Electrospun Short Fibers With Loaded Astragaloside And Ferulic To Promote Angiogenesis In Ischemic Tissues

Due to unhealthy eating habits and ageing of the population, the incidence of limb ischemic diseases increased year by year and has gradually become a serious threat to human health and life. Limb ischemic diseases are caused by atherosclerosis or vascular occlusion, and early characterized by intermittent claudication. The critical limb ischemia patient will be resting pain, ischemic ulcer and gangrene, even leading to amputation and death of patients. The current main methods in the clinical treatment of ischemic diseases include vascular bypass surgery, lumen interventional therapy and drug therapy. Although these methods can alleviate ischemic symptoms to some extent, but they suffer from insufficient and impermanent treatment effect. Electrospun fibers shows advantages in the wide selection of materials, adjustable physics performance, and controllable release of active ingredients and indicates potentials to promote the regeneration and maturation of blood vessels. But electrospun fibers should be implanted into tissues to induce the formation of blood vessels. Thus, in the current study polymer short fibers with different aspect ratios were prepared, and short fibers with loaded astragaloside IV (AT) and ferulic acid (FA) were subjected to injected locally into ischemic tissues. The distribution of short fibers with different aspect ratios and their retention in ischemic tissues were evaluated to explore the treatment efficacy on ischemia. We need to explore a more effective solution to promote vascularization and restore blood supply of ischemic tissues.Short fibers were obtained with average diameter of1μm and the aspect ratios of7.1,22.9and76.4through frozen section of aligned electrospun fibers. The injectability of short fibers were associated with their aspect ratios, and a better injectability was achieved to fibers with smaller aspect ratios. In vitro release study indicated both of AT and FA can steady release from the short fibers, indicating releasing behaviors similar to those from electrospun fibrous mats. In vitro evaluation on both vascular endothelial cells (EC) and smooth muscle cells (SMC) showed that all the short fibers promote cell proliferation and secretion of extracellular matrices, indicating no significant difference compared with electrospun fibrous mats. In vivo distribution experiment indicated that short fibers were mainly retained within the injection area, and few of them were distributed in other organs dependent on the aspect ratios of short fibers. On the basis of the injectability and retention capabilities, short fibers with an aspect ratio of20were chosen for subsequent investigation on in vivo efficacy. Murine models of stable hindlimb ischemia of moderate degree were established, then the short fibers was injected into ischemia muscle. Results indicate that drug-loaded short fibers could decrease the limb loss rate, promote the recovery of blood perfusion within ischemic tissue, reduce the fibrosis area of ischemia muscle. The effect of drug-loaded short fibers on the promotion of angiogenesis and vascular mature was more significant than drug-loaded fiber mats or other groups. These results indicated that the drug-loaded short fibers with low invasiveness and high tissue repair enhancement should have great potential for therapeutic angiogenesis in ischemic tissues.