Author(s):
Richa Dayaramani, Nipa Gandhi, Areeg Anwar Ali Shamsher, Nour Aymn Ahmad
Email(s):
richadayaramani1976@gmail.com
DOI:
10.52711/0974-360X.2024.00788 
Address:
Richa Dayaramani1, Nipa Gandhi2, Areeg Anwar Ali Shamsher3, Nour Aymn Ahmad4
1Professor, Silver Oak University, Ahmedabad, Gujarat 382481.
2Research Scholar, Gujarat Technological University, Ahmedabad, Gujarat.
3Professor of Pharmacology, RAK Medical and Health Sciences University, UAE.
4Department of Clinical Pharmacy and Pharmacology, RAK Medical and Health Sciences University, UAE.
*Corresponding Author
Published In:
Volume - 17,
Issue - 10,
Year - 2024
ABSTRACT:
Diabetes often leads to foot ulcers, which can impose significant challenges on individuals and the healthcare system, particularly when they reoccur or fail to heal. Diabetic foot ulcers (DFU) are the leading cause of limb loss in diabetic patients, with amputation rates 10-20 times higher than that in non-diabetic individuals. The authors have present a holistic portrayal of diabetic foot ulcer leading to lower limb amputations including the epidemiology, etiopathophysiology in a comprehensive manner. This presents the severity of the Diabetic Foot Ulcer condition prevailing in communities and how it makes the lives difficult for the patients. The article also reviews the pharmacology based treatment options, technology based therapy along with prevention strategies, and nanotechnology based treatment options and advanced technologies that are currently in use and under development to address the issue better. The authors have extensively reviewed the dressings and wound care techniques, novel therapy, management and care strategies to tackle the issue of DFU and proposed the strategies for better management and care regimes so that the Lower limb amputations can be minimized.
Cite this article:
Richa Dayaramani, Nipa Gandhi, Areeg Anwar Ali Shamsher, Nour Aymn Ahmad. Etiopathophysiology, Novel and Advanced Therapy Options, Management and Care Plan to Prevent Lower Limb Amputations for Diabetic Foot Ulcer. Research Journal of Pharmacy and Technology. 2024; 17(10):5141-3. doi: 10.52711/0974-360X.2024.00788
Cite(Electronic):
Richa Dayaramani, Nipa Gandhi, Areeg Anwar Ali Shamsher, Nour Aymn Ahmad. Etiopathophysiology, Novel and Advanced Therapy Options, Management and Care Plan to Prevent Lower Limb Amputations for Diabetic Foot Ulcer. Research Journal of Pharmacy and Technology. 2024; 17(10):5141-3. doi: 10.52711/0974-360X.2024.00788 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2024-17-10-73
REFERENCES:
1. Schaper NC, van Netten JJ, Apelqvist J, Bus SA, Hinchliffe RJ, Lipsky BA; IWGDF Editorial Board. Practical Guidelines on the prevention and management of diabetic foot disease (IWGDF 2019 update). Diabetes Metab Res Rev. 2020 Mar; 36 Suppl 1:e3266. doi: 10.1002/dmrr.3266. PMID: 32176447.
2. Doğruel H, Aydemir M, Balci MK. Management of diabetic foot ulcers and the challenging points: An endocrine view. World J Diabetes. 2022 Jan 15; 13(1): 27-36. doi: 10.4239/wjd.v13.i1.27. PMID: 35070057; PMCID: PMC8771264.
3. IDF Diabetes Atlas report on diabetes foot-related complications – 2022, https://diabetesatlas.org/atlas/diabetic-foot-2022/
4. Eleftheriadou I, Samakidou G, Tentolouris A, Papanas N, Tentolouris N. Nonpharmacological Management of Diabetic Foot Ulcers: An Update. Int J Low Extrem Wounds. 2021 Sep;20(3):188-197. doi: 10.1177/1534734620963561. Epub 2020 Oct 19. PMID: 33073653.
5. Jalilian M, Ahmadi Sarbarzeh P, Oubari S. Factors Related to Severity of Diabetic Foot Ulcer: A Systematic Review. Diabetes Metab Syndr Obes. 2020 May 25; 13: 1835-1842. doi: 10.2147/DMSO.S256243. PMID: 32547145; PMCID: PMC7259447.
6. Yazdanpanah L, Nasiri M, Adarvishi S. Literature review on the management of diabetic foot ulcer. World J Diabetes. 2015 Feb 15;6(1):37-53. doi: 10.4239/wjd.v6.i1.37. PMID: 25685277; PMCID: PMC4317316.
7. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011 Dec; 94(3): 311-21. doi: 10.1016/j.diabres.2011.10.029. Epub 2011 Nov 12. PMID: 22079683.
