Effectiveness of Sucralphate and Platelet-Rich Plasma Combinations For Vascular Endothelial Growth Factor (VEGF) Expression In Diabetic Ulcer Healing


  • Victor Jeremia Syaropi Simanjuntak Master of Biomedical Science Study Program, Faculty of Medicine Diponegoro University, Semarang, Indonesia, Indonesia
  • Renni Yuniati Department of Dermatology & Venereal Diseases, Faculty of Medicine, Diponegoro University, Semarang, Indonesia, Indonesia
  • Yan Wisnu Prajoko Department of Surgery, Faculty of Medicine, Diponegoro University, Semarang, Indonesia, Indonesia
  • Heri Nugroho Hario Seno Department of Internal Medicine Faculty of Medicine Diponegoro University, Semarang, Indonesia, Indonesia
  • Tri Nur Kristina Department of Microbiology Faculty of Medicine Diponegoro University, Semarang, Indonesia, Indonesia




sucralfate, platelete-rich plasma topical, VEGF expression, wound area, side effect, diabetic ulcer


Background: Diabetic ulcer is one of the most feared chronic infections due to Diabetes Mellitus because it can lead to amputation and death.

Aim: To prove the effectiveness of sucralfate and platelet-rich plasma (PRP) combination for Vascular Endothelial Growth Factor (VEGF) expression in diabetic ulcer healing.

Methods: This research is an experimental study of Phase I Clinical Trial with post-test only group design. There were 20 patients with diabetic ulcers divided into two groups, namely the treated group that was given sucralfate and PRP therapy and the control group was given standard therapy of normal saline drainage and gauze covered. Parameters were VEGF expression levels, wound area after being given therapy, and side effect from the treatment. Data on VEGF expression levels were obtained by means of examination with the Quantikine Human VEGF-ELISA Quantikine, R&D System, Inc, Minneapolis. The measurement of the wound area was assessed based on several criteria, namely grade 0 (no change), grade 1 (wound size reduced to less than of the previous wound), grade 2 (wound size was reduced to less than of the previous wound, but granulation was visible), and grade 3 (wound has closed completely).

Result: In unpaired t-test, the mean VEGF expression was 98.18+10.96 in the treatment group and 66.69+23.79 in the control group which showed significant difference in VEGF expression levels (p = 0.003). In Mann-Whitney test, the mean wound area was 0.68+0.40 in the treatment group and 0.77+0.67 in the control group which showed that there was not any significant difference in wound area (p = 0.152). There were no side effects in both study group.

Conclusions: The combination of sucralfate and PRP can increase VEGF levels significantly in diabetic ulcer patients but does not show a different effect in reducing wound area compared to standard treatment. The combination did not cause any side effects in the study subjects, as well as those using standard treatment.


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1. Alavi A, Sibbald RG, Mayer D, Goodman L, Botros M, Armstrong DG, et al. Diabetic foot ulcers: Part I. Pathophysiology and prevention. J Am Acad Dermatol. 2014 Jan;70(1):1.e1-18; quiz 19–20.

2. Wang A, Xu Z, Ji L. [Clinical characteristics and medical costs of diabetics with amputation at central urban hospitals in China]. Zhonghua Yi Xue Za Zhi. 2012 Jan;92(4):224–7.

3. Leone S, Pascale R, Vitale M, Esposito S. [Epidemiology of diabetic foot]. Le Infez Med. 2012;20 Suppl 1:8–13.

4. Abdissa D, Adugna T, Gerema U, Dereje D. Prevalence of Diabetic Foot Ulcer and Associated Factors among Adult Diabetic Patients on Follow-Up Clinic at Jimma Medical Center, Southwest Ethiopia, 2019: An Institutional-Based Cross-Sectional Study. J Diabetes Res [Internet]. 2020 Mar 15;2020:4106383. Available from: https://pubmed.ncbi.nlm.nih.gov/32258165

5. Flahr D. The effect of nonweight-bearing exercise and protocol adherence on diabetic foot ulcer healing: a pilot study. Ostomy Wound Manage. 2010 Oct;56(10):40–50.

6. Setati S, Alwi A, Simadibrata S. Kaki Diabetes: Books of Science of Internal Medicine. Jakarta: Interna Publishing; 2014.

