Login Register Cart 0
Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Diabetic Wound: Pathophysiology, Complications and Treatment Strategies

Author(s): Sunita Chauhan, Monika Gulia, Rahul Pratap Singh and Vikas Jhawat*

Volume 25, Issue 3, 2024

Published on: 31 October, 2023

Page: [200 - 205] Pages: 6

DOI: 10.2174/0113892037276171231016103320

Price: $65

Abstract

Diabetic wound healing is expected to affect 25% of all diabetics, resulting in less severe external factors, economic costs, and less trauma. Topical formulations have been continually improved to achieve a range of amazing properties and have had a significant impact on the management of diabetic wounds. Topical insulin has become one of the most attractive and convenient wound healing techniques due to its excellent biocompatibility, water retention, and therapeutic properties. Multiple versatile topical insulins have been identified and have shown promise over the past few years as they greatly facilitate the management of diabetic wounds as we understand their etiology. The physiological wound healing process repairs damaged tissue and restores skin integrity. For about a century, insulin, a powerful healing agent, and it has been utilized in several clinical and experimental researches research studies to accelerate the healing of various injuries.

« Previous Next »
Graphical Abstract

[1]
Tan, S.Y.; Mei Wong, J.L.; Sim, Y.J.; Wong, S.S.; Mohamed Elhassan, S.A.; Tan, S.H.; Ling Lim, G.P.; Rong Tay, N.W.; Annan, N.C.; Bhattamisra, S.K.; Candasamy, M. Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention. Diabetes Metab. Syndr., 2019, 13(1), 364-372.
[http://dx.doi.org/10.1016/j.dsx.2018.10.008] [PMID: 30641727]
[2]
Chaudhary, N.; Tyagi, N. Diabetes mellitus: An Overview. Int. J. Res. Dev. Pharm. Life Sci., 2018, 7(4), 3030-3033.
[http://dx.doi.org/10.21276/IJRDPL.2278-0238.2018.7(4).3030-3033]
[3]
Galicia-Garcia, U.; Benito-Vicente, A.; Jebari, S.; Larrea-Sebal, A.; Siddiqi, H.; Uribe, K.B.; Ostolaza, H.; Martín, C. Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci., 2020, 21(17), 6275.
[http://dx.doi.org/10.3390/ijms21176275] [PMID: 32872570]
[4]
Dinh, T.; Elder, S.; Veves, A. Delayed wound healing in diabetes: Considering future treatments. Diabetes Manag., 2011, 1(5), 509-519.
[http://dx.doi.org/10.2217/dmt.11.44]
[5]
Greenhalgh, D.G. Wound healing and diabetes mellitus. Clin. Plast. Surg., 2003, 30(1), 37-45.
[http://dx.doi.org/10.1016/S0094-1298(02)00066-4] [PMID: 12636214]
[6]
Sargen, M.R.; Hoffstad, O.; Margolis, D.J. Geographic variation in Medicare spending and mortality for diabetic patients with foot ulcers and amputations. J. Diabetes Complications, 2013, 27(2), 128-133.
[http://dx.doi.org/10.1016/j.jdiacomp.2012.09.003] [PMID: 23062327]
[7]
Catrina, S.B.; Zheng, X. Disturbed hypoxic responses as a pathogenic mechanism of diabetic foot ulcers. Diabetes Metab. Res. Rev., 2016, 32(S1), 179-185.
[http://dx.doi.org/10.1002/dmrr.2742] [PMID: 26453314]
[8]