8. https://vascularsocietyofindia.com/wp-content/uploads/2021/01/LBL-9-Diabetic-foot-Vascular-AW-LQ.pdf
9. Rastogi A, Goyal G, Kesavan R, Bal A, Kumar H, Mangalanadanam, Kamath P, Jude EB, Armstrong DG, Bhansali A. Long term outcomes after incident diabetic foot ulcer: Multicenter large cohort prospective study (EDI-FOCUS investigators) epidemiology of diabetic foot complications study: Epidemiology of diabetic foot complications study. Diabetes Res Clin Pract. 2020 Apr; 162: 108113. doi: 10.1016/j.diabres.2020.108113. Epub 2020 Mar 9. PMID: 32165163.
10. McDermott K, Fang M, Boulton AJM, Selvin E, Hicks CW. Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers. Diabetes Care. 2023 Jan 1;46(1):209-221. doi: 10.2337/dci22-0043. PMID: 36548709; PMCID: PMC9797649.
11. Boyko EJ, Zelnick LR, Braffett BH, Pop-Busui R, Cowie CC, Lorenzi GM, Gubitosi-Klug R, Zinman B, de Boer IH. Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Diabetes Care. 2022 Feb 1; 45(2): 357-364. doi: 10.2337/dc21-1816. PMID: 35007329; PMCID: PMC8914413.
12. Aumiller WD, Dollahite HA. Pathogenesis and management of diabetic foot ulcers. JAAPA. 2015 May;28(5):28-34. doi: 10.1097/01.JAA.0000464276.44117.b1. PMID: 25853673.
13. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017 Jun 15;376(24):2367-2375. doi: 10.1056/NEJMra1615439. PMID: 28614678.
14. Kim J, Nomkhondorj O, An CY, Choi YC, Cho J. Management of diabetic foot ulcers: a narrative review. J Yeungnam Med Sci. 2023 Oct;40(4):335-342. doi: 10.12701/jyms.2023.00682. Epub 2023 Sep 22. PMID: 37735855; PMCID: PMC10626295.
15. Najari HR, Karimian T, Parsa H, QasemiBarqi R, Allami A. Bacteriology of moderate-to-severe diabetic foot infections in two tertiary hospitals of Iran. Foot (Edinb). 2019 Sep;40:54-58. doi: 10.1016/j.foot.2019.05.001. Epub 2019 May 10. PMID: 31102964.
16. Selva Olid A, Solà I, Barajas-Nava LA, Gianneo OD, Bonfill Cosp X, Lipsky BA. Systemic antibiotics for treating diabetic foot infections. Cochrane Database Syst Rev. 2015 Sep 4;2015(9):CD009061. doi: 10.1002/14651858.CD009061.pub2. PMID: 26337865; PMCID: PMC8504988.
17. Ramirez-Acuña JM, Cardenas-Cadena SA, Marquez-Salas PA, Garza-Veloz I, Perez-Favila A, Cid-Baez MA, Flores-Morales V, Martinez-Fierro ML. Diabetic Foot Ulcers: Current Advances in Antimicrobial Therapies and Emerging Treatments. Antibiotics (Basel). 2019 Oct 24;8(4):193. doi: 10.3390/antibiotics8040193. PMID: 31652990; PMCID: PMC6963879.
18. Su J, Li J, Liang J, Zhang K, Li J. Hydrogel Preparation Methods and Biomaterials for Wound Dressing. Life (Basel). 2021 Sep 27;11(10):1016. doi: 10.3390/life11101016. PMID: 34685387; PMCID: PMC8540918.
19. Felgueiras HP. Emerging Antimicrobial and Immunomodulatory Fiber-Based Scaffolding Systems for Treating Diabetic Foot Ulcers. Pharmaceutics. 2023 Jan 11;15(1):258. doi: 10.3390/pharmaceutics15010258. PMID: 36678887; PMCID: PMC9861857.
20. Huang C, Wang R, Yan Z. Silver dressing in the treatment of diabetic foot: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021 Feb 19;100(7):e24876. doi: 10.1097/MD.0000000000024876. PMID: 33607864; PMCID: PMC7899903.
21. Yang B, Wang X, Li Z, Qu Q, Qiu Y. Beneficial effects of silver foam dressing on healing of wounds with ulcers and infection control of burn patients. Pak J Med Sci. 2015 Nov-Dec;31(6):1334-9. doi: 10.12669/pjms.316.7734. PMID: 26870092; PMCID: PMC4744277.
22. Shi C, Wang C, Liu H, Li Q, Li R, Zhang Y, Liu Y, Shao Y, Wang J. Selection of Appropriate Wound Dressing for Various Wounds. Front Bioeng Biotechnol. 2020 Mar 19;8:182. doi: 10.3389/fbioe.2020.00182. PMID: 32266224; PMCID: PMC7096556.
