, et al. Wound healing: a cellular perspective. Physiological Reviews, 2019, 99(1): 665-706.
doi: 10.1152/physrev.00067.2017 pmid: 30475656
[8] Godo S, Shimokawa H. Endothelial functions. Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37(9): e108-e114.
[9] Pierce G F, Mustoe T A, Altrock B W, et al. Role of platelet-derived growth factor in wound healing. Journal of Cellular Biochemistry, 1991, 45(4): 319-326.
doi: 10.1002/jcb.240450403 pmid: 2045423
[10] Pool J G. Normal hemostatic mechanisms: a review. The American Journal of Medical Technology, 1977, 43(8): 776-780.
pmid: 888856
[11] Jorch S K, Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nature Medicine, 2017, 23(3): 279-287.
doi: 10.1038/nm.4294 pmid: 28267716
[12] Yipp B G, Kubes P. NETosis: how vital is it? Blood, 2013, 122(16): 2784-2794.
doi: 10.1182/blood-2013-04-457671 pmid: 24009232
[13] Wilgus T A, Roy S, McDaniel J C. Neutrophils and wound repair: positive actions and negative reactions. Advances in Wound Care, 2013, 2(7): 379-388.
doi: 10.1089/wound.2012.0383 pmid: 24527354
[14] Park J E, Barbul A. Understanding the role of immune regulation in wound healing. American Journal of Surgery, 2004, 187(5A): 11S-16S.
pmid: 15147986
[15] Slauch J M. How does the oxidative burst of macrophages kill bacteria? Still an open question. Molecular Microbiology, 2011, 80(3): 580-583.
doi: 10.1111/j.1365-2958.2011.07612.x pmid: 21375590
[16] DiPietro L A, Polverini P J, Rahbe S M, et al. Modulation of JE/MCP-1 expression in dermal wound repair. The American Journal of Pathology, 1995, 146(4): 868-875.
[17] Oskeritzian C A. Mast cells and wound healing. Advances in Wound Care, 2012, 1(1): 23-28.
doi: 10.1089/wound.2011.0357 pmid: 24527274
[18] Wang Z P, Lai Y P, Bernard J J, et al. Skin mast cells protect mice against vaccinia virus by triggering mast cell receptor S1PR2 and releasing antimicrobial peptides. Journal of Immunology (Baltimore, Md: 1950), 2012, 188(1): 345-357.
doi: 10.4049/jimmunol.1101703
[19] Jameson J M, Cauvi G, Witherden D A, et al. A keratinocyte-responsive gamma delta TCR is necessary for dendritic epidermal T cell activation by damaged keratinocytes and maintenance in the epidermis. Journal of Immunology (Baltimore, Md: 1950), 2004, 172(6): 3573-3579.
doi: 10.4049/jimmunol.172.6.3573
[20] Zhang J G, Czabotar P E, Policheni A N, et al. The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity, 2012, 36(4): 646-657.
doi: 10.1016/j.immuni.2012.03.009
[21] Bratton D L, Henson P M. Neutrophil clearance: when the party is over, clean-up begins. Trends in Immunology, 2011, 32(8): 350-357.
doi: 10.1016/j.it.2011.04.009 pmid: 21782511
[22] de Oliveira S, Rosowski E E, Huttenlocher A. Neutrophil migration in infection and wound repair: going forward in reverse. Nature Reviews Immunology, 2016, 16(6): 378-391.
doi: 10.1038/nri.2016.49 pmid: 27231052
[23] Gurtner G C, Werner S, Barrandon Y, et al. Wound repair and regeneration. Nature, 2008, 453(7193): 314-321.
doi: 10.1038/nature07039
[24] Galli S J, Borregaard N, Wynn T A. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nature Immunology, 2011, 12(11): 1035-1044.
doi: 10.1038/ni.2109 pmid: 22012443
[25] Willenborg S, Lucas T, van Loo G, et al. CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair. Blood, 2012, 120(3): 613-625.
doi: 10.1182/blood-2012-01-403386 pmid: 22577176
[26] Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science, 1997, 275(5302): 964-967.
doi: 10.1126/science.275.5302.964 pmid: 9020076
[27] Fantin A, Vieira J M, Gestri G, et al. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood, 2010, 116(5): 829-840.
