Advances and perspective on animal models and hydrogel biomaterials for diabetic wound healing

doi:10.12336/biomatertransl.2022.03.003

Biomaterials Translational ›› 2022, Vol. 3 ›› Issue (3): 188-200.doi: 10.12336/biomatertransl.2022.03.003

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Advances and perspective on animal models and hydrogel biomaterials for diabetic wound healing

Yiqiang Hu¹^,^2,#, Yuan Xiong¹^,^2,#, Ranyang Tao¹^,², Hang Xue¹^,², Lang Chen¹^,², Ze Lin¹^,², Adriana C. Panayi³, Bobin Mi¹^,²^,^*(), Guohui Liu¹^,²^,^*()

1 Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
2 Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, Hubei Province, China
3 Department of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Received:2022-05-01 Revised:2022-05-27 Accepted:2022-08-26 Online:2022-09-28 Published:2022-09-28
Contact: Bobin Mi, E-mail:mibobin@hust.edu.cn; Guohui Liu, liuguohui@hust.edu.cn
About author:Bobin Mi, mibobin@hust.edu.cn;
Guohui Liu, liuguohui@hust.edu.cn.
#Author equally.

Abstract

Abstract:

Diabetic wounds are a common complication in diabetes patients. Due to peripheral nerve damage and vascular dysfunction, diabetic wounds are prone to progress to local ulcers, wound gangrene and even to require amputation, bringing huge psychological and economic burdens to patients. However, the current treatment methods for diabetic wounds mainly include wound accessories, negative pressure drainage, skin grafting and surgery; there is still no ideal treatment to promote diabetic wound healing at present. Appropriate animal models can simulate the physiological mechanism of diabetic wounds, providing a basis for translational research in treating diabetic wound healing. Although there are no animal models that can fully mimic the pathophysiological mechanisms of diabetic wounds in humans, it is vital to explore animal simulation models used in basic research and preclinical studies of diabetic wounds. In addition, hydrogel materials are regarded as a promising treatment for diabetic wounds because of their good antimicrobial activity, biocompatibility, biodegradation and appropriate mechanical properties. Herein, we review and discuss the different animal models used to investigate the pathological mechanisms of diabetic wounds. We further discuss the promising future application of hydrogel biomaterials in diabetic wound healing.

Key words: animal models, diabetic wound, hydrogel biomaterials, pathomechanism

Cite this article

Figures/Tables 3

Figure 1. Diabetic wound models are induced in different animals. DFU: diabetic foot ulcers; HFD: high fat diet; STZ: streptozotocin.

Figure 2. The main factors that contribute to the formation of a diabetic wound. AGE: advanced glycation end products; DFU: diabetic foot ulcers; IL–6: interleukin 6; NF–κB: nuclear factor kappa–B; NO: nitric oxide; ROS: reactive oxygen species; TNF–α: tumour necrosis factor–α.

Figure 3. The current gold standard treatments for diabetic foot ulcers.

