Interventions and platforms that direct lymphangiogenesis to restore physiological homeostasis and enhance immunoregulation

The lymphatic system maintains physiological homeostasis through constant immunosurveillance, immune cell trafficking, and regulation of interstitial fluid flow. Lymphatic dysfunction is associated with a wide range of pathologies, including cancer metastasis and lymphedema. Aberrant lymphatic structure also contributes to chronic wounds and transplanted organ rejection. These functional and structural deficits have inspired strategies for lymphatic vasculature modulation and tissue engineering to regulate immune functions during disease and injury rehabilitation. Lymphangiogenesis-the process of lymphatic vessel growth- is central to the success of these strategies and has broad potential if harnessed for therapeutic intervention and tissue integration. Here we review the opportunities and obstacles for biomolecular pathway modulation, nanotechnology, and tissue engineering to promote or inhibit lymphangiogenesis.