Semin Plast Surg 2021; 35(03): 153-158
DOI: 10.1055/s-0041-1731460
Review Article

Updates in Diabetic Wound Healing, Inflammation, and Scarring

Nina Dasari
1   Division of Plastic Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas
Austin Jiang
1   Division of Plastic Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas
Anna Skochdopole
1   Division of Plastic Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas
Jayer Chung
2   Division of Vascular Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas
Edward M. Reece
1   Division of Plastic Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas
3   Division of Plastic Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas
Joshua Vorstenbosch
4   Division of Plastic Surgery, Department of Surgery, McGill University, Montreal, Canada
Sebastian Winocour
1   Division of Plastic Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas
› Author Affiliations


Diabetic patients can sustain wounds either as a sequelae of their disease process or postoperatively. Wound healing is a complex process that proceeds through phases of inflammation, proliferation, and remodeling. Diabetes results in several pathological changes that impair almost all of these healing processes. Diabetic wounds are often characterized by excessive inflammation and reduced angiogenesis. Due to these changes, diabetic patients are at a higher risk for postoperative wound healing complications. There is significant evidence in the literature that diabetic patients are at a higher risk for increased wound infections, wound dehiscence, and pathological scarring. Factors such as nutritional status and glycemic control also significantly influence diabetic wound outcomes. There are a variety of treatments available for addressing diabetic wounds.