23. Gwak HC, Han SH, Lee J, Park S, Sung KS, Kim HJ, Chun D, Lee K, Ahn JH, Kwak K, Chung HJ. Efficacy of a povidone-iodine foam dressing (Betafoam) on diabetic foot ulcer. Int Wound J. 2020 Feb;17(1):91-99. doi: 10.1111/iwj.13236. Epub 2019 Nov 26. PMID: 31773882; PMCID: PMC7949421.
24. Mathew-Steiner SS, Roy S, Sen CK. Collagen in Wound Healing. Bioengineering. 2021; 8(5):63. https://doi.org/10.3390/bioengineering8050063
25. Wang H. A Review of the Effects of Collagen Treatment in Clinical Studies. Polymers (Basel). 2021 Nov 9;13(22):3868. doi: 10.3390/polym13223868. PMID: 34833168; PMCID: PMC8620403.
26. Martí-Carvajal AJ, Gluud C, Nicola S, Simancas-Racines D, Reveiz L, Oliva P, Cedeño-Taborda J. Growth factors for treating diabetic foot ulcers. Cochrane Database Syst Rev. 2015 Oct 28;2015(10):CD008548. doi: 10.1002/14651858.CD008548.pub2. PMID: 26509249; PMCID: PMC8665376.
27. 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 Feb;34:123-131. doi: 10.1016/j.ctcp.2018.09.004. Epub 2018 Sep 21. PMID: 30712715
28. Li S, Xiao T, Ye N, Yang G, Chen H, Liang X, Li T, Wang J, Peng Y, Li Y, Liu Y. Effect of honey dressing in the management of diabetic foot ulcers: A meta-analysis. Int Wound J. 2023 Sep;20(7):2626-2633. doi: 10.1111/iwj.14135. Epub 2023 Mar 30. PMID: 36994798; PMCID: PMC10410322.
29. Wada FW, Mekonnen MF, Sawiso ED, Kolato S, Woldegiorgis L, Kera GK, El-Khatib Z, Ashuro AA, Biru M, Boltena MT. Bacterial profile and antimicrobial resistance patterns of infected diabetic foot ulcers in sub-Saharan Africa: a systematic review and meta-analysis. Sci Rep. 2023 Sep 5;13(1):14655. doi: 10.1038/s41598-023-41882-z. PMID: 37670001; PMCID: PMC10480146.
30. Moya-Salazar J, Chamana JM, Porras-Rivera D, Goicochea-Palomino EA, Salazar CR, Contreras-Pulache H. Increase in antibiotic resistance in diabetic foot infections among peruvian patients: a single-center cross-sectional study. Front Endocrinol (Lausanne). 2023 Dec 5;14:1267699. doi: 10.3389/fendo.2023.1267699. PMID: 38116313; PMCID: PMC10728874.
31. Liu X, Ren Q, Zhai Y, Kong Y, Chen D, Chang B. Risk Factors for Multidrug-Resistant Organisms Infection in Diabetic Foot Ulcer. Infect Drug Resist. 2022 Apr 7;15:1627-1635. doi: 10.2147/IDR.S359157. PMID: 35418765; PMCID: PMC8999704
32. Caruso P, Maiorino MI, Macera M, Signoriello G, Castellano L, Scappaticcio L, Longo M, Gicchino M, Campitiello F, Bellastella G, Coppola N, Esposito K. Antibiotic resistance in diabetic foot infection: how it changed with COVID-19 pandemic in a tertiary care center. Diabetes Res Clin Pract. 2021 May;175:108797. doi: 10.1016/j.diabres.2021.108797. Epub 2021 Apr 15. PMID: 33845049; PMCID: PMC8047299.
33. Untari EK, Andayani TM, Yasin NM, Asdie RH. A Review of Patient's Knowledge and Practice of Diabetic Foot Self-Care. Malays J Med Sci. 2024 Feb;31(1):33-50. doi: 10.21315/mjms2024.31.1.3. Epub 2024 Feb 20. PMID: 38456109; PMCID: PMC10917598.
34. Huang F, Lu X, Yang Y, Yang Y, Li Y, Kuai L, Li B, Dong H, Shi J. Microenvironment-Based Diabetic Foot Ulcer Nanomedicine. Adv Sci (Weinh). 2023 Jan;10(2):e2203308. doi: 10.1002/advs.202203308. Epub 2022 Nov 24. PMID: 36424137; PMCID: PMC9839871.
35. You J, Liu M, Li M, Zhai S, Quni S, Zhang L, Liu X, Jia K, Zhang Y, Zhou Y. The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering. Int J Mol Sci. 2023 Apr 28;24(9):8029. doi: 10.3390/ijms24098029. PMID: 37175732; PMCID: PMC10179302.