doi: 10.1182/blood-2009-12-257832 pmid: 20404134
[28] Outtz H H, Tattersall I W, Kofler N M, et al. Notch1 controls macrophage recruitment and Notch signaling is activated at sites of endothelial cell anastomosis during retinal angiogenesis in mice. Blood, 2011, 118(12): 3436-3439.
doi: 10.1182/blood-2010-12-327015 pmid: 21795743
[29] Marangoni R G, Korman B D, Wei J, et al. Myofibroblasts in murine cutaneous fibrosis originate from adiponectin-positive intradermal progenitors. Arthritis & Rheumatology (Hoboken, N J), 2015, 67(4): 1062-1073.
[30] Wernig G, Chen S Y, Cui L, et al. Unifying mechanism for different fibrotic diseases. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(18): 4757-4762.
[31] Sheehan P, Jones P, Caselli A, et al. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care, 2003, 26(6): 1879-1882.
pmid: 12766127
[32] Deng L L, Du C Z, Song P Y, et al. The role of oxidative stress and antioxidants in diabetic wound healing. Oxidative Medicine and Cellular Longevity, 2021, 2021: 8852759.
[33] Vlassara H, Uribarri J. Advanced glycation end products (AGE) and diabetes: cause, effect, or both? Current Diabetes Reports, 2014, 14(1): 453.
doi: 10.1007/s11892-013-0453-1 pmid: 24292971
[34] Liu T, Zhang L Y, Joo D, et al. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy, 2017, 2: 17023.
doi: 10.1038/sigtrans.2017.23
[35] Kang H J, Kumar S, D’Elia A, et al. Self-assembled elastin-like polypeptide fusion protein coacervates as competitive inhibitors of advanced glycation end-products enhance diabetic wound healing. Journal of Controlled Release, 2021, 333: 176-187.
doi: 10.1016/j.jconrel.2021.03.032
[36] Kang R, Tang D L, Lotze M T, et al. RAGE regulates autophagy and apoptosis following oxidative injury. Autophagy, 2011, 7(4): 442-444.
pmid: 21317562
[37] Guo Y Y, Lin C, Xu P, et al. AGEs induced autophagy impairs cutaneous wound healing via stimulating macrophage polarization to M1 in diabetes. Scientific Reports, 2016, 6: 36416.
doi: 10.1038/srep36416 pmid: 27805071
[38] Basta G, Schmidt A M, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovascular Research, 2004, 63(4): 582-592.
doi: 10.1016/j.cardiores.2004.05.001 pmid: 15306213
[39] Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. The Journal of Clinical Investigation, 2007, 117(5): 1219-1222.
doi: 10.1172/JCI32169
[40] Catrina S B, Zheng X W. Disturbed hypoxic responses as a pathogenic mechanism of diabetic foot ulcers. Diabetes/Metabolism Research and Reviews, 2016, 32(Suppl 1): 179-185.
doi: 10.1002/dmrr.2742
[41] Catrina S B, Zheng X W. Hypoxia and hypoxia-inducible factors in diabetes and its complications. Diabetologia, 2021, 64(4): 709-716.
doi: 10.1007/s00125-021-05380-z
[42] Noor S, Zubair M, Ahmad J. Diabetic foot ulcer:a review on pathophysiology, classification and microbial etiology. Diabetes & Metabolic Syndrome, 2015, 9(3): 192-199.
[43] Versey Z, da Cruz Nizer W S, Russell E, et al. Biofilm-innate immune interface: contribution to chronic wound formation. Frontiers in Immunology, 2021, 12: 648554.
doi: 10.3389/fimmu.2021.648554
[44] Ali L L, Khambaty F, Diachenko G. Investigating the suitability of the Calgary Biofilm Device for assessing the antimicrobial efficacy of new agents. Bioresource Technology, 2006, 97(15): 1887-1893.
pmid: 16256346
[45] Xie X Y, Liu X Q, Li Y L, et al. Advanced glycation end products enhance biofilm formation by promoting extracellular DNA release through sigB upregulation in Staphylococcus aureus. Frontiers in Microbiology, 2020, 11: 1479.
