Immunomodulation and Mechanical Characterization of Manuka Honey-Incorporated Near-Field Electrospun Bioresorbable Vascular Grafts.

(1) Current synthetic small-diameter vascular grafts fail frequently due to anastomotic hyperplasia and thrombosis caused by mechanical mismatch and incomplete reendothelialization. Polydioxanone near-field electrospun (NFES) vascular templates feature programmable pore sizes to facilitate transmural ingrowth of endothelial cells and show promise in reducing mechanical mismatch, but their potential as drug delivery systems remains unexplored. It was hypothesized that Manuka honey incorporation in NFES templates could reduce neutrophil extracellular trap (NET) release but decrease mechanical strength. (2) Templates were fabricated using 90 mg/mL polydioxanone in 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) and Manuka honey concentrations of 0%, 0.1%, 1%, and 10% v/v. Wall thickness (197-236 μm), mechanical properties, Manuka honey elution, and NET release were quantified. (3) The 0.1% and 1% templates best mimicked native vessel mechanics, outperforming the pure HFP template in tensile strength and burst pressure. The 10% templates exhibited significant mechanical strength reductions. Manuka honey elution exhibited a burst release within the first three hours, and all honey was eluted by day three. NET release was elevated in 10% and control groups but was not significantly different from 0.1% and 1%. (4) Overall, low concentrations of Manuka honey maintained mechanical compatibility, but elution must be optimized for immunomodulation, rejecting the initial hypothesis.