Publication History

Article published online:
15 July 2021

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  • References

  • 1 Division of Diabetes Translation At A Glance | CDC. Published August 24, 2020. Accessed May 2, 2021 at:
  • 2 Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005; 293 (02) 217-228
  • 3 Driver VR, Fabbi M, Lavery LA, Gibbons G. The costs of diabetic foot: the economic case for the limb salvage team. J Vasc Surg 2010; 52 (3, Suppl): 17S-22S
  • 4 Gorecka J, Kostiuk V, Fereydooni A. et al. The potential and limitations of induced pluripotent stem cells to achieve wound healing. Stem Cell Res Ther 2019; 10 (01) 87
  • 5 Okonkwo UA, DiPietro LA. Diabetes and wound angiogenesis. Int J Mol Sci 2017; 18 (07) 1419
  • 6 Wallace HA, Basehore BM, Zito PM. Wound Healing Phases. In: StatPearls. StatPearls Publishing; 2021. Accessed April 25, 2021 at:
  • 7 Zhao R, Liang H, Clarke E, Jackson C, Xue M. Inflammation in chronic wounds. Int J Mol Sci 2016; 17 (12) E2085
  • 8 Davis FM, Kimball A, Boniakowski A, Gallagher K. Dysfunctional wound healing in diabetic foot ulcers: new crossroads. Curr Diab Rep 2018; 18 (01) 2
  • 9 Boniakowski AE, Kimball AS, Jacobs BN, Kunkel SL, Gallagher KA. Macrophage-mediated inflammation in normal and diabetic wound healing. J Immunol 2017; 199 (01) 17-24
  • 10 Rosique RG, Rosique MJ, Farina Junior JA. Curbing Inflammation in skin wound healing: a review. Int J Inflamm 2015; 2015: 316235
  • 11 den Dekker A, Davis FM, Kunkel SL, Gallagher KA. Targeting epigenetic mechanisms in diabetic wound healing. Transl Res 2019; 204: 39-50
  • 12 Mahdavian Delavary B, van der Veer WM, van Egmond M, Niessen FB, Beelen RHJ. Macrophages in skin injury and repair. Immunobiology 2011; 216 (07) 753-762
  • 13 Boyce DE, Ciampolini J, Ruge F, Murison MS, Harding KG. Inflammatory-cell subpopulations in keloid scars. Br J Plast Surg 2001; 54 (06) 511-516
  • 14 Mirza RE, Fang MM, Weinheimer-Haus EM, Ennis WJ, Koh TJ. Sustained inflammasome activity in macrophages impairs wound healing in type 2 diabetic humans and mice. Diabetes 2014; 63 (03) 1103-1114
  • 15 Demidova-Rice TN, Durham JT, Herman IM. Wound healing angiogenesis: innovations and challenges in acute and chronic wound healing. Adv Wound Care (New Rochelle) 2012; 1 (01) 17-22
  • 16 Patel S, Srivastava S, Singh MR, Singh D. Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomed Pharmacother 2019; 112: 108615
  • 17 Greenhalgh DG. Wound healing and diabetes mellitus. Clin Plast Surg 2003; 30 (01) 37-45
  • 18 Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res 2017; 58 (1-2): 81-94
  • 19 Minossi JG, Lima Fde O, Caramori CA. et al. Alloxan diabetes alters the tensile strength, morphological and morphometric parameters of abdominal wall healing in rats. Acta Cir Bras 2014; 29 (02) 118-124
  • 20 Berlanga-Acosta J, Schultz GS, López-Mola E, Guillen-Nieto G, García-Siverio M, Herrera-Martínez L. Glucose toxic effects on granulation tissue productive cells: the diabetics' impaired healing. BioMed Res Int 2013; 2013: 256043
  • 21 Martin ET, Kaye KS, Knott C. et al. Diabetes and risk of surgical site infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 2016; 37 (01) 88-99
  • 22 Kantar RS, Rifkin WJ, Wilson SC. et al. Abdominal panniculectomy: determining the impact of diabetes on complications and risk factors for adverse events. Plast Reconstr Surg 2018; 142 (04) 462e-471e
  • 23 Kao AM, Arnold MR, Augenstein VA, Heniford BT. Prevention and treatment strategies for mesh infection in abdominal wall reconstruction. Plast Reconstr Surg 2018; 142 (3, Suppl): 149S-155S
  • 24 Chatterjee A, Nahabedian MY, Gabriel A. et al. Early assessment of post-surgical outcomes with pre-pectoral breast reconstruction: a literature review and meta-analysis. J Surg Oncol 2018; 117 (06) 1119-1130
  • 25 Dortch JD, Eck DL, Ladlie B, TerKonda SP. Perioperative glycemic control in plastic surgery: review and discussion of an institutional protocol. Aesthet Surg J 2016; 36 (07) 821-830