doi: 10.3389/fmicb.2020.01479
[46] Liang Y P, He J H, Guo B L. Functional hydrogels as wound dressing to enhance wound healing. ACS Nano, 2021, 15(8): 12687-12722.
doi: 10.1021/acsnano.1c04206 pmid: 34374515
[47] Gao Z J, Wang Q X, Yao Q Q, et al. Application of electrospun nanofiber membrane in the treatment of diabetic wounds. Pharmaceutics, 2021, 14(1): 6.
doi: 10.3390/pharmaceutics14010006
[48] Ghanavati Z, Neisi N, Bayati V, et al. The influence of substrate topography and biomaterial substance on skin wound healing. Anatomy & Cell Biology, 2015, 48(4): 251-257.
[49] Jafari A, Amirsadeghi A, Hassanajili S, et al. Bioactive antibacterial bilayer PCL/gelatin nanofibrous scaffold promotes full-thickness wound healing. International Journal of Pharmaceutics, 2020, 583: 119413.
doi: 10.1016/j.ijpharm.2020.119413
[50] Chang T, Yin H Y, Yu X, et al. 3D PCL/collagen nanofibrous medical dressing for one-time treatment of diabetic foot ulcers. Colloids and Surfaces B: Biointerfaces, 2022, 214: 112480.
doi: 10.1016/j.colsurfb.2022.112480
[51] Cam M E, Ertas B, Alenezi H, et al. Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: an in vitro and in vivo evaluation study. Materials Science and Engineering: C, 2021, 119: 111586.
doi: 10.1016/j.msec.2020.111586
[52] Yu B R, He C H, Wang W B, et al. Asymmetric wettable composite wound dressing prepared by electrospinning with bioinspired micropatterning enhances diabetic wound healing. ACS Applied Bio Materials, 2020, 3(8): 5383-5394.
doi: 10.1021/acsabm.0c00695 pmid: 35021712
[53] Khandaker M, Alkadhem N, Progri H, et al. Glutathione immobilized polycaprolactone nanofiber mesh as a dermal drug delivery mechanism for wound healing in a diabetic patient. Processes, 2022, 10(3): 512.
doi: 10.3390/pr10030512
[54] Anand S, Pandey P, Begum M Y, et al. Electrospun biomimetic multifunctional nanofibers loaded with ferulic acid for enhanced antimicrobial and wound-healing activities in STZ-induced diabetic rats. Pharmaceuticals (Basel, Switzerland), 2022, 15(3): 302.
[55] Liu M Y, Wang R L, Liu J J, et al. Incorporation of magnesium oxide nanoparticles into electrospun membranes improves pro-angiogenic activity and promotes diabetic wound healing. Biomaterials Advances, 2022, 133: 112609.
doi: 10.1016/j.msec.2021.112609
[56] Zhang P J, Li Y, Tang Y H, et al. Copper-based metal-organic framework as a controllable nitric oxide-releasing vehicle for enhanced diabetic wound healing. ACS Applied Materials & Interfaces, 2020, 12(16): 18319-18331.
[57] Chen S X, Wang H J, Su Y J, et al. Mesenchymal stem cell-laden, personalized 3D scaffolds with controlled structure and fiber alignment promote diabetic wound healing. Acta Biomaterialia, 2020, 108: 153-167.
doi: S1742-7061(20)30176-8 pmid: 32268240
[58] Huang X T, Wang Q R, Mao R Y, et al. Two-dimensional nanovermiculite and polycaprolactone electrospun fibers composite scaffolds promoting diabetic wound healing. Journal of Nanobiotechnology, 2022, 20(1): 343.
doi: 10.1186/s12951-022-01556-w pmid: 35883146
[59] Zhong H L, Huang J, Luo M C, et al. Near-field electrospun PCL fibers/GelMA hydrogel composite dressing with controlled deferoxamine-release ability and retiform surface for diabetic wound healing. Nano Research, 2022: 1-14.
