Therapeutic angiogenesis modalities represent a broad range of interventions that generate new blood vessel growth to promote neovascularization and tissue repair. Presently, there are three major indications for which angiogenic therapies are in clinical use:
1) chronic wounds (e.g. diabetic lower extremity ulcers, venous leg ulcerations, pressure ulcers, arterial ulcers);
2) peripheral arterial disease; and
3) ischemic heart disease.
In such conditions, the therapeutic goal is to stimulate angiogenesis to improve perfusion, deliver survival factors to sites of tissue repair, mobilize regenerative stem cell populations, and ultimately, restore form and function to the tissue.
Therapeutic Angiogenic Drugs:
- Growth factor-based therapies include the only FDA-approved recombinant protein drug rhPDGF (becaplermin, REGRANEX® 0.01% gel), which is indicated for diabetic neuropathic lower extremity ulcers.
- Growth factors can also be delivered through autologous isolates of patient platelets such as Autologel, SmartPReP.
- Currently, there are no FDA-approved angiogenic drugs for the treatment of ischemic cardiovascular disease.
- Some early stage clinical trials of therapeutic angiogenic agents have demonstrated reductions in symptoms of angina, increase in ability to exercise, and objective evidence of improved perfusion and left ventricular function following therapy.
Therapeutic Angiogenesis Promoting Devices:
- Negative pressure wound therapy (NPWT) such as the Vacuum Assisted Closure (V.A.C.) system induces angiogenesis through tissue microdeformations and mechanochemical coupling and signal transduction.
- MIST ultrasound is a low-frequency and low-intensity non-contact device that results in cell stimulation and increased wound perfusion.
- Hyperbaric Oxygen (HBO) promotes angiogenesis and wound healing by increasing VEGF expression and recruiting endothelial progenitor cells.
- Tissue engineered products approved by the FDA include the bilayered skin substitute Grafstkin (Apligraf®) and the fibroblast dermal skin substitute Dermagraft. These products contain living or cryopreserved cells on a matrix capable of secreting and releasing multiple angiogenic growth factors into the wound bed.
- CD34+ endothelial progenitor cells (EPC) derived from bone marrow or from peripheral blood have been found to enhance angiogenesis in ischemic tissues, increase transcutaneous oxygen, improve ankle-brachial index (ABI), increase collateral vessels by angiography and improve healing of leg ulcers.
- Integra® Dermal Regeneration Template is an advanced skin replacement matrix that consists of a complex three-dimensional porous matrix that acts as a scaffold for cell migration and allows for regeneration of the dermal layer of the patient’s skin. It can be used for Diabetic Foot Ulcers.
Li VW, Kung EF, Li WW. Molecular Therapy for Wounds: Modalities for stimulating Angiogenesis and Granulation. Manual of Wound Management (Bok Lec, Editor) McGraw Hill, 2004, p. 17-43.
Li W, Talcott K, Zhai A, Kruger E, Li V. The Role of Therapeutic Angiogenesis in Tissue Repair and Regeneration Adv Skin Wound Care 2005;18:491-500
Smiell JM, Wieman TJ, Steed DL, et al. Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies. Wound Repair Regen. 1999;7:335-346.