References 139

1.	Gandhi, G. Y.; Mooradian, A. D. Management of hyperglycemia in older adults with type 2 diabetes. Drugs Aging. 2022, 39, 39-58. doi: 10.1007/s40266-021-00910-1 URL
2.	Graves, L. E.; Donaghue, K. C. Vascular complication in adolescents with diabetes mellitus. Front Endocrinol (Lausanne). 2020, 11, 370. doi: 10.3389/fendo.2020.00370 URL
3.	Wan, G.; Chen, Y.; Chen, J.; Yan, C.; Wang, C.; Li, W.; Mao, R.; Machens, H. G.; Yang, X.; Chen, Z. Regulation of endothelial progenitor cell functions during hyperglycemia: new therapeutic targets in diabetic wound healing. J Mol Med (Berl). 2022, 100, 485-498. doi: 10.1007/s00109-021-02172-1 URL
4.	den Dekker, A.; Davis, F. M.; Kunkel, S. L.; Gallagher, K. A. Targeting epigenetic mechanisms in diabetic wound healing. Transl Res. 2019, 204, 39-50. doi: 10.1016/j.trsl.2018.10.001 URL
5.	Vijayakumar, V.; Samal, S. K.; Mohanty, S.; Nayak, S. K. Recent advancements in biopolymer and metal nanoparticle-based materials in diabetic wound healing management. Int J Biol Macromol. 2019, 122, 137-148. doi: 10.1016/j.ijbiomac.2018.10.120 URL
6.	Phang, S. J.; Arumugam, B.; Kuppusamy, U. R.; Fauzi, M. B.; Looi, M. L. A review of diabetic wound models-Novel insights into diabetic foot ulcer. J Tissue Eng Regen Med. 2021, 15, 1051-1068. doi: 10.1002/term.3246 URL
7.	Nowak, N. C.; Menichella, D. M.; Miller, R.; Paller, A. S. Cutaneous innervation in impaired diabetic wound healing. Transl Res. 2021, 236, 87-108. doi: 10.1016/j.trsl.2021.05.003 URL
8.	Greenhalgh, D. G. Wound healing and diabetes mellitus. Clin Plast Surg. 2003, 30, 37-45. doi: 10.1016/S0094-1298(02)00066-4 URL
9.	Wang, C.; Guo, M.; Zhang, N.; Wang, G. Effectiveness of honey dressing in the treatment of diabetic foot ulcers: A systematic review and meta-analysis. Complement Ther Clin Pract. 2019, 34, 123-131. doi: 10.1016/j.ctcp.2018.09.004 URL
10.	Khamaisi, M.; Balanson, S. Dysregulation of wound healing mechanisms in diabetes and the importance of negative pressure wound therapy (NPWT). Diabetes Metab Res Rev. 2017, 33, e2929.
11.	Gurtner, G. C.; Werner, S.; Barrandon, Y.; Longaker, M. T. Wound repair and regeneration. Nature. 2008, 453, 314-321. doi: 10.1038/nature07039 URL
12.	Nourian Dehkordi, A.; Mirahmadi Babaheydari, F.; Chehelgerdi, M.; Raeisi Dehkordi, S. Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies. Stem Cell Res Ther. 2019, 10, 111. doi: 10.1186/s13287-019-1212-2 URL
13.	Dekoninck, S.; Blanpain, C. Stem cell dynamics, migration and plasticity during wound healing. Nat Cell Biol. 2019, 21, 18-24. doi: 10.1038/s41556-018-0237-6 URL
14.	Yang, F.; Bai, X.; Dai, X.; Li, Y. The biological processes during wound healing. Regen Med. 2021, 16, 373-390. doi: 10.2217/rme-2020-0066 URL
15.	Moura, L. I.; Dias, A. M.; Carvalho, E.; de Sousa, H. C. Recent advances on the development of wound dressings for diabetic foot ulcer treatment--a review. Acta Biomater. 2013, 9, 7093-7114. doi: 10.1016/j.actbio.2013.03.033 URL
16.	Broughton, G., 2nd; Janis, J. E.; Attinger, C. E. Wound healing: an overview. Plast Reconstr Surg. 2006, 117, 1e-S-32e-S.
17.	Yang, R.; Liu, F.; Wang, J.; Chen, X.; Xie, J.; Xiong, K. Epidermal stem cells in wound healing and their clinical applications. Stem Cell Res Ther. 2019, 10, 229. doi: 10.1186/s13287-019-1312-z URL
18.	Han, G.; Ceilley, R. Chronic wound healing: a review of current management and treatments. Adv Ther. 2017, 34, 599-610. doi: 10.1007/s12325-017-0478-y URL
19.	Rani, S.; Ritter, T. The exosome - a naturally secreted nanoparticle and its application to wound healing. Adv Mater. 2016, 28, 5542-5552. doi: 10.1002/adma.201504009 URL
20.	Rai, V.; Moellmer, R.; Agrawal, D. K. Clinically relevant experimental rodent models of diabetic foot ulcer. Mol Cell Biochem. 2022, 477, 1239-1247. doi: 10.1007/s11010-022-04372-w URL
21.	Goyal, S. N.; Reddy, N. M.; Patil, K. R.; Nakhate, K. T.; Ojha, S.; Patil, C. R.; Agrawal, Y. O. Challenges and issues with streptozotocin-induced diabetes - A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chem Biol Interact. 2016, 244, 49-63. doi: 10.1016/j.cbi.2015.11.032 URL
22.	Ansell, D. M.; Marsh, C.; Walker, L.; Hardman, M. J.; Holden, K. Evaluating STZ-induced impaired wound healing in rats. J Invest Dermatol. 2018, 138, 994-997.
23.	Yu, M.; Liu, W.; Li, J.; Lu, J.; Lu, H.; Jia, W.; Liu, F. Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway. Stem Cell Res Ther. 2020, 11, 350. doi: 10.1186/s13287-020-01824-2 URL