36. Zhu Y, Chang B, Pang Y, Wang H, Zhou Y. Advances in Hypoxia-Inducible Factor-1α Stabilizer Deferoxamine in Tissue Engineering. Tissue Eng Part B Rev. 2023 Aug;29(4):347-357. doi: 10.1089/ten.TEB.2022.0168. Epub 2023 Feb 1. PMID: 36475887.
37. Awasthi A, Singh SK, Kumar B, Gulati M, Kumar R, Wadhwa S, Khursheed R, Corrie L, Kr A, Kumar R, Patni P, Kaur J, Vishwas S, Yadav A. Treatment Strategies Against Diabetic Foot Ulcer: Success so Far and the Road Ahead. Curr Diabetes Rev. 2021;17(4):421-436. doi: 10.2174/1573399816999201102125537. PMID: 33143613.
38. Hotkar MS, Avachat AM, Bhosale SS, Oswal YM. Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes-induced foot ulcer. Int Wound J. 2015 Apr;12(2):210-7. doi: 10.1111/iwj.12084. Epub 2013 Jun 3. PMID: 23731451; PMCID: PMC7950354.
39. Lopez-de la Mora DA, Sanchez-Roque C, Montoya-Buelna M, Sanchez-Enriquez S, Lucano-Landeros S, Macias-Barragan J, Armendariz-Borunda J. Role and New Insights of Pirfenidone in Fibrotic Diseases. Int J Med Sci. 2015 Oct 14;12(11):840-7. doi: 10.7150/ijms.11579. PMID: 26640402; PMCID: PMC4643073.
40. Bardill JR, Laughter MR, Stager M, Liechty KW, Krebs MD, Zgheib C. Topical gel-based biomaterials for the treatment of diabetic foot ulcers. Acta Biomater. 2022 Jan 15;138:73-91. doi: 10.1016/j.actbio.2021.10.045. Epub 2021 Oct 30. PMID: 34728428; PMCID: PMC8738150.
41. Rosenkranz HS, Rosenkranz S. Silver sulfadiazine: interaction with isolated deoxyribonucleic acid. Antimicrob Agents Chemother. 1972 Nov;2(5):373-83. doi: 10.1128/AAC.2.5.373. PMID: 4677596; PMCID: PMC444323.
42. Tian J, Wong KK, Ho CM, Lok CN, Yu WY, Che CM, Chiu JF, Tam PK. Topical delivery of silver nanoparticles promotes wound healing. ChemMedChem. 2007 Jan;2(1):129-36. doi: 10.1002/cmdc.200600171. PMID: 17075952.
43. Tavares G, Alves P, Simões P. Recent Advances in Hydrogel-Mediated Nitric Oxide Delivery Systems Targeted for Wound Healing Applications. Pharmaceutics. 2022 Jun 29;14(7):1377. doi: 10.3390/pharmaceutics14071377. PMID: 35890273; PMCID: PMC9315818.
44. Seabra AB, de Lima R, Calderón M. Nitric oxide releasing nanomaterials for cancer treatment: current status and perspectives. Curr Top Med Chem. 2015;15(4):298-308. doi: 10.2174/1568026615666150108122918. PMID: 25579351.
45. Nazarizadeh A, Asri-Rezaie S. Comparative Study of Antidiabetic Activity and Oxidative Stress Induced by Zinc Oxide Nanoparticles and Zinc Sulfate in Diabetic Rats. AAPS PharmSciTech. 2016 Aug;17(4):834-43. doi: 10.1208/s12249-015-0405-y. Epub 2015 Sep 8. PMID: 26349687.
46. Shen C, James SA, de Jonge MD, Turney TW, Wright PF, Feltis BN. Relating cytotoxicity, zinc ions, and reactive oxygen in ZnO nanoparticle-exposed human immune cells. Toxicol Sci. 2013 Nov;136(1):120-30. doi: 10.1093/toxsci/kft187. Epub 2013 Aug 31. PMID: 23997113.
47. Fu K, Zheng X, Chen Y, Wu L, Yang Z, Chen X, Song W. Role of matrix metalloproteinases in diabetic foot ulcers: Potential therapeutic targets. Front Pharmacol. 2022 Oct 20;13:1050630. doi: 10.3389/fphar.2022.1050630. PMID: 36339630; PMCID: PMC9631429.
48. Sridharan K, Sivaramakrishnan G. Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials. Br J Clin Pharmacol. 2018 Mar;84(3):434-444. doi: 10.1111/bcp.13470. Epub 2018 Jan 5. PMID: 29148070; PMCID: PMC5809344.
49. Gonchar IV, Lipunov AR, Afanasov IM, Larina V, Faller AP, Kibardin AV. Platelet rich plasma and growth factors cocktails for diabetic foot ulcers treatment: State of art developments and future prospects. Diabetes Metab Syndr. 2018 Apr-Jun;12(2):189-194. doi: 10.1016/j.dsx.2017.09.007. Epub 2017 Sep 21. PMID: 29050916.
