Research Article
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Clinical outcomes of topical epidermal growth factor in diabetic foot ulcers

Year 2025, Volume: 6 Issue: 1, 39 - 44, 14.02.2025
https://doi.org/10.47582/jompac.1600752

Abstract

Aims: This study aims to evaluate the clinical outcomes of topical epidermal growth factor (EGF) in the treatment of diabetic foot ulcers (DFUs) in outpatient settings. It also seeks to provide guidance on the use of topical EGF, which is eligible for reimbursement for treating DFUs in our country.
Methods: A retrospective analysis involved 55 patients with DFUs who received topical EGF treatment. Patients received training on EGF application and were monitored for healing outcomes. Data were collected from medical records, including demographic information, wound characteristics, and laboratory results. Statistical analysis was performed using IBM SPSS version 25, employing chi-square, Pearson's correlation, and ANOVA tests to evaluate healing rates and associated factors.
Results: The study found that 70.9% of patients achieved complete wound closure within an average of 15.44 weeks. Healing rates were significantly higher for non-plantar wounds (83.8%) compared to plantar wounds (44.4%). Factors such as age, body weight, and body-mass index (BMI) were identified as influencing healing outcomes, with higher weights and BMI correlating with lower healing rates. Mild skin irritation was the only adverse effect reported.
Conclusion: Topical EGF demonstrates promising potential for enhancing the healing of DFUs in outpatient settings, achieving a healing rate comparable to specialized diabetic foot centers. The findings underscore the importance of considering patient specific factors, such as obesity and adherence to treatment recommendations, to optimize healing outcomes. Further research with larger, multi-center studies is necessary to validate these results and improve access to effective treatments for patients with DFUs.

Ethical Statement

Approval was granted by the Ethics Committee of Kayseri City Hospital, number 237, on November 05, 2024.

Thanks

We thank Mustafa Özturk for his valuable contribution.