Singer, A.J.; Clark, R.A.F. Cutaneous wound healing. N. Engl. J. Med., 1999, 341(10), 738-746.
[http://dx.doi.org/10.1056/NEJM199909023411006] [PMID: 10471461]
[9]
Stojadinovic, O.; Yin, N.; Lehmann, J.; Pastar, I.; Kirsner, R.S.; Tomic-Canic, M. Increased number of Langerhans cells in the epidermis of diabetic foot ulcers correlates with healing outcome. Immunol. Res., 2013, 57(1-3), 222-228.
[http://dx.doi.org/10.1007/s12026-013-8474-z] [PMID: 24277309]
[10]
Maione, A.G.; Smith, A.; Kashpur, O.; Yanez, V.; Knight, E.; Mooney, D.J.; Veves, A.; Tomic-Canic, M.; Garlick, J.A. Altered ECM deposition by diabetic foot ulcer-derived fibroblasts implicates fibronectin in chronic wound repair. Wound Repair Regen., 2016, 24(4), 630-643.
[http://dx.doi.org/10.1111/wrr.12437] [PMID: 27102877]
[11]
Lee, B.; Vouthounis, C.; Stojadinovic, O.; Brem, H.; Im, M.; Tomic-Canic, M. From an enhanceosome to a repressosome: Molecular antagonism between glucocorticoids and EGF leads to inhibition of wound healing. J. Mol. Biol., 2005, 345(5), 1083-1097.
[http://dx.doi.org/10.1016/j.jmb.2004.11.027] [PMID: 15644206]
[12]
Pirilä, E.; Korpi, J.T.; Korkiamäki, T.; Jahkola, T.; Gutierrez-Fernandez, A.; Lopez-Otin, C.; Saarialho-Kere, U.; Salo, T.; Sorsa, T. Collagenase-2 (MMP-8) and matrilysin-2 (MMP-26) expression in human wounds of different etiologies. Wound Repair Regen., 2007, 15(1), 47-57.
[http://dx.doi.org/10.1111/j.1524-475X.2006.00184.x] [PMID: 17244319]
[13]
Muller, M.; Trocme, C.; Lardy, B.; Morel, F.; Halimi, S.; Benhamou, P.Y. Matrix metalloproteinases and diabetic foot ulcers: The ratio of MMP-1 to TIMP-1 is a predictor of wound healing. Diabet. Med., 2008, 25(4), 419-426.
[http://dx.doi.org/10.1111/j.1464-5491.2008.02414.x] [PMID: 18387077]
[14]
Gras, C.; Ratuszny, D.; Hadamitzky, C.; Zhang, H.; Blasczyk, R.; Figueiredo, C. miR-145 contributes to hypertrophic scarring of the skin by inducing myofibroblast activity. Mol. Med., 2015, 21(1), 296-304.
[http://dx.doi.org/10.2119/molmed.2014.00172] [PMID: 25876136]
[15]
Lyttle, B.D.; Vaughn, A.E.; Bardill, J.R.; Apte, A.; Gallagher, L.T.; Zgheib, C.; Liechty, K.W. Effects of microRNAs on angiogenesis in diabetic wounds. Front. Med., 2023, 10, 1140979.
[http://dx.doi.org/10.3389/fmed.2023.1140979] [PMID: 37020673]
[16]
Ozdemir, D.; Feinberg, M.W. MicroRNAs in diabetic wound healing: Pathophysiology and therapeutic opportunities. Trends Cardiovasc. Med., 2019, 29(3), 131-137.
[http://dx.doi.org/10.1016/j.tcm.2018.08.002] [PMID: 30143275]
[17]
Cai, Y.; Zang, G.Y.; Huang, Y.; Sun, Z.; Zhang, L.L.; Qian, Y.J.; Yuan, W.; Wang, Z.Q. Advances in neovascularization after diabetic ischemia. World J. Diabetes, 2022, 13(11), 926-939.
[http://dx.doi.org/10.4239/wjd.v13.i11.926] [PMID: 36437864]
[18]
Costa, P.Z.; Soares, R. Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox. Life Sci., 2013, 92(22), 1037-1045.
[http://dx.doi.org/10.1016/j.lfs.2013.04.001] [PMID: 23603139]
[19]