50. Bui TQ, Bui QVP, Németh D, Hegyi P, Szakács Z, Rumbus Z, Tóth B, Emri G, Párniczky A, Sarlós P, Varga O. Epidermal Growth Factor is Effective in the Treatment of Diabetic Foot Ulcers: Meta-Analysis and Systematic Review. Int J Environ Res Public Health. 2019 Jul 19;16(14):2584. doi: 10.3390/ijerph16142584. PMID: 31331038; PMCID: PMC6678975.
51. Zhao DY, Su YN, Li YH, Yu TQ, Li J, Tu CQ. Efficacy and safety of recombinant human epidermal growth factor for diabetic foot ulcers: A systematic review and meta-analysis of randomised controlled trials. Int Wound J. 2020 Aug;17(4):1062-1073. doi: 10.1111/iwj.13377. Epub 2020 Apr 28. PMID: 32343054; PMCID: PMC7948637.
52. Thanigaimani S, Jin H, Ahmad U, Anbalagan R, Golledge J. Comparative efficacy of growth factor therapy in healing diabetes-related foot ulcers: A network meta-analysis of randomized controlled trials. Diabetes Metab Res Rev. 2023 Jul;39(5):e3670. doi: 10.1002/dmrr.3670. Epub 2023 Jun 5. PMID: 37277960; PMCID: PMC10909411.
53. Zubair M, Ahmad J. Role of growth factors and cytokines in diabetic foot ulcer healing: A detailed review. Rev Endocr Metab Disord. 2019 Jun;20(2):207-217. doi: 10.1007/s11154-019-09492-1. PMID: 30937614.
54. Lopes L, Setia O, Aurshina A, Liu S, Hu H, Isaji T, Liu H, Wang T, Ono S, Guo X, Yatsula B, Guo J, Gu Y, Navarro T, Dardik A. Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research. Stem Cell Res Ther. 2018 Jul 11;9(1):188. doi: 10.1186/s13287-018-0938-6. PMID: 29996912; PMCID: PMC6042254.
55. Da Silva J, Leal EC, Carvalho E. Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers. Biomolecules. 2021 Dec 17;11(12):1894. doi: 10.3390/biom11121894. PMID: 34944538; PMCID: PMC8699205.
56. Haidari H, Melguizo-Rodríguez L, Cowin AJ, Kopecki Z. Therapeutic potential of antimicrobial peptides for treatment of wound infection. Am J Physiol Cell Physiol. 2023 Jan 1;324(1):C29-C38. doi: 10.1152/ajpcell.00080.2022. Epub 2022 Nov 21. PMID: 36409176.
57. Gomes A, Teixeira C, Ferraz R, Prudêncio C, Gomes P. Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other Infected Skin Injuries. Molecules. 2017 Oct 18;22(10):1743. doi: 10.3390/molecules22101743. PMID: 29057807; PMCID: PMC6151519.
58. El Hage R, Knippschild U, Arnold T, Hinterseher I. Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer. Biomedicines. 2022 Jun 25;10(7):1507. doi: 10.3390/biomedicines10071507. PMID: 35884812; PMCID: PMC9312797.
59. Heublein H, Bader A, Giri S. Preclinical and clinical evidence for stem cell therapies as treatment for diabetic wounds. Drug Discov Today. 2015 Jun;20(6):703-17. doi: 10.1016/j.drudis.2015.01.005. Epub 2015 Jan 17. PMID: 25603421.
60. Cao Y, Gang X, Sun C, Wang G. Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer. J Diabetes Res. 2017;2017:9328347. doi: 10.1155/2017/9328347. Epub 2017 Mar 12. PMID: 28386568; PMCID: PMC5366201.
61. Mohammed YA, Farouk HK, Gbreel MI, Ali AM, Salah AA, Nourelden AZ, Gawad MMA. Human amniotic membrane products for patients with diabetic foot ulcers. do they help? a systematic review and meta-analysis. J Foot Ankle Res. 2022 Sep 14;15(1):71. doi: 10.1186/s13047-022-00575-y. PMID: 36104736; PMCID: PMC9472416.
62. Reyzelman AM, Bazarov I. Human acellular dermal wound matrix for treatment of DFU: literature review and analysis. J Wound Care. 2015 Mar;24(3):128; 129-34. doi: 10.12968/jowc.2015.24.3.128. PMID: 25764957.
63. Veves A, Falanga V, Armstrong DG, Sabolinski ML; Apligraf Diabetic Foot Ulcer Study. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care. 2001 Feb;24(2):290-5. doi: 10.2337/diacare.24.2.290. PMID: 11213881.
64. Marston WA, Hanft J, Norwood P, Pollak R; Dermagraft Diabetic Foot Ulcer Study Group. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care. 2003 Jun;26(6):1701-5. doi: 10.2337/diacare.26.6.1701. PMID: 12766097.
