AR Tzafriri, A-M Spognardi, P Markham, JH Keating, MW Kayo, S Karamdoust, A Pollit, A Raval, R Mandal. ‘Mechanistic Kinetic Modeling Of Polymer Bioresorption Can Derisk The Preclinical Safety Evaluation Of Bioresorbable Polymer Coated Stents.’ Presented at: CRT 2026.
Background: Slow bioresorbing polymeric stent coatings reduce tissue exposure to potentially proinflammatory erosion by-products, yet necessitate preclinical evaluation down to trace residual polymer levels, adding development delays and costs.
Methods: Cobalt chromium stents coated with coating comprised of Poly Vinyl Pyrrolidone, Poly-L-Lactide-co-Caprolactone, and Poly-L-Lactide (Supraflex Cruz, Sahajanand Medical Technologies, India) were implanted into porcine coronary arteries (up to n=3/pig, balloon:artery=1.05-15:1). Stented arteries were excised post sacrifice and either analyzed for polymer molecular weight (MW) and polymer quantity using Gel Permeation Chromatography (GPC) with refractive index detection (RI), or histologically stained and scored for the presence of polymer coating by a boarded pathologist on a scale of 0 (absence) to 4 (high incidence). A mechanistic computational model was validated against GPC results of polymer MW and quantity through 12-months and then used to predict terminal bioresorption and then determine later timepoints.
Results: GPC-RI of stented artery extracts effectively separated and quantified polymer chains at MW of ~5000-150,000 Daltons (Da) and exhibited polymer peaks that were clearly distinguishable from biological material peak through 9 months. The polymer peak at 5000 Da began to co-elute with biological materials at 12 months, becoming indistinguishable in signal intensity from biological material at later times. At 12 months the co-eluting biological material was estimated at up to 10% of the overall 5000 Da peak height. As such, the 12-month timepoint was the last analytical value used in fitting a mechanistic kinetic model of polymer scission and mass bioresorption. Extrapolation of the best-fit bioresorption model predicted a decline of residual polymer from 29.4% at 12 months to 10.8% at 18 months, 0.2% at 24 months and 0.00% at 27 months. Median histopathology scores for coating presence showed good concordance with GPC and modeling, dropping from 2 at 1-3 months to 1 between 6-19 months and to 0 at 24-30 months.
Conclusions: Model-based extrapolation of GPC measured polymer masses showed high concordance with histopathology scores, offering a novel
Presented at Cardiovascular Research Technologies (CRT), 2026 March 7-10, Washington DC.