References

  • McDermott K, Fang M, Boulton AJM, Selvin E, Hicks CW. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers. Diabetes Care. 2023;46(1):209-221. doi:10.2337/dci22-0043
  • Baig MS, Banu A, Zehravi M, et al. An overview of diabetic foot ulcers and associated problems with special emphasis on treatments with antimicrobials. Life (Basel). 2022;12(7):1054. doi:10.3390/life12071054
  • Vaidyanathan, L. Growth factors in wound healing—a review. Biomed Pharmacol J. 2021;14:1469-1480. doi:10.13005/bpj/2249
  • Zheng SY, Wan XX, Kambey PA, et al. Therapeutic role of growth factors in treating diabetic wound. World J Diabetes. 2023;14(4):364-395. doi:10.4239/wjd.v14.i4.364
  • Yang Y, Luo R, Chao S, et al. Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation. Nat Commun. 2022;13(1):6908. doi:10.1038/s 41467-022-34716-5
  • Han CM, Cheng B, Wu P; writing group of growth factor guideline on behalf of Chinese Burn Association. Clinical guideline on topical growth factors for skin wounds. Burns Trauma. 2020;8:tkaa035. doi:10.1093/burnst/tkaa035
  • Yang Q, Zhang Y, Yin H, Lu Y. Topical recombinant human epidermal growth factor for diabetic foot ulcers: a meta-analysis of randomized controlled clinical trials. Ann Vasc Surg. 2020;62:442-451. doi:10.1016/j.avsg.2019.05.041
  • Kurtuluş B, Aydın E. The use of intralesional epidermal growth factor in the treatment of diabetic foot ulcers. J Med Palliat Care. 2023;4(6):607-612. doi:10.47582/jompac.1350351
  • Aktaş Ş, Baktıroğlu S, Demir L, et al. Intralesional application of epidermal growth factor in limb-threatening ischemic diabetic foot ulcers. Acta Orthop Traumatol Turc. 2016;50(3):277-283. doi:10.3944/AOTT.2015.14.0434
  • Swaminathan N, Awuah WA, Bharadwaj HR, et al. Early intervention and care for diabetic foot ulcers in low and middle income countries: addressing challenges and exploring future strategies: a narrative review. Health Sci Rep. 2024;7(5):e2075. doi:10.1002/hsr2.2075
  • Van GH, Amouyal C, Bourron O, et al. Diabetic foot ulcer management in a multidisciplinary foot centre: one-year healing, amputation and mortality rate. J Wound Care. 2021;30(Sup6):S34-S41. doi:10.12968/jowc.2021.30.Sup6.S34
  • Akturk A, van Netten JJ, Scheer R, Vermeer M, van Baal JG. Ulcer-free survival days and ulcer healing in patients with diabetic foot ulcers: a prospective cohort study. Int Wound J. 2019;16(6):1365-1372. doi:10. 1111/iwj.13199
  • McPherson M, Carroll M, Stewart S. Patient-perceived and practitioner-perceived barriers to accessing foot care services for people with diabetes mellitus: a systematic literature review. J Foot Ankle Res. 2022;15(1):92. doi:10.1186/s13047-022-00597-6
  • 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;17(4):1062-1073. doi:10.1111/iwj.13377
  • Wong AYW, Hooi NMF, Yeo BSY, et al. Improving diabetic wound-healing outcomes with topical growth factor therapies. J Clin Endocrinol Metab. 2024;109(8):e1642-e1651. doi:10.1210/clinem/dgae128
  • Rahim F, Yan X, Shah JA, et al. Epidermal growth factor outperforms placebo in the treatment of diabetic foot ulcer: a meta-analysis. F1000Res. 2023;11(9):773. doi:10.12688/f1000research.121712.2
  • Accattato F, Greco M, Pullano SA, et al. Effects of acute physical exercise on oxidative stress and inflammatory status in young, sedentary obese subjects. PLoS One. 2017;12(6):e0178900. doi:10.1371/journal.pone. 0178900
  • Miller JA, Thompson PA, Hakim IA, et al. Expression of epidermal growth factor, transforming growth factor-β1 and adiponectin in nipple aspirate fluid and plasma of pre and post-menopausal women. Biomark Res. 2013;1(1):18. doi:10.1186/2050-7771-1-18
  • Cotterell A, Griffin M, Downer MA, Parker JB, Wan D, Longaker MT. Understanding wound healing in obesity. World J Exp Med. 2024;14(1): 86898. doi:10.5493/wjem.v14.i1.86898