24.	Szkudelski, T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med (Maywood). 2012, 237, 481-490. doi: 10.1258/ebm.2012.011372 URL
25.	Ahmed, R.; Afreen, A.; Tariq, M.; Zahid, A. A.; Masoud, M. S.; Ahmed, M.; Ali, I.; Akram, Z.; Hasan, A. Bone marrow mesenchymal stem cells preconditioned with nitric-oxide-releasing chitosan/PVA hydrogel accelerate diabetic wound healing in rabbits. Biomed Mater. 2021, 16, 035014. doi: 10.1088/1748-605X/abc28b URL
26.	Malone-Povolny, M. J.; Maloney, S. E.; Schoenfisch, M. H. Nitric oxide therapy for diabetic wound healing. Adv Healthc Mater. 2019, 8, e1801210.
27.	Hoppenbrouwers, T.; Tuk, B.; Fijneman, E. M.; de Maat, M. P.; van Neck, J. W. Fibrin improves skin wound perfusion in a diabetic rat model. Thromb Res. 2017, 151, 36-40. doi: 10.1016/j.thromres.2017.01.002 URL
28.	Kaymakcalan, O. E.; Abadeer, A.; Goldufsky, J. W.; Galili, U.; Karinja, S. J.; Dong, X.; Jin, J. L.; Samadi, A.; Spector, J. A. Topical α-gal nanoparticles accelerate diabetic wound healing. Exp Dermatol. 2020, 29, 404-413. doi: 10.1111/exd.14084 URL
29.	Dunn, L.; Prosser, H. C.; Tan, J. T.; Vanags, L. Z.; Ng, M. K.; Bursill, C. A. Murine model of wound healing. J Vis Exp. 2013, e50265.
30.	Li, G.; Ko, C. N.; Li, D.; Yang, C.; Wang, W.; Yang, G. J.; Di Primo, C.; Wong, V. K. W.; Xiang, Y.; Lin, L.; Ma, D. L.; Leung, C. H. A small molecule HIF-1α stabilizer that accelerates diabetic wound healing. Nat Commun. 2021, 12, 3363. doi: 10.1038/s41467-021-23448-7 URL
31.	King, A. J. The use of animal models in diabetes research. Br J Pharmacol. 2012, 166, 877-894. doi: 10.1111/j.1476-5381.2012.01911.x URL
32.	Yang, J.; Chen, Z.; Pan, D.; Li, H.; Shen, J. Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration. Int J Nanomedicine. 2020, 15, 5911-5926. doi: 10.2147/IJN.S249129 URL
33.	Zhang, J.; Zhou, R.; Xiang, C.; Jia, Q.; Wu, H.; Yang, H. Huangbai Liniment accelerated wound healing by activating Nrf2 signaling in diabetes. Oxid Med Cell Longev. 2020, 2020, 4951820.
34.	Liu, W.; Yu, M.; Xie, D.; Wang, L.; Ye, C.; Zhu, Q.; Liu, F.; Yang, L. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res Ther. 2020, 11, 259. doi: 10.1186/s13287-020-01756-x URL
35.	Abo El-Magd, N. F.; Ramadan, N. M.; Eraky, S. M. The ameliorative effect of bromelain on STZ-induced type 1 diabetes in rats through Oxi-LDL/LPA/LPAR1 pathway. Life Sci. 2021, 285, 119982. doi: 10.1016/j.lfs.2021.119982 URL
36.	Jayasimhan, A.; Mansour, K. P.; Slattery, R. M. Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse. Clin Sci (Lond). 2014, 126, 1-18. doi: 10.1042/CS20120627 URL
37.	Driver, J. P.; Serreze, D. V.; Chen, Y. G. Mouse models for the study of autoimmune type 1 diabetes: a NOD to similarities and differences to human disease. Semin Immunopathol. 2011, 33, 67-87. doi: 10.1007/s00281-010-0204-1 URL
38.	Giarratana, N.; Penna, G.; Adorini, L. Animal models of spontaneous autoimmune disease: type 1 diabetes in the nonobese diabetic mouse. Methods Mol Biol. 2007, 380, 285-311.
39.	Irvin, A. E.; Jhala, G.; Zhao, Y.; Blackwell, T. S.; Krishnamurthy, B.; Thomas, H. E.; Kay, T. W. H. NF-κB is weakly activated in the NOD mouse model of type 1 diabetes. Sci Rep. 2018, 8, 4217. doi: 10.1038/s41598-018-22738-3 URL
40.	Jiang, Y.; Xie, F.; Lv, X.; Wang, S.; Liao, X.; Yu, Y.; Dai, Q.; Zhang, Y.; Meng, J.; Hu, G.; Peng, Z.; Tao, L. Mefunidone ameliorates diabetic kidney disease in STZ and db/db mice. FASEB J. 2021, 35, e21198.
41.	Wang, M.; Song, L.; Strange, C.; Dong, X.; Wang, H. Therapeutic effects of adipose stem cells from diabetic mice for the treatment of type 2 diabetes. Mol Ther. 2018, 26, 1921-1930. doi: 10.1016/j.ymthe.2018.06.013 URL
42.	Sakai, S.; Yamamoto, T.; Takabatake, Y.; Takahashi, A.; Namba-Hamano, T.; Minami, S.; Fujimura, R.; Yonishi, H.; Matsuda, J.; Hesaka, A.; Matsui, I.; Matsusaka, T.; Niimura, F.; Yanagita, M.; Isaka, Y. Proximal tubule autophagy differs in type 1 and 2 diabetes. J Am Soc Nephrol. 2019, 30, 929-945. doi: 10.1681/ASN.2018100983 URL
43.	Heydemann, A. An overview of murine high fat diet as a model for type 2 diabetes mellitus. J Diabetes Res. 2016, 2016, 2902351.
44.	Silamiķele, L.; Silamiķelis, I.; Ustinova, M.; Kalniņa, Z.; Elbere, I.; Petrovska, R.; Kalniņa, I.; Kloviņš, J. Metformin strongly affects gut microbiome composition in high-fat diet-induced type 2 diabetes mouse model of both sexes. Front Endocrinol (Lausanne). 2021, 12, 626359. doi: 10.3389/fendo.2021.626359 URL