7. Rosyid FN. Etiology, pathophysiology, diagnosis and management of diabetics’ foot ulcer. Int J Res Med Sci. 2017;5(10):4206.

8. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999 Sep;341(10):738–46.

9. Santilli SM, Valusek PA, Robinson C. Use of a noncontact radiant heat bandage for the treatment of chronic venous stasis Adv Wound Care. 1999 Mar;12(2):89–93.

10. Nagalakshmi G, Amalan AJ, Anandan H. Clinical Study of Comparision Between Efficacy of Topical Sucralfate and Conventional Dressing in the Management of Diabetic Ulcer. 2017;5(3):236–8.

11. McGee GS, Davidson JM, Buckley A, Sommer A, Woodward SC, Aquino AM, et al. Recombinant basic fibroblast growth factor accelerates wound healing. J Surg Res. 1988 Jul;45(1):145–53.

12. Anitua E, Alkhraisat MH, Orive G. Perspectives and challenges in regenerative medicine using plasma rich in growth J Control Release. 2012 Jan;157(1):29–38.

13. Grazul-Bilska AT, Johnson ML, Bilski JJ, Redmer DA, Reynolds LP, Abdullah A, et al. Wound healing: the role of growth factors. Drugs Today (Barc). 2003 Oct;39(10):787–800.

14. Carter MJ, Fylling CP, Parnell LKS. Use of platelet rich plasma gel on wound healing: a systematic review and meta-analysis. Eplasty [Internet]. 2011/09/15. 2011;11:e38–e38. Available from: https://pubmed.ncbi.nlm.nih.gov/22028946

15. Villela DL, Lu V. Evidence on the use of platelet-rich plasma for diabetic ulcer : A systematic review. 2010;28(April):111–6.

16. Driver VR, Hanft J, Fylling CP, Beriou JM. A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers. Ostomy Wound Manage. 2006 Jun;52(6):68–70, 72, 74 passim.

17. Singer AJ, Tassiopoulos A, Kirsner RS. Evaluation and Management of Lower-Extremity Ulcers. Vol. 378, The New England journal of medicine. United States; 2018. p. 302–3.

18. Yuniati R, Innelya I, Rachmawati A, et al. Application of Topical Sucralfate and Topical Platelet-Rich Plasma Improves Wound Healing in Diabetic Ulcer Rats Wound Model. Journal of Experimental Pharmacology. 2021:13. 797-806.

19. Sidawy A, Perler B, AbuRahman. Rutherford's Vascular Surgery and Endovascular Therapy: 9th edition: Elsevier: 2019.

20. DeFronzo R. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard lecture 2009. Diabetologia. 2010;53(7):1270–1287.

21. Mills JL, et al. The Society for Vascular Surgery lower extremity threatened limb classification system: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg. 2014;59:220–223.

22. Katz DE, Friedman ND, Ostrovski E, et al. Diabetic foot infection in hospitalized adults. J Infect Chemother. 2016;22:167–173.

23. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017 Jun;376(24):2367–75.

24. Clayton W, Elasy TA. A Review of the Pathophysiology, Classification, and Treatment of Foot Ulcers in Diabetic Patients. Clin Diabetes [Internet]. 2009 Apr 1;27(2):52 LP – 58. Available from: http://clinical.diabetesjournals.org/content/27/2/52.abstract

25. Charles H, Chung K, Gosain A, et al. Grabb and Smith's Plastic Surgery: 7th edition. Wolters Kluwer. 2014.

26. Rosyid F, Dharmana E. Suwondo A, et al. VEGF: Strukture, Biological Activities, Regulations and Role in The Healing of Diabetic ulcers. International Journal of Research in Medical Sciences. 2018 Jul;6(7):2184-2192.

27. Brem H, Tomic-Canic M. Cellular and Molecular Basics of Wound Healing in Diabetes. Journal of Clinical Investigation. 2007 May:117(5):1219-1222.

28. Philip B, Arber K, Tomic-Canic M, et al. The Role of Vascular Endothelial Growth Factor in Wound Healing. Journal of Surgical Researc. 2009:153:347-358

29. David O. Bates O, Pritchard J. The Role of Vascular Endothelial Growth Factor in Wound Healing. International Journal of Lowe Extremity Wounds. 2003:2(107)

30. Wild T, Rahbarnia A, Kellner M, Sobotka L, Eberlein T. Basics in nutrition and wound healing. Nutrition. 2010 Sep;26(9):862–6.