  • Frasca D, Strbo N. Effects of obesity on infections with emphasis on skin infections and wound healing. J Dermatol Skin Sci. 2022;4(3):5-10. doi: 10.29245/2767-5092/2022/3.1157
  • Berlanga-Acosta J, Garcia-Ojalvo A, Fernández-Montequin J, et al. Epidermal growth factor ıntralesional delivery in chronic wounds: the pioneer and standalone technique for reversing Wound chronicity and promoting sustainable healing. Int J Mol Sci. 2024;25(20):10883. doi:10. 3390/ijms252010883
  • van de Vyver M. Immunology of chronic low-grade inflammation: relationship with metabolic function. J Endocrinol. 2023;257(1):e220271. doi:10.1530/JOE-22-0271
  • Yuan R, Geng S, Chen K, Diao N, Chu HW, Li L. Low-grade inflammatory polarization of monocytes impairs wound healing. J Pathol. 2016;238(4):571-583. doi:10.1002/path.4680
  • Afshari M, Larijani B, Fadayee M, et al. Farzaneh efficacy of topical epidermal growth factor in healing diabetic foot ulcers. Therapy. 2005; 2(5):759-765. doi:10.2217/14750708.2.5.759
  • Park KH, Han SH, Hong JP, et al. Topical epidermal growth factor spray for the treatment of chronic diabetic foot ulcers: a phase III multicenter, double-blind, randomized, placebo-controlled trial. Diabetes Res Clin Pract. 2018;100(142):335-344. doi:10.1016/j.diabres.2018.06.002
  • Khalid KA, Nawi AFM, Zulkifli N, Barkat MA, Hadi H. Aging and wound healing of the skin: a review of clinical and pathophysiological hallmarks. Life (Basel). 2022;12(12):2142. doi:10.3390/life12122142
  • Richard JL, Parer-Richard C, Daures JP, et al. Effect of topical basic fibroblast growth factor on the healing of chronic diabetic neuropathic ulcer of the foot. A pilot, randomized, double-blind, placebo-controlled study. Diabetes Care. 1995;18(1):64-69. doi:10.2337/diacare.18.1.64
  • Bhansali A, Venkatesh S, Dutta P, Dhillon MS, Das S, Agrawal A. Which is the better option: recombinant human PDGF-BB 0.01% gel or standard wound care, in diabetic neuropathic large plantar ulcers off-loaded by a customized contact cast? Diabetes Res Clin Pract. 2009;83(1):e13-e16. doi:10.1016/j.diabres.2008.10.005
  • Racaru S, Bolton Saghdaoui L, Roy Choudhury J, Wells M, Davies AH. Offloading treatment in people with diabetic foot disease: a systematic scoping review on adherence to foot offloading. Diabetes Metab Syndr. 2022;16(5):102493. doi:10.1016/j.dsx.2022.102493
  • BM Ertugrul, N Yapar, AP Duzgun, et al. Evaluation of the efficacy and safety of topical epidermal growth factor Regen-D® in diabetic foot wounds: a randomised, parallel group phase III study. Diabetic Foot J. 2021;24(2):52-57.
  • Aalaa M, Mehrdad N, Bigdeli S, Dehnad A, Sohrabi Z, Arabshahi KS. Challenges and expectations of diabetic foot care from the patients' point of views. J Diabetes Metab Disord. 2021;20(2):1111-1118. doi:10.1007/s40200-021-00825
  • Hirpha N, Tatiparthi R, Mulugeta T. Diabetic foot self-care practices among adult diabetic patients: a descriptive cross-sectional study. Diabetes Metab Syndr Obes. 2020;13:4779-4786. doi:10.2147/DMSO.S285929
  • Peng M, Zhou Q, Fu X, et al. Health economic indicators in patients with diabetic foot: outpatient multidisciplinary management. Int J Low Extrem Wounds. 2022;21(1):50-56. doi:10.1177/1534734620923439
  • Søndergaard SF, Christensen JF, Dahl M, Drejer M, Høgh A. The interplay between patients and healthcare professionals in a cross-sectoral setting in connection with the treatment and care of patients with diabetic foot ulcers: a realistic evaluation. BMC Health Serv Res. 2024;24(1):782. doi:10.1186/s12913-024-11219-1
  • Tan TW, Crocker RM, Palmer KNB, Gomez C, Armstrong DG, Marrero DG. A qualitative study of barriers to care-seeking for diabetic foot ulceration across multiple levels of the healthcare system. J Foot Ankle Res. 2022;15(1):56. doi:10.1186/s13047-022-00561-4