45.	Grada, A.; Mervis, J.; Falanga, V. Research techniques made simple: animal models of wound healing. J Invest Dermatol. 2018, 138:2095-2105.e1. doi: 10.1016/j.jid.2018.08.005 URL
46.	Saleem Mir, M.; Maqbool Darzi, M.; Khalil Baba, O.; Khan, H. M.; Kamil, S. A.; Sofi, A. H.; Wani, S. A. Streptozotocin induced acute clinical effects in rabbits (Oryctolagus cuniculus). Iran J Pathol. 2015, 10, 206-213.
47.	Conaway, H. H.; Faas, F. H.; Smith, S. D.; Sanders, L. L. Spontaneous diabetes mellitus in the New Zealand white rabbit: physiologic characteristics. Metabolism. 1981, 30, 50-56. doi: 10.1016/0026-0495(81)90218-3 URL
48.	Zhang, J.; Hu, W.; Diao, Q.; Wang, Z.; Miao, J.; Chen, X.; Xue, Z. Therapeutic effect of the epidermal growth factor on diabetic foot ulcer and the underlying mechanisms. Exp Ther Med. 2019, 17, 1643-1648.
49.	O’Loughlin, A.; Kulkarni, M.; Vaughan, E. E.; Creane, M.; Liew, A.; Dockery, P.; Pandit, A.; O’Brien, T. Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model. Stem Cell Res Ther. 2013, 4, 158. doi: 10.1186/scrt388 URL
50.	O’Loughlin, A.; Kulkarni, M.; Creane, M.; Vaughan, E. E.; Mooney, E.; Shaw, G.; Murphy, M.; Dockery, P.; Pandit, A.; O’Brien, T. Topical administration of allogeneic mesenchymal stromal cells seeded in a collagen scaffold augments wound healing and increases angiogenesis in the diabetic rabbit ulcer. Diabetes. 2013, 62, 2588-2594. doi: 10.2337/db12-1822 URL
51.	Velander, P.; Theopold, C.; Hirsch, T.; Bleiziffer, O.; Zuhaili, B.; Fossum, M.; Hoeller, D.; Gheerardyn, R.; Chen, M.; Visovatti, S.; Svensson, H.; Yao, F.; Eriksson, E. Impaired wound healing in an acute diabetic pig model and the effects of local hyperglycemia. Wound Repair Regen. 2008, 16, 288-293. doi: 10.1111/j.1524-475X.2008.00367.x URL
52.	Ramirez, H. A.; Pastar, I.; Jozic, I.; Stojadinovic, O.; Stone, R. C.; Ojeh, N.; Gil, J.; Davis, S. C.; Kirsner, R. S.; Tomic-Canic, M. Staphylococcus aureus triggers induction of miR-15B-5P to Diminish DNA repair and deregulate inflammatory response in diabetic foot ulcers. J Invest Dermatol. 2018, 138, 1187-1196. doi: 10.1016/j.jid.2017.11.038 URL
53.	Sawaya, A. P.; Jozic, I.; Stone, R. C.; Pastar, I.; Egger, A. N.; Stojadinovic, O.; Glinos, G. D.; Kirsner, R. S.; Tomic-Canic, M. Mevastatin promotes healing by targeting caveolin-1 to restore EGFR signaling. JCI Insight. 2019, 4, e129320.
54.	Podell, B. K.; Ackart, D. F.; Richardson, M. A.; DiLisio, J. E.; Pulford, B.; Basaraba, R. J. A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment. Dis Model Mech. 2017, 10, 151-162.
55.	Verhagen, J.; Smith, E. L.; Whettlock, E. M.; Macintyre, B.; Peakman, M. Proinsulin-mediated induction of type 1 diabetes in HLA-DR4-transgenic mice. Sci Rep. 2018, 8, 14106. doi: 10.1038/s41598-018-32546-4 URL
56.	Perez-Favila, A.; Martinez-Fierro, M. L.; Rodriguez-Lazalde, J. G.; Cid-Baez, M. A.; Zamudio-Osuna, M. J.; Martinez-Blanco, M. D. R.; Mollinedo-Montaño, F. E.; Rodriguez-Sanchez, I. P.; Castañeda-Miranda, R.; Garza-Veloz, I. Current therapeutic strategies in diabetic foot ulcers. Medicina (Kaunas). 2019, 55, 714.
57.	Dixon, D.; Edmonds, M. Managing diabetic foot ulcers: pharmacotherapy for wound healing. Drugs. 2021, 81, 29-56. doi: 10.1007/s40265-020-01415-8 URL
58.	Reardon, R.; Simring, D.; Kim, B.; Mortensen, J.; Williams, D.; Leslie, A. The diabetic foot ulcer. Aust J Gen Pract. 2020, 49, 250-255. doi: 10.31128/AJGP-11-19-5161 URL
59.	Lim, J. Z.; Ng, N. S.; Thomas, C. Prevention and treatment of diabetic foot ulcers. J R Soc Med. 2017, 110, 104-109. doi: 10.1177/0141076816688346 URL
60.	American Diabetes Association. 11. Microvascular complications and foot care: standards of medical care in diabetes-2020. Diabetes Care. 2020, 43, S135-S151.
61.	Migdalis, I.; Czupryniak, L.; Lalic, N.; Leslie, R. D.; Papanas, N.; Valensi, P. Diabetic microvascular complications. Int J Endocrinol. 2018, 2018, 5683287.
62.	Strain, W. D.; Paldánius, P. M. Diabetes, cardiovascular disease and the microcirculation. Cardiovasc Diabetol. 2018, 17, 57. doi: 10.1186/s12933-018-0703-2 URL
63.	Forbes, J. M.; Cooper, M. E. Mechanisms of diabetic complications. Physiol Rev. 2013, 93, 137-188. doi: 10.1152/physrev.00045.2011 URL
64.	Alicic, R. Z.; Rooney, M. T.; Tuttle, K. R. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017, 12, 2032-2045. doi: 10.2215/CJN.11491116 URL