31. Jain A. A new classification of diabetic foot complications: a simple and effective teaching tool. J Diabet Foot Complicat [Internet]. 2012;4(1):1–5. Available from: http://jdfc.org/2012/volume-4-issue-1/a-new-classification-of-diabetic-foot-complications-a-simple-and-effective-teaching-tool/

32. Oyibo SO, Jude EB, Tarawneh I, Nguyen HC, Harkless LB, Boulton AJ. A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems. Diabetes Care. 2001 Jan;24(1):84–8.

33. Masuelli L, Tumino G, Turriziani M, Modesti A, Bei R. Topical Use of Sucralfate in Epithelial Wound Healing: Clinical Evidence and Molecular Mechanisms of Action. Recent Pat Inflamm Allergy Drug Discov. 2009;4(1):25–36.

34. McCarthy DM. Sucralfate. N Engl J Med. 1991 Oct;325(14):1017–25.

35. Yeh BK, Eliseenkova A V, Plotnikov AN, Green D, Pinnell J, Polat T, et al. Structural basis for activation of fibroblast growth factor signaling by sucrose Mol Cell Biol. 2002 Oct;22(20):7184–92.

36. Konturek SJ, Brzozowski T, Majka J, Szlachcic A, Bielanski W, Stachura J, et al. Fibroblast growth factor in gastroprotection and ulcer healing: interaction with Gut. 1993 Jul;34(7):881–7.

37. Hu Y, Guo S, Lu K. [The effect of bFGF and sucralfate on cell proliferation during continuous tissue expansion]. Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese J  Plast Surg. 2003 May;19(3):203–6.

38. Ebner R, Derynck R. Epidermal growth factor and transforming growth factor-alpha: differential intracellular routing and processing of ligand-receptor complexes. Cell Regul. 1991 Aug;2(8):599–612.

39. Sánchez-Fidalgo S, Martín-Lacave I, Illanes M, Motilva V. Angiogenesis, cell proliferation and apoptosis in gastric ulcer healing. Effect of a selective cox-2 inhibitor. Eur J Pharmacol. 2004 Nov;505(1–3):187–94.

40. Burch RM, McMillan BA. Sucralfate induces proliferation of dermal fibroblasts and keratinocytes in culture and granulation tissue formation in full-thickness skin wounds. Agents Actions. 1991 Sep;34(1–2):229–31.

41. Akhundov K, Pietramaggiori G, Waselle L, Darwiche S, Guerid S, Scaletta C, et al. Development of a cost-effective method for platelet-rich plasma (prp) preparation for topical wound healing. Ann Burns Fire Disasters. 2012;25(4):207–13.

42. Suthar M, Gupta S, Bukhari S, Ponemone V. Treatment of chronic non-healing ulcers using autologous platelet rich plasma: a case series. J Biomed Sci. 2017 Feb;24(1):16.

43. Vinay KT, Parijat G. Management of diabetic foot ulcers with platelet rich Plasma : A clinical study. National Journal of Clinical Orthopaedics. 2008;2(3): 09-11

44. Tripathi VK, Gupta P. Management of diabetic foot ulcers with platelet rich plasma: A clinical study. National journal of clinical orthopaedics. 2018 Jun 7;2(3):09-11

45. Harry A, Uma S, Sivaram. Role of platelet rich plasma in treatment of diabetic foot ulcer. Indian journal of Applied Research. 2017 May;7(5):601-602

46. El-rahman MAA, Al-Hayeg OMI, Aboulyazid ABM, Gaafar AM. the role of platelet-rich plasma in the treatment of diabetic foot ulcers. Al-Azhar Med. J. 2020; 49(3):1369-1376

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Syaropi Simanjuntak VJ, Yuniati R, Prajoko YW, Hario Seno HN, Kristina TN. Effectiveness of Sucralphate and Platelet-Rich Plasma Combinations For Vascular Endothelial Growth Factor (VEGF) Expression In Diabetic Ulcer Healing. Medica Hospitalia J. Clin. Med. [Internet]. 2023 Nov. 29 [cited 2024 May 26];10(3):359-63. Available from: http://medicahospitalia.rskariadi.co.id/medicahospitalia/index.php/mh/article/view/862



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