Natural Vascular Scaffolding Treatment Promotes Outward Remodeling During Arteriovenous Fistula Development in Rats

• DOI: 10.3389/fbioe.2021.622617
• Publication Date: 2021-02-16T05:26:17Z
• Authors: Yan-Ting Shiu; Yuxia He; Jason C. S. Tey; Marina Knysheva; Blake Anderson; Katalin Kauser
• Keywords: Lumen (anatomy); Femoral vein

Following creation, an arteriovenous fistula (AVF) must mature (i.e., enlarge lumen to allow high blood flow) before being used for hemodialysis. AVF maturation failure rates are high, and currently, there no effective therapy treat this problem. The process is likely affected by the integrity of vascular extracellular matrix (ECM). Natural Vascular Scaffolding (NVS) Therapy a new technology that interlinks collagen elastin via photoactivation locally delivered small molecule (4-amino-1,8-naphtalamide). We hypothesized NVS may improve remodeling preserving ECM integrity. AVFs were created in Wistar male rats connecting femoral vein (end) artery (side) same limb. Immediately after flow was restored dilate arterial pressure, 10 μl-drop compound (2 mg/ml) placed on anastomosis perivascularly. 5-min incubation, treated area exposed 1-min illumination 450-nm light. control group received phosphate buffered saline (PBS) light activation. skin closed, euthanized 4 weeks ( n = 6–9 per group) post-AVF creation histology, morphometry, immunohistochemistry (IHC), multiphoton microscopy second-harmonic-generation evaluation fibers. thickness similar both groups. vein’s open % NVS-treated significantly larger than PBS-treated (4.2-fold p 0.014 2-fold 0.009, respectively). inflammatory markers IL-6 MMP-9 walls decreased PBS group. Collagen fibers wall trended toward perpendicular alignment circumference AVFs, with more defined shape but less AVFs. These results indicate exerted changes collagen, which influence maturation. Rats tolerated treatment well, lack cell death confirmed culture experiments. suggest safe have therapeutic potential facilitating expansion enhanced patients.