65.	Ricciardi, C. A.; Gnudi, L. Kidney disease in diabetes: from mechanisms to clinical presentation and treatment strategies. Metabolism. 2021, 124, 154890. doi: 10.1016/j.metabol.2021.154890 URL
66.	Schoina, M.; Loutradis, C.; Theodorakopoulou, M.; Dimitroulas, T.; Triantafillidou, E.; Doumas, M.; Karagiannis, A.; Garyfallos, A.; Papagianni, A.; Sarafidis, P. The presence of diabetes mellitus further impairs structural and functional capillary density in patients with chronic kidney disease. Microcirculation. 2021, 28, e12665.
67.	Sabanayagam, C.; Banu, R.; Chee, M. L.; Lee, R.; Wang, Y. X.; Tan, G.; Jonas, J. B.; Lamoureux, E. L.; Cheng, C. Y.; Klein, B. E. K.; Mitchell, P.; Klein, R.; Cheung, C. M. G.; Wong, T. Y. Incidence and progression of diabetic retinopathy: a systematic review. Lancet Diabetes Endocrinol. 2019, 7, 140-149. doi: 10.1016/S2213-8587(18)30128-1 URL
68.	Wu, L.; Gunton, J. E. The Changing landscape of pharmacotherapy for diabetes mellitus: a review of cardiovascular outcomes. Int J Mol Sci. 2019, 20, 5853. doi: 10.3390/ijms20235853 URL
69.	Low Wang, C. C.; Everett, B. M.; Burman, K. D.; Wilson, P. W. F. Cardiovascular safety trials for all new diabetes mellitus drugs? Circulation. 2019, 139, 1741-1743. doi: 10.1161/CIRCULATIONAHA.118.038771 URL
70.	Apelqvist, J. A.; Lepäntalo, M. J. The ulcerated leg: when to revascularize. Diabetes Metab Res Rev. 2012, 28 Suppl 1, 30-35.
71.	Korzon-Burakowska, A.; Edmonds, M. Role of the microcirculation in diabetic foot ulceration. Int J Low Extrem Wounds. 2006, 5, 144-148. doi: 10.1177/1534734606292037 URL
72.	Grennan, D. Diabetic foot ulcers. JAMA. 2019, 321, 114. doi: 10.1001/jama.2018.18323 URL
73.	Chao, C. Y.; Cheing, G. L. Microvascular dysfunction in diabetic foot disease and ulceration. Diabetes Metab Res Rev. 2009, 25, 604-614. doi: 10.1002/dmrr.1004 URL
74.	Volmer-Thole, M.; Lobmann, R. Neuropathy and diabetic foot syndrome. Int J Mol Sci. 2016, 17, 917. doi: 10.3390/ijms17060917 URL
75.	Hicks, C. W.; Selvin, E. Epidemiology of peripheral neuropathy and lower extremity disease in diabetes. Curr Diab Rep. 2019, 19, 86. doi: 10.1007/s11892-019-1212-8 URL
76.	Balasubramanian, G.; Vas, P.; Chockalingam, N.; Naemi, R. A synoptic overview of neurovascular interactions in the foot. Front Endocrinol (Lausanne). 2020, 11, 308. doi: 10.3389/fendo.2020.00308 URL
77.	Lechleitner, M.; Abrahamian, H.; Francesconi, C.; Kofler, M.; Sturm, W.; Köhler, G. Diabetic neuropathy and diabetic foot syndrome (Update 2019). Wien Klin Wochenschr. 2019, 131, 141-150. doi: 10.1007/s00508-019-1487-4 pmid: 30980143
78.	Lima, A. L.; Illing, T.; Schliemann, S.; Elsner, P. Cutaneous manifestations of diabetes mellitus: a review. Am J Clin Dermatol. 2017, 18, 541-553. doi: 10.1007/s40257-017-0275-z URL
79.	Zilliox, L. A. Diabetes and peripheral nerve disease. Clin Geriatr Med. 2021, 37, 253-267. doi: 10.1016/j.cger.2020.12.001 URL
80.	Zhang, Y.; Lazzarini, P. A.; McPhail, S. M.; van Netten, J. J.; Armstrong, D. G.; Pacella, R. E. Global disability burdens of diabetes-related lower-extremity complications in 1990 and 2016. Diabetes Care. 2020, 43, 964-974. doi: 10.2337/dc19-1614 URL
81.	Yang, H.; Sloan, G.; Ye, Y.; Wang, S.; Duan, B.; Tesfaye, S.; Gao, L. New perspective in diabetic neuropathy: from the periphery to the brain, a call for early detection, and precision medicine. Front Endocrinol (Lausanne). 2019, 10, 929. doi: 10.3389/fendo.2019.00929 URL
82.	Tuttolomondo, A.; Maida, C.; Pinto, A. Diabetic foot syndrome: immune-inflammatory features as possible cardiovascular markers in diabetes. World J Orthop. 2015, 6, 62-76. doi: 10.5312/wjo.v6.i1.62 URL
83.	Giri, B.; Dey, S.; Das, T.; Sarkar, M.; Banerjee, J.; Dash, S. K. Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: An update on glucose toxicity. Biomed Pharmacother. 2018, 107, 306-328. doi: 10.1016/j.biopha.2018.07.157 URL
84.	Davis, F. M.; Kimball, A.; Boniakowski, A.; Gallagher, K. Dysfunctional wound healing in diabetic foot ulcers: new crossroads. Curr Diab Rep. 2018, 18, 2. doi: 10.1007/s11892-018-0970-z URL
85.	Gardner, S. E.; Frantz, R. A. Wound bioburden and infection-related complications in diabetic foot ulcers. Biol Res Nurs. 2008, 10, 44-53. doi: 10.1177/1099800408319056 URL
86.	Adeghate, J.; Nurulain, S.; Tekes, K.; Fehér, E.; Kalász, H.; Adeghate, E. Novel biological therapies for the treatment of diabetic foot ulcers. Expert Opin Biol Ther. 2017, 17, 979-987. doi: 10.1080/14712598.2017.1333596 URL