Hu, H.; Jiang, H.; Ren, H.; Hu, X.; Wang, X.; Han, C. AGEs and chronic subclinical inflammation in diabetes: Disorders of immune system. Diabetes Metab. Res. Rev., 2015, 31(2), 127-137.
[http://dx.doi.org/10.1002/dmrr.2560] [PMID: 24846076]
[20]
Caturano, A.; D’Angelo, M.; Mormone, A.; Russo, V.; Mollica, M.P.; Salvatore, T.; Galiero, R.; Rinaldi, L.; Vetrano, E.; Marfella, R.; Monda, M.; Giordano, A.; Sasso, F.C. Oxidative stress in type 2 diabetes: Impacts from pathogenesis to lifestyle modifications. Curr. Issues Mol. Biol., 2023, 45(8), 6651-6666.
[http://dx.doi.org/10.3390/cimb45080420] [PMID: 37623239]
[21]
Dunnill, C.; Patton, T.; Brennan, J.; Barrett, J.; Dryden, M.; Cooke, J.; Leaper, D.; Georgopoulos, N.T. Reactive oxygen species (ROS) and wound healing: The functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int. Wound J., 2017, 14(1), 89-96.
[http://dx.doi.org/10.1111/iwj.12557] [PMID: 26688157]
[22]
Davis, S.C.; Harding, A.; Gil, J.; Parajon, F.; Valdes, J.; Solis, M.; Higa, A. Effectiveness of a polyhexanide irrigation solution on methicillin-resistant Staphylococcus aureus biofilms in a porcine wound model. Int. Wound J., 2017, 14(6), 937-944.
[http://dx.doi.org/10.1111/iwj.12734] [PMID: 28266133]
[23]
Bain, M.A.; Koullias, G.J.; Morse, K.; Wendling, S.; Sabolinski, M.L. Type I collagen matrix plus polyhexamethylene biguanide antimicrobial for the treatment of cutaneous wounds. J. Comp. Eff. Res., 2020, 9(10), 691-703.
[http://dx.doi.org/10.2217/cer-2020-0058] [PMID: 32476449]
[24]
Lázaro-Martínez, J.L.; Álvaro-Afonso, F.J.; Sevillano-Fernández, D.; García-Álvarez, Y.; Sanz-Corbalan, I.; García-Morales, E. Cellular proliferation, dermal repair, and microbiological effectiveness of ultrasound-assisted wound debridement (UAW) versus standard wound treatment in complicated diabetic foot ulcers (DFU): An open-label randomized controlled trial. J. Clin. Med., 2020, 9(12), 4032.
[http://dx.doi.org/10.3390/jcm9124032] [PMID: 33322200]
[25]
Frykberg, R.G. Topical wound oxygen therapy in the treatment of chronic diabetic foot ulcers. Medicina, 2021, 57(9), 917.
[http://dx.doi.org/10.3390/medicina57090917] [PMID: 34577840]
[26]
Lipsky, B.A.; Berendt, A.R. Hyperbaric oxygen therapy for diabetic foot wounds: Has hope hurdled hype? Diabetes Care, 2010, 33(5), 1143-1145.
[http://dx.doi.org/10.2337/dc10-0393] [PMID: 20427686]
[27]
Mouës, C.M.; van den Bemd, G.J.C.M.; Heule, F.; Hovius, S.E.R. Comparing conventional gauze therapy to vacuum-assisted closure wound therapy: A prospective randomised trial. J. Plast. Reconstr. Aesthet. Surg., 2007, 60(6), 672-681.
[http://dx.doi.org/10.1016/j.bjps.2006.01.041] [PMID: 17485058]
[28]
Vassallo, I.M.; Formosa, C. Comparing calcium alginate dressings to vacuum-assisted closure: A clinical trial. Wounds, 2015, 27(7), 180-190.
[PMID: 26192736]
[29]
Lauer, G.; Sollberg, S.; Cole, M.; Krieg, T.; Eming, S.A.; Flamme, I.; Stürzebecher, J.; Mann, K. Expression and proteolysis of vascular endothelial growth factor is increased in chronic wounds. J. Invest. Dermatol., 2000, 115(1), 12-18.