65. Pantò F, Adamo L, Giordano C, Licciardello C. Efficacy and safety of photodynamic therapy with RLP068 for diabetic foot ulcers: a review of the literature and clinical experience. Drugs Context. 2020 Feb 10;9:2019-10-3. doi: 10.7573/dic.2019-10-3. Erratum in: Drugs Context. 2020 Apr 21;9: PMID: 32158488; PMCID: PMC7048156.
66. Brandão MGSA, Ximenes MAM, Sousa DF, Veras VS, Barros LM, Rabeh SAN, Costa IG, Araújo TM. Photodynamic therapy for infected foot ulcers in people with diabetes mellitus: a systematic review. Sao Paulo Med J. 2023 May 12;141(6):e2022476. doi: 10.1590/1516-3180.2022.0476.27022023. PMID: 37194764; PMCID: PMC10181837.
67. Ning X, He G, Zeng W, Xia Y. The photosensitizer-based therapies enhance the repairing of skin wounds. Front Med (Lausanne). 2022 Aug 11;9:915548. doi: 10.3389/fmed.2022.915548. PMID: 36035433; PMCID: PMC9403269.
68. Kessler L, Bilbault P, Ortéga F, Grasso C, Passemard R, Stephan D, Pinget M, Schneider F. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care. 2003 Aug;26(8):2378-82. doi: 10.2337/diacare.26.8.2378. PMID: 12882865.
69. Löndahl M. Hyperbaric oxygen therapy as adjunctive treatment for diabetic foot ulcers. Int J Low Extrem Wounds. 2013 Jun;12(2):152-7. doi: 10.1177/1534734613486154. Epub 2013 May 9. PMID: 23667103.
70. Armstrong DG, Lavery LA; Diabetic Foot Study Consortium. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet. 2005 Nov 12;366(9498):1704-10. doi: 10.1016/S0140-6736(05)67695-7. PMID: 16291063.
71. Plikaitis CM, Molnar JA. Subatmospheric pressure wound therapy and the vacuum-assisted closure device: basic science and current clinical successes. Expert Rev Med Devices. 2006 Mar;3(2):175-84. doi: 10.1586/17434440.3.2.175. PMID: 16515384.
72. Najafi B, Mishra R. Harnessing Digital Health Technologies to Remotely Manage Diabetic Foot Syndrome: A Narrative Review. Medicina (Kaunas). 2021 Apr 14;57(4):377. doi: 10.3390/medicina57040377. PMID: 33919683; PMCID: PMC8069817
73. Rasmussen BS, Froekjaer J, Bjerregaard MR, Lauritsen J, Hangaard J, Henriksen CW, Halekoh U, Yderstraede KB. A Randomized Controlled Trial Comparing Telemedical and Standard Outpatient Monitoring of Diabetic Foot Ulcers. Diabetes Care. 2015 Sep;38(9):1723-9. doi: 10.2337/dc15-0332. Epub 2015 Jun 26. PMID: 26116717.
74. Jiang P, Li Q, Luo Y, Luo F, Che Q, Lu Z, Yang S, Yang Y, Chen X, Cai Y. Current status and progress in research on dressing management for diabetic foot ulcer. Front Endocrinol (Lausanne). 2023 Aug 17;14:1221705. doi: 10.3389/fendo.2023.1221705. PMID: 37664860; PMCID: PMC10470649.
75. Gianino E, Miller C, Gilmore J. Smart Wound Dressings for Diabetic Chronic Wounds. Bioengineering (Basel). 2018 Jun 26;5(3):51. doi: 10.3390/bioengineering5030051. PMID: 29949930; PMCID: PMC6163915.
76. Fitzpatrick E, Holland OJ, Vanderlelie JJ. Ozone therapy for the treatment of chronic wounds: A systematic review. Int Wound J. 2018 Aug;15(4):633-644. doi: 10.1111/iwj.12907. Epub 2018 Mar 13. PMID: 29536625; PMCID: PMC7949634.
77. Kushmakov R, Gandhi J, Seyam O, Jiang W, Joshi G, Smith NL, Khan SA. Ozone therapy for diabetic foot. Med Gas Res. 2018 Sep 25;8(3):111-115. doi: 10.4103/2045-9912.241076. PMID: 30319766; PMCID: PMC6178637.
78. Dabó SG; Brandão MGSA; Araújo TM; Frota NM; Veras VS. Tecnologias digitais na prevenção de pé diabético: uma revisão sobre aplicativos móveis. ESTIMA, Braz. J. Enterostomal Ther., 18, 2020: e1420. https://doi.org/10.30886/estima.v18.870_IN
79. Yang L, Rong GC, Wu QN. Diabetic foot ulcer: Challenges and future. World J Diabetes. 2022 Dec 15;13(12):1014-1034. doi: 10.4239/wjd.v13.i12.1014. PMID: 36578870; PMCID: PMC9791573.
