Abstract Background Diabetic ulcers are characterized by local ischemia, usually without macroangiopathy. We have previously found that the combination of VEGF and PDGF-BB in a fibrin matrix is effective in stimulating arterial growth to diabetic wounds. Aims We developed modified forms of VEGF and PDGF-BB to bear super-affinity for the extracellular matrix (SA-VP), in order to decorate the wound tissue without the need for a biomaterial. We investigated the dose-dependent effects on local blood flow and wound healing, by applying the treatment either to the healthy tissue around the wound or to the damaged wound bed. Methods Full thickness wounds were created on the dorsal skin of diabetic (db/db) mice. SA-VP or saline were applied to the wound bed or divided into 4 injections around the wound edge. Wound closure and blood flow were measured on days 4 and 8 after treatment and tissues were harvested for histology on day 8. Data were analysed by Anova with Tukey’s post-hoc test for multiple comparisons. Results Wound healing was improved dose-dependently by SA-VP by both delivery routes. Histologically, angiogenic areas and total amount of angiogenesis were significantly increased by the highest SA-VP dose, again independent of delivery route (p = 0.034). However, the total amount of recruited arterioles was significantly increased only in the healthy tissue around the wound and only by intradermal injections of SA-VP (p = 0.008). In agreement with the arteriogenic effect, the blood flow at day 4 was significantly increased only by injections of the highest SA-VP dose around the wound (p = 0.018). Conclusion SA-VP treatment significantly accelerates wound healing in a diabetic murine model with a clear dose-dependent effect. Targeting the undamaged tissue around the wound by injections induces more effective arteriogenesis. However, direct treatment of the wound bed is equally effective for healing. These results support further development for a potential clinical use.