  • 26 Hanemann Jr MS, Grotting JC. Evaluation of preoperative risk factors and complication rates in cosmetic breast surgery. Ann Plast Surg 2010; 64 (05) 537-540
  • 27 Bamba R, Gupta V, Shack RB, Grotting JC, Higdon KK. Evaluation of diabetes mellitus as a risk factor for major complications in patients undergoing aesthetic surgery. Aesthet Surg J 2016; 36 (05) 598-608
  • 28 Lipira AB, Sood RF, Tatman PD, Davis JI, Morrison SD, Ko JH. Complications within 30 days of hand surgery: an analysis of 10,646 patients. J Hand Surg Am 2015; 40 (09) 1852-59.e3
  • 29 Brown E, Genoway KA. Impact of diabetes on outcomes in hand surgery. J Hand Surg Am 2011; 36 (12) 2067-2072
  • 30 Federer AE, Baumgartner RE, Cunningham DJ, Mithani SK. Increased rate of complications following trigger finger release in diabetic patients. Plast Reconstr Surg 2020; 146 (04) 420e-427e
  • 31 Werner BC, Teran VA, Deal DN. Patient-related risk factors for infection following open carpal tunnel release: an analysis of over 450,000 Medicare patients. J Hand Surg Am 2018; 43 (03) 214-219
  • 32 Raikundalia M, Svider PF, Hanba C. et al. Facial fracture repair and diabetes mellitus: an examination of postoperative complications. Laryngoscope 2017; 127 (04) 809-814
  • 33 Molnar JA, Vlad LG, Gumus T. Nutrition and chronic wounds: improving clinical outcomes. Plast Reconstr Surg 2016; 138 (3, Suppl): 71S-81S
  • 34 Zhang S-S, Tang Z-Y, Fang P, Qian H-J, Xu L, Ning G. Nutritional status deteriorates as the severity of diabetic foot ulcers increases and independently associates with prognosis. Exp Ther Med 2013; 5 (01) 215-222
  • 35 Tatti P, Barber A. The Use of a Specialized nutritional supplement for diabetic foot ulcers reduces the use of antibiotics. J Clin Endocrinol Metab 2012; 2 (01) 26-31
  • 36 Abdel-Salam BKA-H. Modulatory effect of whey proteins in some cytokines involved in wound healing in male diabetic albino rats. Inflammation 2014; 37 (05) 1616-1622
  • 37 Niu Y, Cao X, Song F. et al. Reduced dermis thickness and AGE accumulation in diabetic abdominal skin. Int J Low Extrem Wounds 2012; 11 (03) 224-230
  • 38 Van Putte L, De Schrijver S, Moortgat P. The effects of advanced glycation end products (AGEs) on dermal wound healing and scar formation: a systematic review. Scars Burn Heal 2016; 2: 2059513116676828
  • 39 Uribarri J, Woodruff S, Goodman S. et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 2010; 110 (06) 911-16.e12
  • 40 Akhtar S, Barash PG, Inzucchi SE. Scientific principles and clinical implications of perioperative glucose regulation and control. Anesth Analg 2010; 110 (02) 478-497
  • 41 Understanding A1C. American Diabetes Association. Accessed April 28, 2021 at:
  • 42 Cunningham DJ, Baumgartner RE, Federer AE, Richard MJ, Mithani SK. Elevated preoperative hemoglobin A1c associated with increased wound complications in diabetic patients undergoing primary, open carpal tunnel release. Plast Reconstr Surg 2019; 144 (04) 632e-638e
  • 43 Dronge AS, Perkal MF, Kancir S, Concato J, Aslan M, Rosenthal RA. Long-term glycemic control and postoperative infectious complications. Arch Surg 2006; 141 (04) 375-380 , discussion 380
  • 44 Cohen O, Lam G, Choi M, Ceradini D, Karp N. Risk factors for delays in adjuvant chemotherapy following immediate breast reconstruction. Plast Reconstr Surg 2018; 142 (02) 299-305
  • 45 Walker RJ, Strom Williams J, Egede LE. Influence of race, ethnicity and social determinants of health on diabetes outcomes. Am J Med Sci 2016; 351 (04) 366-373
  • 46 Goltsman D, Morrison KA, Ascherman JA. Defining the association between diabetes and plastic surgery outcomes: an analysis of nearly 40,000 patients. Plast Reconstr Surg Glob Open 2017; 5 (08) e1461
  • 47 Abdelhafez AHK, Taha O, Abdelaal M, Al-Najim W, le Roux CW, Docherty NG. Impact of abdominal subcutaneous fat reduction on glycemic control in obese patients with type 2 diabetes mellitus. Bariatr Surg Pract Patient Care 2017; 13 (01) 25-32
  • 48 Climov M, Bayer LR, Moscoso AV, Matsumine H, Orgill DP. The role of dermal matrices in treating inflammatory and diabetic wounds. Plast Reconstr Surg 2016; 138 (3, Suppl): 148S-157S