80. Chatwin KE, Abbott CA, Boulton AJM, Bowling FL, Reeves ND. The role of foot pressure measurement in the prediction and prevention of diabetic foot ulceration-A comprehensive review. Diabetes Metab Res Rev. 2020 May;36(4):e3258. doi: 10.1002/dmrr.3258. Epub 2019 Dec 11. PMID: 31825163; PMCID: PMC7317473.
81. Xia N, Morteza A, Yang F, Cao H, Wang A. Review of the role of cigarette smoking in diabetic foot. J Diabetes Investig. 2019 Mar;10(2):202-215. doi: 10.1111/jdi.12952. Epub 2018 Nov 12. PMID: 30300476; PMCID: PMC6400172.
82. Sorber R, Abularrage CJ. Diabetic foot ulcers: Epidemiology and the role of multidisciplinary care teams. Semin Vasc Surg. 2021 Mar;34(1):47-53. doi: 10.1053/j.semvascsurg.2021.02.006. Epub 2021 Feb 5. PMID: 33757635.
83. Wang A, Lv G, Cheng X, Ma X, Wang W, Gui J, Hu J, Lu M, Chu G, Chen J, Zhang H, Jiang Y, Chen Y, Yang W, Jiang L, Geng H, Zheng R, Li Y, Feng W, Johnson B, Wang W, Zhu D, Hu Y. Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition). Burns Trauma. 2020 Jul 6;8:tkaa017. doi: 10.1093/burnst/tkaa017. PMID: 32685563; PMCID: PMC7336185.
84. Gallelli G, Cione E, Serra R, Leo A, Citraro R, Matricardi P, Di Meo C, Bisceglia F, Caroleo MC, Basile S, Gallelli L. Nano-hydrogel embedded with quercetin and oleic acid as a new formulation in the treatment of diabetic foot ulcer: A pilot study. Int Wound J. 2020 Apr;17(2):485-490. doi: 10.1111/iwj.13299. Epub 2019 Dec 25. PMID: 31876118; PMCID: PMC7948574.
85. Gourishetti K, Keni R, Nayak PG, Jitta SR, Bhaskaran NA, Kumar L, Kumar N, Krishnadas N, Shenoy RR. Sesamol-Loaded PLGA Nanosuspension for Accelerating Wound Healing in Diabetic Foot Ulcer in Rats. Int J Nanomedicine. 2020 Nov 23;15:9265-9282. doi: 10.2147/IJN.S268941. PMID: 33262587; PMCID: PMC7695744.
86. Sheir MM, Nasra MMA, Abdallah OY. Chitosan alginate nanoparticles as a platform for the treatment of diabetic and non-diabetic pressure ulcers: Formulation and in vitro/in vivo evaluation. Int J Pharm. 2021 Sep 25;607:120963. doi: 10.1016/j.ijpharm.2021.120963. Epub 2021 Aug 4. PMID: 34363919.
87. Bairagi U, Mittal P, Singh J, Mishra B. Preparation, characterization, and in vivo evaluation of nano formulations of ferulic acid in diabetic wound healing. Drug Dev Ind Pharm. 2018 Nov;44(11):1783-1796. doi: 10.1080/03639045.2018.1496448. Epub 2018 Aug 31. PMID: 29973105.
88. Felgueiras HP. Emerging Antimicrobial and Immunomodulatory Fiber-Based Scaffolding Systems for Treating Diabetic Foot Ulcers. Pharmaceutics. 2023 Jan 11;15(1):258. doi: 10.3390/pharmaceutics15010258. PMID: 36678887; PMCID: PMC9861857.
89. Chakraborty, Tulshi and Gupta, Dr. Sumeet and Nair, Anroop and Chauhan, Samrat and Saini, Vipin. (2021). Wound healing potential of insulin-loaded nanoemulsion with Aloe vera gel in diabetic rats. Journal of Drug Delivery Science and Technology. 64. 102601. 10.1016/j.jddst.2021.102601.
90. Yeo E, Yew Chieng CJ, Choudhury H, Pandey M, Gorain B. Tocotrienols-rich naringenin nanoemulgel for the management of diabetic wound: Fabrication, characterization and comparative in vitro evaluations. Curr Res Pharmacol Drug Discov. 2021 Mar 14;2:100019. doi: 10.1016/j.crphar.2021.100019. PMID: 34909654; PMCID: PMC8663980.
91. Nor Azlan AYH, Katas H, Mohamad Zin N, Fauzi MB. Dual action gels containing DsiRNA loaded gold nanoparticles: Augmenting diabetic wound healing by promoting angiogenesis and inhibiting infection. Eur J Pharm Biopharm. 2021 Dec;169:78-90. doi: 10.1016/j.ejpb.2021.09.007. Epub 2021 Sep 25. PMID: 34582971.
