Polymers and nanocomposites to treat vascular disease without a trace Julie Kornfield 1 , Artemis Ailianoua 1 , Jordan Barr 3 , Jude Cameron 3 , Giovanni De Filippo 2 , Tiziana DiLuccio 1 , Alex Lennon 3 , Sandy Leung 4 , Eimear Magee 4 , Tony McNally 4 , Gary Menary 3 , Riccardo Miscioscia 2 , Guiseppe Pandolfi 2 , Karthik Ramachandran 1 , Lison Rocher 3 , Fulvia Villani 2 , Huidong Wei 3 1 Caltech, USA, 2 ENEA-Portici, Italy, 3 Queens University of Belfast, UK, 4 University of Warwick, UK A wave of bioresorbable devices are being introduced to treat vascular disease in the heart and limbs. Biodegradable semicrystalline polymers provide the structural material of leading bioresorbable scaffolds (BRSs), a credit to innovative processing methods developed to achieve new combinations of strength, toughness and bioabsorption rates. With Abbott Vascular, we discovered that the key to resilient poly L-lactide (PLLA) lies in the interaction of two manufacturing steps—tube expansion and crimping. X-ray microdiffraction revealed that dramatic gradients of structure [1] created during crimping slow hydrolysis precisely where stress is concentrated, preserving strength where it is needed most. [2] Even after 9 months of hydrolysis in vitro, despite a 40% decrease in PLLA molecular weight, the BRS retains its initial strength. Clinical considerations motivate thinner devices that are visible in x-ray radiography during and after implantation. Toward the goal of stronger, radiopaque, bioresorbable materials, we explore PLLA reinforcement by inorganic nanotubes (NT) with strong x-ray absorbtion, specifically, tungsten disulfide (WS2). [3] The effects of WS2NT on PLLA crystallization reveal a new interaction between early processing steps in BRS manufacture (preform extrusion and tube expansion).[4] Innovative processing methods developed by biomedical device manufacturers give PLLA resilience to survive crimping, deployment and months of hydrolysis, fueling optimism that scaffolds will support arteries’ ability to heal, ultimately enabling recovery from vascular diseases without leaving a trace. Acknowledgements: Jim Oberhauser introduced me to BRS; Mary-Beth Kossuth (Abbott Vascular) was central to our work on Absorb. SAXS/WAXD at 5-ID-D DND-CAT at Advanced Photon Source (APS) at Argonne National Laboratory were enable by Steven Weigand. Funding: Abbott Vascular, Caltech Jacobs Institute (JIMEM), EU Horizon2020 MC-RISE # 691238, and NIH Heart, Lung, Blood Inst. # F31HL137308. References 1. Ailianou, A., Ramachandran, K., et al. (2016),"Multiplicity of morphologies in poly (L-lactide) bioresorbable vascular scaffolds," PNAS, 113, 11670-11675. 2. Ramachandran, K., et al. (2018), "Crimping-induced structural gradients explain the lasting strength of poly L-lactidebioresorbable vascular scaffolds during hydrolysis," PNAS, 115, 10239-10244. 3. Rocher, L., et al. (2021), "Interaction of Poly L-Lactide and Tungsten Disulfide Nanotubes Studied by In SituX-ray Scattering during Expansion of PLLA/WS2NT Nanocomposite Tubes,” Polymers, 13, Article Number1764. 4. Ramachandran, K., et al. (2022), "Tungsten disulfide nanotubes enhance flow-induced crystallization and radio-opacity of polylactide without adversely affecting in vitro toxicity," Acta Biomaterialia, 138, 313-326.
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