  • 49 Krug E, Berg L, Lee C. et al; International Expert Panel on Negative Pressure Wound Therapy [NPWT-EP]. Evidence-based recommendations for the use of negative pressure wound therapy in traumatic wounds and reconstructive surgery: steps towards an international consensus. Injury 2011; 42 (Suppl. 01) S1-S12
  • 50 Zhang J, Hu Z-C, Chen D, Guo D, Zhu J-Y, Tang B. Effectiveness and safety of negative-pressure wound therapy for diabetic foot ulcers: a meta-analysis. Plast Reconstr Surg 2014; 134 (01) 141-151
  • 51 Del Pino-Sedeño T, Trujillo-Martín MM, Andia I. et al. Platelet-rich plasma for the treatment of diabetic foot ulcers: a meta-analysis. Wound Repair Regen 2019; 27 (02) 170-182
  • 52 Martí-Carvajal AJ, Gluud C, Nicola S. et al. Growth factors for treating diabetic foot ulcers. Cochrane Database Syst Rev 2015; (10) CD008548
  • 53 Yamakawa S, Hayashida K. Advances in surgical applications of growth factors for wound healing. Burns Trauma 2019; 7 (01) 10
  • 54 Regranex (becaplermin) Information. FDA. Published online November 3, 2018. Accessed May 7, 2021 at:
  • 55 Pourmoussa A, Gardner DJ, Johnson MB, Wong AK. An update and review of cell-based wound dressings and their integration into clinical practice. Ann Transl Med 2016; 4 (23) 457
  • 56 Acellular matrices for the treatment of wounds - Wounds International. Wounds Int.. Published online January 19, 2011. Accessed April 29, 2021 at:
  • 57 Spampinato SF, Caruso GI, De Pasquale R, Sortino MA, Merlo S. The treatment of impaired wound healing in diabetes: looking among old drugs. Pharmaceuticals (Basel) 2020; 13 (04) E60
  • 58 Long M, Cai L, Li W. et al. DPP-4 inhibitors improve diabetic wound healing via direct and indirect promotion of epithelial-mesenchymal transition and reduction of scarring. Diabetes 2018; 67 (03) 518-531
  • 59 Suwanai H, Watanabe R, Sato M, Odawara M, Matsumura H. Dipeptidyl peptidase-4 inhibitor reduces the risk of developing hypertrophic scars and keloids following median sternotomy in diabetic patients: a nationwide retrospective cohort study using the National Database of Health Insurance Claims of Japan. Plast Reconstr Surg 2020; 146 (01) 83-89
  • 60 Maranda EL, Rodriguez-Menocal L, Badiavas EV. Role of mesenchymal stem cells in dermal repair in burns and diabetic wounds. Curr Stem Cell Res Ther 2017; 12 (01) 61-70
  • 61 Liang G, Zhang Y. Genetic and epigenetic variations in iPSCs: potential causes and implications for application. Cell Stem Cell 2013; 13 (02) 149-159
  • 62 Vig S, Dowsett C, Berg L. et al; International Expert Panel on Negative Pressure Wound Therapy [NPWT-EP]. Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: steps towards an international consensus. J Tissue Viability 2011; 20 (Suppl. 01) S1-S18
  • 63 Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther 2014; 31 (08) 817-836
  • 64 Boulton AJM, Armstrong DG, Kirsner RS. et al. Diagnosis and Management of Diabetic Foot Complications. American Diabetes Association; 2018. DOI: 10.2337/db20182-1
  • 65 Patry J, Blanchette V. Enzymatic debridement with collagenase in wounds and ulcers: a systematic review and meta-analysis. Int Wound J 2017; 14 (06) 1055-1065
  • 66 Onesti MG, Fioramonti P, Fino P, Sorvillo V, Carella S, Scuderi N. Effect of enzymatic debridement with two different collagenases versus mechanical debridement on chronic hard-to-heal wounds. Int Wound J 2016; 13 (06) 1111-1115
  • 67 Malone-Povolny MJ, Maloney SE, Schoenfisch MH. Nitric oxide therapy for diabetic wound healing. Adv Healthc Mater 2019; 8 (12) e1801210
  • 68 Erdoğan A, Düzgün AP, Erdoğan K, Özkan MB, Coşkun F. Efficacy of hyperbaric oxygen therapy in diabetic foot ulcers based on Wagner classification. J Foot Ankle Surg 2018; 57 (06) 1115-1119
  • 69 Martínez-Jiménez MA, Aguilar-García J, Valdés-Rodríguez R. et al. Local use of insulin in wounds of diabetic patients: higher temperature, fibrosis, and angiogenesis. Plast Reconstr Surg 2013; 132 (06) 1015e-1019e