92. Eid HM, Ali AA, Ali AMA, Eissa EM, Hassan RM, Abo El-Ela FI, Hassan AH. Potential Use of Tailored Citicoline Chitosan-Coated Liposomes for Effective Wound Healing in Diabetic Rat Model. Int J Nanomedicine. 2022 Feb 5;17:555-575. doi: 10.2147/IJN.S342504. PMID: 35153481; PMCID: PMC8828492.
93. Meamar R, Chegini S, Varshosaz J, Aminorroaya A, Amini M, Siavosh M. Alleviating neuropathy of diabetic foot ulcer by co-delivery of venlafaxine and matrix metalloproteinase drug-loaded cellulose nanofiber sheets: production, in vitro characterization and clinical trial. Pharmacol Rep. 2021 Jun;73(3):806-819. doi: 10.1007/s43440-021-00220-8. Epub 2021 Apr 7. PMID: 33826133.
94. Anand S, Rajinikanth PS, Arya DK, Pandey P, Gupta RK, Sankhwar R, Chidambaram K. Multifunctional Biomimetic Nanofibrous Scaffold Loaded with Asiaticoside for Rapid Diabetic Wound Healing. Pharmaceutics. 2022 Jan 24;14(2):273. doi: 10.3390/pharmaceutics14020273. PMID: 35214006; PMCID: PMC8875374.
95. Ardeshirzadeh A, Ahmadi H, Mirzaei M, Omidi H, Mostafavinia A, Amini A, Bayat S, Fridoni M, Chien S, Bayat M. The combined use of photobiomodulation and curcumin-loaded iron oxide nanoparticles significantly improved wound healing in diabetic rats compared to either treatment alone. Lasers Med Sci. 2022 Dec;37(9):3601-3611. doi: 10.1007/s10103-022-03639-4. Epub 2022 Sep 2. PMID: 36053389.
96. Dubey, K. Sunil,Alexander, Amit,Sivaram, Munnangi,Agrawal, Mukta,Singhvi, Gautam,Sharma, Swapnil, Dayaramani, Richa, Uncovering the Diversification of Tissue Engineering on the Emergent Areas of Stem Cells, Nanotechnology and Biomaterials,Current Stem Cell Research and Therapy, volume 15, issue 3, pages 187-201, year 2020, issn 1574-888X/2212-3946, doi 10.2174/1574888X15666200103124821, (http://www.eurekaselect.com/article/103458, Stem cell tissue engineering nano technology regenerative medicine scaffold transplantation.
97. Saporito F, Sandri G, Bonferoni MC, Rossi S, Boselli C, Icaro Cornaglia A, Mannucci B, Grisoli P, Vigani B, Ferrari F. Essential oil-loaded lipid nanoparticles for wound healing. Int J Nanomedicine. 2017 Dec 27;13:175-186. doi: 10.2147/IJN.S152529. PMID: 29343956; PMCID: PMC5747963.
98. Thattaruparambil Raveendran N, Mohandas A, Ramachandran Menon R, Somasekharan Menon A, Biswas R, Jayakumar R. Ciprofloxacin- and Fluconazole-Containing Fibrin-Nanoparticle-Incorporated Chitosan Bandages for the Treatment of Polymicrobial Wound Infections. ACS Appl Bio Mater. 2019 Jan 22;2(1):243-254. doi: 10.1021/acsabm.8b00585. Epub 2019 Jan 7. PMID: 35016347.
99. Saha K, Ghosh A, Bhattacharya T, Ghosh S, Dey S, Chattopadhyay D. Ameliorative effects of clindamycin - nanoceria conjugate: A ROS responsive smart drug delivery system for diabetic wound healing study. J Trace Elem Med Biol. 2023 Jan;75:127107. doi: 10.1016/j.jtemb.2022.127107. Epub 2022 Nov 12. PMID: 36427436.
100. Zhang P, He L, Zhang J, Mei X, Zhang Y, Tian H, Chen Z. Preparation of novel berberine nano-colloids for improving wound healing of diabetic rats by acting Sirt1/NF-κB pathway. Colloids Surf B Biointerfaces. 2020 Mar;187:110647. doi: 10.1016/j.colsurfb.2019.110647. Epub 2019 Nov 14. PMID: 31761520.
101. Zhu W, Dong Y, Xu P, Pan Q, Jia K, Jin P, Zhou M, Xu Y, Guo R, Cheng B. A composite hydrogel containing resveratrol-laden nanoparticles and platelet-derived extracellular vesicles promotes wound healing in diabetic mice. Acta Biomater. 2022 Dec;154:212-230. doi: 10.1016/j.actbio.2022.10.038. Epub 2022 Oct 27. PMID: 36309190.