Mechanical Characterization of Poly(vinyl alcohol) and Resorcinol Diphenyl Phosphate Clay Blend Vascular Grafts

Poly(vinyl alcohol) is suitable for vascular grafts in patients due to its biocompatibility and tunable mechanical properties, but its documented bioinert nature limits cell-adhesiveness, which is critical for the long-term patency of grafts in vivo [1]. We have previously found that Resorcinol Diphenyl Phosphate (RDP)-clay, a phosphate ester flame retardant, can enhance mechanical and cell-adhesive properties when blended with other polymers[2]. Here, we report on the effect of RDP-clay on the mechanical properties of PVA hydrogels towards manufacture of small-diameter vascular grafts.<br/>PVA/RDP-clay blend solutions were synthesized by combining 10% PVA (w/w) solution with RDP-clay at 0%, 1%, 5%, and 10% (w/w), respectively. These solutions were crosslinked with 15% (w/w) sodium trimetaphosphate (STMP) and 30% (w/w) sodium hydroxide (NaOH). This solution was poured into 26mm diameter molds and allowed to dry overnight, after which the resulting discs were rehydrated in Dulbecco’s Phosphate Buffered Saline (DPBS) for about 24 hours. Rheology of these discs was characterized using a Kinexus Pro+ rheometer (Netzsch), with oscillatory amplitude sweeps with parameters 0.1 to 100 Pa range, 1 Hz frequency, and 25 C temperature.<br/>To create small-diameter grafts from this polymer blend, we devised a 3-step process. Melted wax was injected into a metal tube and allowed to harden, creating a 2 mm diameter wax rod. For all RDP-clay concentrations, these rods were affixed to a single-axis spinner and dipped 10 times in PVA blend, with 15 minutes of spin-drying between dips. After the final dip, rods were allowed to spin-dry overnight, rehydrated the next day, and the wax rods were removed to obtain patent vascular grafts. These grafts were orthogonally cut into thin rings, allowing wall thickness measurements to be found using a Keyence VHX-7000 microscope. 2 cm lengths of vascular graft tubes were also orthogonally cut, then attached to a PG-5 Digital Pressure Gauge and pressurized until rupture to determine vessel burst pressure.<br/>Blend characterization through rheology indicated an average modulus of 35 kPa, with a slight increase as RDP-clay concentration increased. The described manufacture method for these small-diameter grafts was successful at creating patent vessels at all RDP-clay concentrations tested. Vessel thickness was significantly larger in 10% RDP-clay vessels than in 0%, 1% and 5%. 10% RDP-clay vessels were also visibly less smooth and homogenous than lower RDP-clay concentration vessels. Burst pressures were greater than physiological values for all RDP-clay concentrations (200-700 mmHg), but 10% RDP-clay vessels were more prone to pin-prick bursts. As such, we posit that 10% RDP-clay may be an upper limit for organoclay additive concentration to maintain mechanical integrity of the PVA hydrogel.<br/>The mechanical properties of the PVA/RDP-clay blends under these manufacture and processing techniques show great promise for use as vascular grafts in patients. Future steps include characterizing endothelial cell adhesion and proliferation within these manufactured vessels as well as better controlling drying time between dips during manufacture to attain consistent wall thickness.<br/><br/><br/>[1] Conconi, M. T., et al. (2014). Molecular Medicine Reports.<br/>[2] Feng et al. MRS Fall Meeting; 2018 Nov 25-30; Boston, USA.