Therapeutic Treatment with Sustained-Release Platelet-Rich Plasma Restores Blood Perfusion by Augmenting Ischemia-Induced Angiogenesis and Arteriogenesis in Diabetic Mice

Abstract

Objective: The objective of this investigation was to establish the effectiveness of sustained-release platelet-rich plasma (PRP) on perfusion and neovascularization in diabetic murine hind limb ischemia. Methods: After surgery in streptozotocin-induced diabetic mice, the mice were randomly assigned to the following 4 experimental groups: control (C), 100 µl of the sustained-release form of platelet-poor plasma (PPP), 100 µl of the solution form of PRP (PRP-sol), and 100 µl of the sustained-release form of PRP (PRP-sr). Endpoint evaluations were: blood perfusion by laser Doppler perfusion imaging (LDPI), vascular density by anti-vWF, and mature vessel density by anti-smooth muscle actin antibody. Results: This study demonstrated that a sustained release of PRP increases the perfusion of ischemic tissue as measured by LDPI (57 ± 12; 56 ± 9; 72 ± 7, and 98 ± 4 for the C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05), capillary density (151 ± 16; 158 ± 12; 189 ± 39, and 276 ± 39 for groups C, PPP, PRP-sol, and PRP-sr, respectively; p < 0.05), and mature vessel density (28 ± 2; 31 ± 3; 52 ± 10, and 85 ± 13 for the C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05). Conclusion: A sustained release of PRP containing potent angiogenic growth factors restores blood perfusion by stimulating angiogenesis and arteriogenesis.