87.	Pitocco, D.; Spanu, T.; Di Leo, M.; Vitiello, R.; Rizzi, A.; Tartaglione, L.; Fiori, B.; Caputo, S.; Tinelli, G.; Zaccardi, F.; Flex, A.; Galli, M.; Pontecorvi, A.; Sanguinetti, M. Diabetic foot infections: a comprehensive overview. Eur Rev Med Pharmacol Sci. 2019, 23, 26-37.
88.	Ghotaslou, R.; Memar, M. Y.; Alizadeh, N. Classification, microbiology and treatment of diabetic foot infections. J Wound Care. 2018, 27, 434-441. doi: 10.12968/jowc.2018.27.7.434 URL
89.	Dumville, J. C.; Lipsky, B. A.; Hoey, C.; Cruciani, M.; Fiscon, M.; Xia, J. Topical antimicrobial agents for treating foot ulcers in people with diabetes. Cochrane Database Syst Rev. 2017, 6, CD011038.
90.	Everett, E.; Mathioudakis, N. Update on management of diabetic foot ulcers. Ann N Y Acad Sci. 2018, 1411, 153-165. doi: 10.1111/nyas.13569 URL
91.	Alavi, A.; Sibbald, R. G.; Mayer, D.; Goodman, L.; Botros, M.; Armstrong, D. G.; Woo, K.; Boeni, T.; Ayello, E. A.; Kirsner, R. S. Diabetic foot ulcers: Part I. Pathophysiology and prevention. J Am Acad Dermatol. 2014, 70, 1.e1-18; quiz 19-20. doi: 10.1016/j.jaad.2013.08.019 URL
92.	Aldana, P. C.; Khachemoune, A. Diabetic foot ulcers: appraising standard of care and reviewing new trends in management. Am J Clin Dermatol. 2020, 21, 255-264. doi: 10.1007/s40257-019-00495-x URL
93.	Lebrun, E.; Tomic-Canic, M.; Kirsner, R. S. The role of surgical debridement in healing of diabetic foot ulcers. Wound Repair Regen. 2010, 18, 433-438. doi: 10.1111/j.1524-475X.2010.00619.x URL
94.	Edwards, J.; Stapley, S. Debridement of diabetic foot ulcers. Cochrane Database Syst Rev. 2010, 2010, CD003556.
95.	Alexiadou, K.; Doupis, J. Management of diabetic foot ulcers. Diabetes Ther. 2012, 3, 4. doi: 10.1007/s13300-012-0004-9 URL
96.	Patry, J.; Blanchette, V. Enzymatic debridement with collagenase in wounds and ulcers: a systematic review and meta-analysis. Int Wound J. 2017, 14, 1055-1065. doi: 10.1111/iwj.12760 URL
97.	Singh, N.; Armstrong, D. G.; Lipsky, B. A. Preventing foot ulcers in patients with diabetes. JAMA. 2005, 293, 217-228. doi: 10.1001/jama.293.2.217 URL
98.	Sen, P.; Demirdal, T.; Emir, B. Meta-analysis of risk factors for amputation in diabetic foot infections. Diabetes Metab Res Rev. 2019, 35, e3165.
99.	Macdonald, K. E.; Boeckh, S.; Stacey, H. J.; Jones, J. D. The microbiology of diabetic foot infections: a meta-analysis. BMC Infect Dis. 2021, 21, 770. doi: 10.1186/s12879-021-06516-7 URL
100.	Barwell, N. D.; Devers, M. C.; Kennon, B.; Hopkinson, H. E.; McDougall, C.; Young, M. J.; Robertson, H. M. A.; Stang, D.; Dancer, S. J.; Seaton, A.; Leese, G. P.; Scottish Diabetes Foot Action Group. Diabetic foot infection: Antibiotic therapy and good practice recommendations. Int J Clin Pract. 2017, 71, e13006.
101.	Lipsky, B. A.; Berendt, A. R.; Cornia, P. B.; Pile, J. C.; Peters, E. J.; Armstrong, D. G.; Deery, H. G.; Embil, J. M.; Joseph, W. S.; Karchmer, A. W.; Pinzur, M. S.; Senneville, E.; Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012, 54, e132-173. doi: 10.1093/cid/cis346 URL
102.	Lipsky, B. A.; Berendt, A. R.; Cornia, P. B.; Pile, J. C.; Peters, E. J.; Armstrong, D. G.; Deery, H. G.; Embil, J. M.; Joseph, W. S.; Karchmer, A. W.; Pinzur, M. S.; Senneville, E.; Infectious Diseases Society of America. Executive summary: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012, 54, 1679-1684. doi: 10.1093/cid/cis460 URL
103.	Cavanagh, P. R.; Ulbrecht, J. S.; Caputo, G. M. New developments in the biomechanics of the diabetic foot. Diabetes Metab Res Rev. 2000, 16 Suppl 1, S6-S10.
104.	Ahluwalia, R.; Maffulli, N.; Lázaro-Martínez, J. L.; Kirketerp-Møller, K.; Reichert, I. Diabetic foot off loading and ulcer remission: Exploring surgical off-loading. Surgeon. 2021, 19, e526-e535.
105.	Zwaferink, J. B. J.; Custers, W.; Paardekooper, I.; Berendsen, H. A.; Bus, S. A. Optimizing footwear for the diabetic foot: Data-driven custom-made footwear concepts and their effect on pressure relief to prevent diabetic foot ulceration. PLoS One. 2020, 15, e0224010.
106.	Bus, S. A. Foot structure and footwear prescription in diabetes mellitus. Diabetes Metab Res Rev. 2008, 24 Suppl 1, S90-95.
107.	Peter-Riesch, B. The diabetic foot: The never-ending challenge. Endocr Dev. 2016, 31, 108-134.