[http://dx.doi.org/10.1046/j.1523-1747.2000.00036.x] [PMID: 10886501]
[30]
Liu, Y.; Liu, Y.; Deng, J.; Li, W.; Nie, X. Fibroblast growth factor in diabetic foot ulcer: Progress and therapeutic prospects. Front. Endocrinol., 2021, 12, 744868.
[http://dx.doi.org/10.3389/fendo.2021.744868] [PMID: 34721299]
[31]
Lacci, K.M.; Dardik, A. Platelet-rich plasma: Support for its use in wound healing. Yale J. Biol. Med., 2010, 83(1), 1-9.
[PMID: 20351977]
[32]
Deng, J.; Yang, M.; Zhang, X.; Zhang, H. Efficacy and safety of autologous platelet-rich plasma for diabetic foot ulcer healing: A systematic review and meta-analysis of randomized controlled trials. J. Orthop. Surg. Res., 2023, 18(1), 370.
[http://dx.doi.org/10.1186/s13018-023-03854-x] [PMID: 37202812]
[33]
Abdelaal, M.A.; Giovinco, N.A.; Slepian, M.J.; Armstrong, D.G. Tissue repair and wound healing: A trip back to the future. In: Technological Advances in Surgery; Trauma and Critical Care, 2015; pp. 563-571.
[http://dx.doi.org/10.1007/978-1-4939-2671-8_46]
[34]
Spampinato, S.F.; Caruso, G.I.; De Pasquale, R.; Sortino, M.A.; Merlo, S. The treatment of impaired wound healing in diabetes: Looking among old drugs. Pharmaceuticals, 2020, 13(4), 60.
[http://dx.doi.org/10.3390/ph13040060] [PMID: 32244718]
[35]
Wong, A.Y.W.; Ong, B.S.Y.; Lee, A.R.Y.B.; Mai, A.S.; Selvarajan, S.; Lakshminarasappa, S.R.; Tay, S.M. Topical biological agents as adjuncts to improve wound healing in chronic diabetic wounds: A systematic review of clinical evidence and future directions. Cureus, 2022, 14(7), e27180.
[http://dx.doi.org/10.7759/cureus.27180] [PMID: 36035037]
[36]
Cam, M.E.; Ertas, B.; Alenezi, H.; Hazar-Yavuz, A.N.; Cesur, S.; Ozcan, G.S.; Ekentok, C.; Guler, E.; Katsakouli, C.; Demirbas, Z.; Akakin, D.; Eroglu, M.S.; Kabasakal, L.; Gunduz, O.; Edirisinghe, M. Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study. Mater. Sci. Eng. C, 2021, 119, 111586.
[http://dx.doi.org/10.1016/j.msec.2020.111586] [PMID: 33321632]
[37]
Kroeze, K.L.; Vink, L.; Boer, E.M.; Scheper, R.J.; Montfrans, C.; Gibbs, S. Simple wound exudate collection method identifies bioactive cytokines and chemokines in (arterio) venous ulcers. Wound Repair Regen., 2012, 20(3), 294-303.
[http://dx.doi.org/10.1111/j.1524-475X.2012.00789.x] [PMID: 22564225]
[38]
Lima, M. H. M.; Caricilli, A. M.; de Abreu, L. L. 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(5), 1-13.
[39]
Liu, Y.; Dhall, S.; Castro, A.; Chan, A.; Alamat, R.; Martins-Green, M. Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue. Biol. Open, 2018, 7(1), bio026187.
[PMID: 29101099]
[40]
Mady, F.M.; Essa, H.; El-Ammawi, T.; Abdelkader, H.; Hussein, A.K. Formulation and clinical evaluation of silymarin pluronic-lecithin organogels for treatment of atopic dermatitis. Drug Des. Devel. Ther., 2016, 10, 1101-1110.
[PMID: 27022248]
[41]
Belgamwar, VS; Panday, MS; Chauk, DS; Surana, SJ Pluronic lecithin organogel. J. Pharm., 2014, 2(3)

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy