New Research Demonstrates That APLIGRAF® DOWNREGULATES FIBROSIS in Venous Leg Ulcers (VLUs)


Previous clinical research
has shown that Apligraf:

  • Activates keratinocytes at the
    wound edge1,2
  • Regulates and corrects growth
    factor signaling1-5

This new research shows
that Apligraf:

  • Restores fibroblast function at the wound base, thus normalizing ECM production and MMP balance6
  • Downregulates fibrosis formation6
Apligraf—Bioengineered With Living Cells.

Apligraf is indicated for use with standard therapeutic compression for the treatment of non-infected partial and full-thickness skin ulcers due to venous insufficiency of greater than 1 month duration and which have not adequately responded to conventional ulcer therapy.7

Visit for complete prescribing information and contraindications

ECM = Extracellular Matrix; MMP = Matrix Metalloproteinase

References: 1. Stone RC, Stojadinovic O, Rosa AM, et al. A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers. Sci Transl Med. 2017;9(371):eaa8611. doi:10.1126/scitranslmed.aaf8611. 2. Stone RC, Stojadinovic O, Sawaya AP, Rosa AM, Badiavas E, Blumenberg M, Tomic-Canic M. Treatment of chronic venous leg ulcers with bioengineered living cell construct induces metallothioneins and MMP8 to resolve matrix fibrosis and reactivates healthy remodeling response. Abstract presented at SAWC SPRING/WHS (2016). 3. Milstone LM, Asgari MM, Schwartz PM, Hardin-Young J. Growth factor expression, healing, and structural characteristics of Graftskin (Apligraf). Wounds. 2000;12 (5 Suppl A):12A-19A. 4. Falanga V, Isaacs C, Paquette D, et al. Wounding of bioengineered skin: cellular and molecular aspects after injury. J Invest Dermatol. 2002;119(3):653-660. 5. Brem H, Young J, Tomic-Canic M, Isaacs C, Ehrlich HP. Clinical efficacy and mechanism of bilayered living human skin equivalent (HSE) in treatment of diabetic foot ulcers. Surg Technol Int. 2003; 11:23-31. 6. Stone RC, Stojadinovic O, Sawaya AP, Glinos GD, Lindley LE, Pastar I, Badiavas E, Tomic-Canic M. A bioengineered living cell construct activates metallothionein/zinc/MMP8 and inhibits TGFβ to stimulate remodeling of fibrotic venous leg ulcers. Wound Rep Regen. 2019 Oct 31. doi: 10.1111/wrr.12778. [Epub ahead of print] 7. Apligraf [packaging insert]. Canton, MA: Organogenesis; 2017.