Diyabetik ayak ülserlerinde topikal epidermal büyüme faktörünün klinik sonuçları

Year 2025, Volume: 6 Issue: 1, 39 - 44, 14.02.2025
https://doi.org/10.47582/jompac.1600752

Abstract

Amaç: Bu çalışma, diyabetik ayak ülserlerinin (DFU) tedavisinde topikal epidermal büyüme faktörünün (EGF) klinik sonuçlarını değerlendirmeyi amaçlamaktadır. Ayrıca, ülkemizde DFU'ların tedavisinde geri ödeme için uygun olan topikal EGF'nin kullanımı konusunda rehberlik sağlamayı amaçlamaktadır.
Yöntemler: Retrospektif analiz, topikal EGF tedavisi alan 55 DFU hastasını kapsamaktadır. Hastalar EGF uygulaması konusunda eğitim aldı ve iyileşme sonuçları açısından izlendi. Veriler demografik bilgiler, yara özellikleri ve laboratuvar sonuçları dahil olmak üzere tıbbi kayıtlardan toplandı. İstatistiksel analiz IBM SPSS versiyon 25 kullanılarak, iyileşme oranlarını ve ilişkili faktörleri değerlendirmek için ki-kare, Pearson korelasyon ve ANOVA testleri kullanılarak gerçekleştirilmiştir.
Sonuçlar: Çalışmada hastaların %70,9'unda ortalama 15,44 hafta içinde tam yara kapanması sağlandı. İyileşme oranları plantar olmayan yaralarda (%83,8) plantar yaralara (%44,4) kıyasla anlamlı derecede yüksekti. Yaş, vücut ağırlığı ve vücut kitle indeksi (VKİ) gibi faktörlerin iyileşme sonuçlarını etkilediği, daha yüksek ağırlık ve VKİ'nin daha düşük iyileşme oranlarıyla korelasyon gösterdiği tespit edilmiştir. Hafif cilt tahrişi bildirilen tek yan etkiydi.
Sonuçlar: Topikal EGF, ayaktan tedavi ortamlarında DFU'ların iyileşmesini arttırmak için umut verici bir potansiyel göstermekte ve özel diyabetik ayak merkezleriyle karşılaştırılabilir bir iyileşme oranı elde etmektedir. Bulgular, iyileşme sonuçlarını optimize etmek için obezite ve tedavi önerilerine bağlılık gibi hastaya özgü faktörlerin dikkate alınmasının önemini vurgulamaktadır. Bu sonuçları doğrulamak ve DFU'lu hastaların etkili tedavilere erişimini iyileştirmek için daha büyük, çok merkezli çalışmalarla daha fazla araştırma yapılması gerekmektedir.