108.	Mavrogenis, A. F.; Megaloikonomos, P. D.; Antoniadou, T.; Igoumenou, V. G.; Panagopoulos, G. N.; Dimopoulos, L.; Moulakakis, K. G.; Sfyroeras, G. S.; Lazaris, A. Current concepts for the evaluation and management of diabetic foot ulcers. EFORT Open Rev. 2018, 3, 513-525. doi: 10.1302/2058-5241.3.180010 URL
109.	Caetano, A. P.; Conde Vasco, I.; Veloso Gomes, F.; Costa, N. V.; Luz, J. H.; Spaepen, E.; Formiga, A.; Coimbra, É.; Neves, J.; Bilhim, T. Successful revascularization has a significant impact on limb salvage rate and wound healing for patients with diabetic foot ulcers: single-centre retrospective analysis with a multidisciplinary approach. Cardiovasc Intervent Radiol. 2020, 43, 1449-1459. doi: 10.1007/s00270-020-02604-4 URL
110.	Hinchliffe, R. J.; Brownrigg, J. R.; Andros, G.; Apelqvist, J.; Boyko, E. J.; Fitridge, R.; Mills, J. L.; Reekers, J.; Shearman, C. P.; Zierler, R. E.; Schaper, N. C.; International Working Group on the Diabetic Foot. Effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral artery disease: a systematic review. Diabetes Metab Res Rev. 2016, 32 Suppl 1, 136-144.
111.	Hicks, C. W.; Canner, J. K.; Sherman, R. L.; Black, J. H., 3rd; Lum, Y. W.; Abularrage, C. J. Evaluation of revascularization benefit quartiles using the Wound, Ischemia, and foot Infection classification system for diabetic patients with chronic limb-threatening ischemia. J Vasc Surg. 2021, 74, 1232-1239.e3. doi: 10.1016/j.jvs.2021.03.017 URL
112.	Causey, M. W.; Ahmed, A.; Wu, B.; Gasper, W. J.; Reyzelman, A.; Vartanian, S. M.; Hiramoto, J. S.; Conte, M. S. Society for Vascular Surgery limb stage and patient risk correlate with outcomes in an amputation prevention program. J Vasc Surg. 2016, 63, 1563-1573.e2. doi: 10.1016/j.jvs.2016.01.011 URL
113.	Baltzis, D.; Eleftheriadou, I.; Veves, A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther. 2014, 31, 817-836. doi: 10.1007/s12325-014-0140-x URL
114.	Vatankhah, N.; Jahangiri, Y.; Landry, G. J.; Moneta, G. L.; Azarbal, A. F. Effect of systemic insulin treatment on diabetic wound healing. Wound Repair Regen. 2017, 25, 288-291. doi: 10.1111/wrr.12514 URL
115.	Fan, H. J.; Yu, J. H.; Cui, G. M.; Zhang, W. Y.; Yang, X.; Dong, Q. J. Insulin pump for the treatment of diabetes in combination with ulcerative foot infections. J Biol Regul Homeost Agents. 2016, 30, 465-470.
116.	Lima, M. H.; Caricilli, A. M.; de Abreu, L. L.; Araújo, E. P.; Pelegrinelli, F. F.; Thirone, A. C.; Tsukumo, D. M.; Pessoa, A. F.; dos Santos, M. F.; de Moraes, M. A.; Carvalheira, J. B.; Velloso, L. A.; Saad, M. J. Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways: a double-blind placebo-controlled clinical trial. PLoS One. 2012, 7, e36974.
117.	Sun, Y.; Fan, W.; Yang, W.; Wang, G.; Yu, G.; Zhang, D.; Wang, Y. Effects of intermittent irrigation of insulin solution combined with continuous drainage of vacuum sealing drainage in chronic diabetic lower limb ulcers. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2015, 29, 812-817.
118.	Saboo, A.; Rathnayake, A.; Vangaveti, V. N.; Malabu, U. H. Wound healing effects of dipeptidyl peptidase-4 inhibitors: An emerging concept in management of diabetic foot ulcer-A review. Diabetes Metab Syndr. 2016, 10, 113-119. doi: 10.1016/j.dsx.2015.04.006 URL
119.	Zolali, E.; Rezabakhsh, A.; Nabat, E.; Jaberi, H.; Rahbarghazi, R.; Garjani, A. Metformin effect on endocan biogenesis in human endothelial cells under diabetic condition. Arch Med Res. 2019, 50, 304-314.
120.	Seo, E.; Lim, J. S.; Jun, J. B.; Choi, W.; Hong, I. S.; Jun, H. S. Exendin-4 in combination with adipose-derived stem cells promotes angiogenesis and improves diabetic wound healing. J Transl Med. 2017, 15, 35. doi: 10.1186/s12967-017-1145-4 URL
121.	Zhang, L.; Ma, Y.; Pan, X.; Chen, S.; Zhuang, H.; Wang, S. A composite hydrogel of chitosan/heparin/poly (γ-glutamic acid) loaded with superoxide dismutase for wound healing. Carbohydr Polym. 2018, 180, 168-174. doi: 10.1016/j.carbpol.2017.10.036 URL
122.	Gong, C.; Wu, Q.; Wang, Y.; Zhang, D.; Luo, F.; Zhao, X.; Wei, Y.; Qian, Z. A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials. 2013, 34, 6377-6387. doi: 10.1016/j.biomaterials.2013.05.005 URL
123.	Ma, H.; Zhou, Q.; Chang, J.; Wu, C. Grape seed-inspired smart hydrogel scaffolds for melanoma therapy and wound healing. ACS Nano. 2019, 13, 4302-4311. doi: 10.1021/acsnano.8b09496 URL
