Fabrication of polymer blend vascular grafts with enhanced mechanical properties and rapid cell infiltration: influence of micro/nanostructure, polymer composition, and post-processing on pore architecture and bioengineered environment.

Arteriovenous (AV) shunts are critical conduits for patients with end-stage renal disease undergoing hemodialysis. Desired properties of next-generation AV graft materials include artery-like mechanics, clinically feasible manufacturing processes, and a bioactive interface that facilitates rapid and deep infiltration of neighboring cells to support tissue regeneration. These requirements inspired the design, fabrication, and post-processing of our constructs. In terms of material design, we evaluated the performance of three microfiber graft materials composed of a hydrophobic polymer and photo-clickable, 4-arm thiolated polyethylene glycol-norbornene (PEG-NB). The materials included two coaxially nanostructured fiber designs, each featuring a PEG-NB sheath and different cores-polycaprolactone (PCL) and PCL-co-lactic acid (PLCL), respectively-and a mixed composition created by directly blending the sheath and core solutions during electrospinning. For post-processing, the constructs were either air-dried or freeze-dried (FD). Surface morphology was assessed using scanning electron microscopy, while mechanical properties were characterized through tensile testing and dynamic mechanical analysis. Subcutaneous implants were evaluated at 1, 4, and 16 weeks using histological, immunofluorescent, and multiphoton microscopy analyses to examine cellular distribution, material structure, and tissue remodeling. Results showed that the freeze-drying post-processing method enhanced overall porosity, stiffness, and ultimate tensile strength. Among all tested conditions, the FD core-sheath structure with PCL most closely matched the mechanical properties of native vessels. Using PLCL as a core material increased degradation and cell infiltration during the first month of subcutaneous studies. Ultimately, graft strength, porosity, and bioactivity were effectively modulated by the choice of core material and post-processing method. These findings provide insights into tailoring electrospun PEG-NB hybrid constructs as candidate AV shunt grafts, highlighting opportunities to balance mechanical performance, degradation, and bioactivity for end-stage renal disease patients requiring durable hemodialysis access.