References

  • McDermott K, Fang M, Boulton AJM, Selvin E, Hicks CW. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers. Diabetes Care. 2023;46(1):209-221. doi:10.2337/dci22-0043
  • Baig MS, Banu A, Zehravi M, et al. An overview of diabetic foot ulcers and associated problems with special emphasis on treatments with antimicrobials. Life (Basel). 2022;12(7):1054. doi:10.3390/life12071054
  • Vaidyanathan, L. Growth factors in wound healing—a review. Biomed Pharmacol J. 2021;14:1469-1480. doi:10.13005/bpj/2249
  • Zheng SY, Wan XX, Kambey PA, et al. Therapeutic role of growth factors in treating diabetic wound. World J Diabetes. 2023;14(4):364-395. doi:10.4239/wjd.v14.i4.364
  • Yang Y, Luo R, Chao S, et al. Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation. Nat Commun. 2022;13(1):6908. doi:10.1038/s 41467-022-34716-5
  • Han CM, Cheng B, Wu P; writing group of growth factor guideline on behalf of Chinese Burn Association. Clinical guideline on topical growth factors for skin wounds. Burns Trauma. 2020;8:tkaa035. doi:10.1093/burnst/tkaa035
  • Yang Q, Zhang Y, Yin H, Lu Y. Topical recombinant human epidermal growth factor for diabetic foot ulcers: a meta-analysis of randomized controlled clinical trials. Ann Vasc Surg. 2020;62:442-451. doi:10.1016/j.avsg.2019.05.041
  • Kurtuluş B, Aydın E. The use of intralesional epidermal growth factor in the treatment of diabetic foot ulcers. J Med Palliat Care. 2023;4(6):607-612. doi:10.47582/jompac.1350351
  • Aktaş Ş, Baktıroğlu S, Demir L, et al. Intralesional application of epidermal growth factor in limb-threatening ischemic diabetic foot ulcers. Acta Orthop Traumatol Turc. 2016;50(3):277-283. doi:10.3944/AOTT.2015.14.0434
  • Swaminathan N, Awuah WA, Bharadwaj HR, et al. Early intervention and care for diabetic foot ulcers in low and middle income countries: addressing challenges and exploring future strategies: a narrative review. Health Sci Rep. 2024;7(5):e2075. doi:10.1002/hsr2.2075
  • Van GH, Amouyal C, Bourron O, et al. Diabetic foot ulcer management in a multidisciplinary foot centre: one-year healing, amputation and mortality rate. J Wound Care. 2021;30(Sup6):S34-S41. doi:10.12968/jowc.2021.30.Sup6.S34
  • Akturk A, van Netten JJ, Scheer R, Vermeer M, van Baal JG. Ulcer-free survival days and ulcer healing in patients with diabetic foot ulcers: a prospective cohort study. Int Wound J. 2019;16(6):1365-1372. doi:10. 1111/iwj.13199
  • McPherson M, Carroll M, Stewart S. Patient-perceived and practitioner-perceived barriers to accessing foot care services for people with diabetes mellitus: a systematic literature review. J Foot Ankle Res. 2022;15(1):92. doi:10.1186/s13047-022-00597-6
  • 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;17(4):1062-1073. doi:10.1111/iwj.13377
  • Wong AYW, Hooi NMF, Yeo BSY, et al. Improving diabetic wound-healing outcomes with topical growth factor therapies. J Clin Endocrinol Metab. 2024;109(8):e1642-e1651. doi:10.1210/clinem/dgae128
  • Rahim F, Yan X, Shah JA, et al. Epidermal growth factor outperforms placebo in the treatment of diabetic foot ulcer: a meta-analysis. F1000Res. 2023;11(9):773. doi:10.12688/f1000research.121712.2
  • Accattato F, Greco M, Pullano SA, et al. Effects of acute physical exercise on oxidative stress and inflammatory status in young, sedentary obese subjects. PLoS One. 2017;12(6):e0178900. doi:10.1371/journal.pone. 0178900
  • Miller JA, Thompson PA, Hakim IA, et al. Expression of epidermal growth factor, transforming growth factor-β1 and adiponectin in nipple aspirate fluid and plasma of pre and post-menopausal women. Biomark Res. 2013;1(1):18. doi:10.1186/2050-7771-1-18
  • Cotterell A, Griffin M, Downer MA, Parker JB, Wan D, Longaker MT. Understanding wound healing in obesity. World J Exp Med. 2024;14(1): 86898. doi:10.5493/wjem.v14.i1.86898
  • Frasca D, Strbo N. Effects of obesity on infections with emphasis on skin infections and wound healing. J Dermatol Skin Sci. 2022;4(3):5-10. doi: 10.29245/2767-5092/2022/3.1157
  • Berlanga-Acosta J, Garcia-Ojalvo A, Fernández-Montequin J, et al. Epidermal growth factor ıntralesional delivery in chronic wounds: the pioneer and standalone technique for reversing Wound chronicity and promoting sustainable healing. Int J Mol Sci. 2024;25(20):10883. doi:10. 3390/ijms252010883
