Growth factors for treating chronic venous leg ulcers: A systematic review and meta-analysis

Wound Repair Regen. 2022 Jan;30(1):117-125. doi: 10.1111/wrr.12982. Epub 2021 Nov 16.


Chronic venous leg ulcers (VLU) are wounds that commonly occur due to venous insufficiency. Many growth factors have been introduced over the past two decades to treat VLU. This systematic review and meta-analysis evaluates the impact of growth factor treatments of VLU in comparison to control for complete wound healing, percent reduction in wound area, time to wound healing, and adverse events. A systematic review and meta-analysis of randomised trials was conducted. MEDLINE and EMBASE were searched up to December 2020. Studies were included if they compared a growth factor versus placebo or standard care in patients with VLU. From 1645 articles, 13 trials were included (n = 991). There was a significant difference between any growth factor and placebo in complete wound healing (P = 0.04). Any growth factor compared to placebo significantly increased the likelihood of percent wound reduction by 48.80% (P = <0.00001). There was no difference in overall adverse event rate. Most comparisons have low certainty of evidence according to Grading of Recommendations, Assessment, Development, and Evaluation. This meta-analysis suggests that growth factors have a beneficial effect in complete wound healing of VLU. Growth factors may also increase percent reduction in wound area. The suggestion of benefit for growth factors identified in this review is not a strong one based on the low quality of evidence.

Keywords: EGF; GM-CSF; KGF; TGF-β2; growth factors; leg ulcers; platelet-rich plasma; platelets; stasis ulcers; ulcus cruris; varicose ulcers; venous insufficiency; venous ulcers.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Humans
  • Intercellular Signaling Peptides and Proteins / therapeutic use*
  • Varicose Ulcer* / drug therapy
  • Wound Healing*


  • Intercellular Signaling Peptides and Proteins