[60] Guo L L, Guan N, Miao W J, et al. An electrospun scaffold loaded with an Enteromorpha polysaccharide for accelerated wound healing in diabetic mice. Marine Drugs, 2022, 20(2): 95.
doi: 10.3390/md20020095
[61] Huang X L, Guan N, Li Q. A marine-derived anti-inflammatory scaffold for accelerating skin repair in diabetic mice. Marine Drugs, 2021, 19(9): 496.
doi: 10.3390/md19090496
[62] Yu M, Tang P F, Tang Y H, et al. Breathable, moisturizing, anti-oxidation SSD-PG-PVA/KGM fibrous membranes for accelerating diabetic wound tissue regeneration. ACS Applied Bio Materials, 2022, 5(6): 2894-2901.
doi: 10.1021/acsabm.2c00255 pmid: 35593099
[63] Zhang H, Zhang M Y, Wang X M, et al. Electrospun multifunctional nanofibrous mats loaded with bioactive anemoside B 4 for accelerated wound healing in diabetic mice. Drug Delivery, 2022, 29(1): 174-185.
doi: 10.1080/10717544.2021.2021319 pmid: 34978237
[64] Lv H Y, Zhao M, Li Y R, et al. Electrospun chitosan-polyvinyl alcohol nanofiber dressings loaded with bioactive ursolic acid promoting diabetic wound healing. Nanomaterials (Basel, Switzerland), 2022, 12(17): 2933.
[65] Lee C H, Liu K S, Cheng C W, et al. Codelivery of sustainable antimicrobial agents and platelet-derived growth factor via biodegradable nanofibers for repair of diabetic infectious wounds. ACS Infectious Diseases, 2020, 6(10): 2688-2697.
doi: 10.1021/acsinfecdis.0c00321
[66] Lee C H, Hung K C, Hsieh M J, et al. Core-shell insulin-loaded nanofibrous scaffolds for repairing diabetic wounds. Nanomedicine: Nanotechnology, Biology, and Medicine, 2020, 24: 102123.
doi: 10.1016/j.nano.2019.102123
[67] Yu M Y, Huang J H, Zhu T H, et al. Liraglutide-loaded PLGA/gelatin electrospun nanofibrous mats promote angiogenesis to accelerate diabetic wound healing via the modulation of miR-29b-3p. Biomaterials Science, 2020, 8(15): 4225-4238.
doi: 10.1039/d0bm00442a pmid: 32578587
[68] Khan A U R, Huang K, Khalaji M S, et al. Multifunctional bioactive core-shell electrospun membrane capable to terminate inflammatory cycle and promote angiogenesis in diabetic wound. Bioactive Materials, 2021, 6(9): 2783-2800.
doi: 10.1016/j.bioactmat.2021.01.040 pmid: 33665509
[69] Wang J, Lin J W, Chen L, et al. Endogenous electric-field-coupled electrospun short fiber via collecting wound exudation. Advanced Materials (Deerfield Beach, Fla), 2022, 34(9): e2108325.
[70] Almukainzi M, El-Masry T A, Negm W A, et al. Co-delivery of gentiopicroside and thymoquinone using electrospun m-PEG/PVP nanofibers: In vitro and in vivo studies for antibacterial wound dressing in diabetic rats. International Journal of Pharmaceutics, 2022, 625: 122106.
doi: 10.1016/j.ijpharm.2022.122106
[71] Liu Y H, Zhu T H, Li J, et al. Magnolol hybrid nanofibrous mat with antibacterial, anti-inflammatory, and microvascularized properties for wound treatment. Biomacromolecules, 2022, 23(3): 1124-1137.
doi: 10.1021/acs.biomac.1c01430
[72] Liu F G, Li X Z, Wang L, et al. Sesamol incorporated cellulose acetate-zein composite nanofiber membrane: an efficient strategy to accelerate diabetic wound healing. International Journal of Biological Macromolecules, 2020, 149: 627-638.
doi: S0141-8130(19)38116-4 pmid: 32004602
[1] 袁小晶,尹海梦,樊晓玮,何俊林,郝石磊,季金苟. 角蛋白/海藻酸钠/聚丙烯酰胺水凝胶皮肤敷料的制备及创口修复研究[J]. 中国生物工程杂志, 2021, 41(8): 17-24.
[2] 宋奕,张翠云,李奕,张素素,潘舜,陶云云,许璐摇,何华成,吴疆. 利用静电纺丝技术制备聚己内酯-胶原复合包载碱性成纤维细胞生长因子手术缝纫线及其缓释性能的研究 *[J]. 中国生物工程杂志, 2019, 39(1): 55-62.