  • van de Vyver M. Immunology of chronic low-grade inflammation: relationship with metabolic function. J Endocrinol. 2023;257(1):e220271. doi:10.1530/JOE-22-0271
  • Yuan R, Geng S, Chen K, Diao N, Chu HW, Li L. Low-grade inflammatory polarization of monocytes impairs wound healing. J Pathol. 2016;238(4):571-583. doi:10.1002/path.4680
  • Afshari M, Larijani B, Fadayee M, et al. Farzaneh efficacy of topical epidermal growth factor in healing diabetic foot ulcers. Therapy. 2005; 2(5):759-765. doi:10.2217/14750708.2.5.759
  • Park KH, Han SH, Hong JP, et al. Topical epidermal growth factor spray for the treatment of chronic diabetic foot ulcers: a phase III multicenter, double-blind, randomized, placebo-controlled trial. Diabetes Res Clin Pract. 2018;100(142):335-344. doi:10.1016/j.diabres.2018.06.002
  • Khalid KA, Nawi AFM, Zulkifli N, Barkat MA, Hadi H. Aging and wound healing of the skin: a review of clinical and pathophysiological hallmarks. Life (Basel). 2022;12(12):2142. doi:10.3390/life12122142
  • Richard JL, Parer-Richard C, Daures JP, et al. Effect of topical basic fibroblast growth factor on the healing of chronic diabetic neuropathic ulcer of the foot. A pilot, randomized, double-blind, placebo-controlled study. Diabetes Care. 1995;18(1):64-69. doi:10.2337/diacare.18.1.64
  • Bhansali A, Venkatesh S, Dutta P, Dhillon MS, Das S, Agrawal A. Which is the better option: recombinant human PDGF-BB 0.01% gel or standard wound care, in diabetic neuropathic large plantar ulcers off-loaded by a customized contact cast? Diabetes Res Clin Pract. 2009;83(1):e13-e16. doi:10.1016/j.diabres.2008.10.005
  • Racaru S, Bolton Saghdaoui L, Roy Choudhury J, Wells M, Davies AH. Offloading treatment in people with diabetic foot disease: a systematic scoping review on adherence to foot offloading. Diabetes Metab Syndr. 2022;16(5):102493. doi:10.1016/j.dsx.2022.102493
  • BM Ertugrul, N Yapar, AP Duzgun, et al. Evaluation of the efficacy and safety of topical epidermal growth factor Regen-D® in diabetic foot wounds: a randomised, parallel group phase III study. Diabetic Foot J. 2021;24(2):52-57.
  • Aalaa M, Mehrdad N, Bigdeli S, Dehnad A, Sohrabi Z, Arabshahi KS. Challenges and expectations of diabetic foot care from the patients' point of views. J Diabetes Metab Disord. 2021;20(2):1111-1118. doi:10.1007/s40200-021-00825
  • Hirpha N, Tatiparthi R, Mulugeta T. Diabetic foot self-care practices among adult diabetic patients: a descriptive cross-sectional study. Diabetes Metab Syndr Obes. 2020;13:4779-4786. doi:10.2147/DMSO.S285929
  • Peng M, Zhou Q, Fu X, et al. Health economic indicators in patients with diabetic foot: outpatient multidisciplinary management. Int J Low Extrem Wounds. 2022;21(1):50-56. doi:10.1177/1534734620923439
  • Søndergaard SF, Christensen JF, Dahl M, Drejer M, Høgh A. The interplay between patients and healthcare professionals in a cross-sectoral setting in connection with the treatment and care of patients with diabetic foot ulcers: a realistic evaluation. BMC Health Serv Res. 2024;24(1):782. doi:10.1186/s12913-024-11219-1
  • Tan TW, Crocker RM, Palmer KNB, Gomez C, Armstrong DG, Marrero DG. A qualitative study of barriers to care-seeking for diabetic foot ulceration across multiple levels of the healthcare system. J Foot Ankle Res. 2022;15(1):56. doi:10.1186/s13047-022-00561-4
There are 35 citations in total.

Details

Primary Language English
Subjects Orthopaedics, Underwater and Hyperbaric Medicine
Journal Section Research Articles [en] Araştırma Makaleleri [tr]
Authors

Levent Demir 0000-0001-6600-7414

Murat Kahraman 0000-0002-3821-9767

İbrahim Altun 0000-0002-0152-1065

Mustafa Avcı 0000-0002-5018-9070

Selahattin Kılıç 0000-0002-9146-645X

Sena Aslan 0009-0001-9942-0552

Publication Date February 14, 2025
Submission Date December 13, 2024
Acceptance Date January 27, 2025
Published in Issue Year 2025 Volume: 6 Issue: 1

Cite

AMA Demir L, Kahraman M, Altun İ, Avcı M, Kılıç S, Aslan S. Clinical outcomes of topical epidermal growth factor in diabetic foot ulcers. J Med Palliat Care / JOMPAC / jompac. February 2025;6(1):39-44. doi:10.47582/jompac.1600752

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