124.	Mao, C.; Xiang, Y.; Liu, X.; Cui, Z.; Yang, X.; Yeung, K. W. K.; Pan, H.; Wang, X.; Chu, P. K.; Wu, S. Photo-inspired antibacterial activity and wound healing acceleration by hydrogel embedded with Ag/Ag@AgCl/ZnO nanostructures. ACS Nano. 2017, 11, 9010-9021. doi: 10.1021/acsnano.7b03513 URL
125.	Eke, G.; Mangir, N.; Hasirci, N.; MacNeil, S.; Hasirci, V. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. Biomaterials. 2017, 129, 188-198. doi: 10.1016/j.biomaterials.2017.03.021 URL
126.	Han, L.; Lu, X.; Wang, M.; Gan, D.; Deng, W.; Wang, K.; Fang, L.; Liu, K.; Chan, C. W.; Tang, Y.; Weng, L. T.; Yuan, H. A mussel-inspired conductive, self-adhesive, and self-healable tough hydrogel as cell stimulators and implantable bioelectronics. Small. 2017, 13, 1601916. doi: 10.1002/smll.201601916 URL
127.	Zhang, K.; Jia, Z.; Yang, B.; Feng, Q.; Xu, X.; Yuan, W.; Li, X.; Chen, X.; Duan, L.; Wang, D.; Bian, L. Adaptable hydrogels mediate cofactor-assisted activation of biomarker-responsive drug delivery via positive feedback for enhanced tissue regeneration. Adv Sci (Weinh). 2018, 5, 1800875.
128.	Wang, M.; Wang, C.; Chen, M.; Xi, Y.; Cheng, W.; Mao, C.; Xu, T.; Zhang, X.; Lin, C.; Gao, W.; Guo, Y.; Lei, B. Efficient angiogenesis-based diabetic wound healing/skin reconstruction through bioactive antibacterial adhesive ultraviolet shielding nanodressing with exosome release. ACS Nano. 2019, 13, 10279-10293. doi: 10.1021/acsnano.9b03656 URL
129.	Shi, Q.; Luo, X.; Huang, Z.; Midgley, A. C.; Wang, B.; Liu, R.; Zhi, D.; Wei, T.; Zhou, X.; Qiao, M.; Zhang, J.; Kong, D.; Wang, K. Cobalt-mediated multi-functional dressings promote bacteria-infected wound healing. Acta Biomater. 2019, 86, 465-479. doi: 10.1016/j.actbio.2018.12.048 URL
130.	Annabi, N.; Rana, D.; Shirzaei Sani, E.; Portillo-Lara, R.; Gifford, J. L.; Fares, M. M.; Mithieux, S. M.; Weiss, A. S. Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing. Biomaterials. 2017, 139, 229-243. doi: 10.1016/j.biomaterials.2017.05.011 URL
131.	Li, L.; Yan, B.; Yang, J.; Chen, L.; Zeng, H. Novel mussel-inspired injectable self-healing hydrogel with anti-biofouling property. Adv Mater. 2015, 27, 1294-1299. doi: 10.1002/adma.201405166 URL
132.	Guo, C.; Wu, Y.; Li, W.; Wang, Y.; Kong, Q. Development of a microenvironment-responsive hydrogel promoting chronically infected diabetic wound healing through sequential hemostatic, antibacterial, and angiogenic activities. ACS Appl Mater Interfaces. 2022, 14, 30480-30492. doi: 10.1021/acsami.2c02725 URL
133.	Hao, Y.; Zhao, W.; Zhang, H.; Zheng, W.; Zhou, Q. Carboxymethyl chitosan-based hydrogels containing fibroblast growth factors for triggering diabetic wound healing. Carbohydr Polym. 2022, 287, 119336. doi: 10.1016/j.carbpol.2022.119336 URL
134.	Xu, Z.; Liu, Y.; Ma, R.; Chen, J.; Qiu, J.; Du, S.; Li, C.; Wu, Z.; Yang, X.; Chen, Z.; Chen, T. Thermosensitive hydrogel incorporating prussian blue nanoparticles promotes diabetic wound healing via ROS scavenging and mitochondrial function restoration. ACS Appl Mater Interfaces. 2022, 14, 14059-14071. doi: 10.1021/acsami.1c24569 URL
135.	Laiva, A. L.; O’Brien, F. J.; Keogh, M. B. Innovations in gene and growth factor delivery systems for diabetic wound healing. J Tissue Eng Regen Med. 2018, 12, e296-e312.
136.	Niu, H.; Li, H.; Guan, Y.; Zhou, X.; Li, Z.; Zhao, S. L.; Chen, P.; Tan, T.; Zhu, H.; Bergdall, V.; Xu, X.; Ma, J.; Guan, J. Sustained delivery of rhMG53 promotes diabetic wound healing and hair follicle development. Bioact Mater. 2022, 18, 104-115.
137.	Lee, Y. H.; Lin, S. J. Chitosan/PVA hetero-composite hydrogel containing antimicrobials, perfluorocarbon nanoemulsions, and growth factor-loaded nanoparticles as a multifunctional dressing for diabetic wound healing: synthesis, characterization, and in vitro/in vivo evaluation. Pharmaceutics. 2022, 14: 537. doi: 10.3390/pharmaceutics14030537 URL
138.	Wu, C.; Long, L.; Zhang, Y.; Xu, Y.; Lu, Y.; Yang, Z.; Guo, Y.; Zhang, J.; Hu, X.; Wang, Y. Injectable conductive and angiogenic hydrogels for chronic diabetic wound treatment. J Control Release. 2022, 344, 249-260. doi: 10.1016/j.jconrel.2022.03.014 URL
139.	Hu, Y.; Wu, B.; Xiong, Y.; Tao, R.; Panayi, A. C.; Chen, L.; Tian, W.; Xue, H.; Shi, L.; Zhang, X.; Xiong, L.; Mi, B.; Liu, G. Cryogenic 3D printed hydrogel scaffolds loading exosomes accelerate diabetic wound healing. Chem Eng J. 2021, 426, 130634. doi: 10.1016/j.cej.2021.130634 URL

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