Crimping-induced structural gradients explain the lasting strength of poly l-lactide bioresorbable vascular scaffolds during hydrolysis.

Biodegradable polymers open the way to treatment of heart disease using transient implants (bioresorbable vascular scaffolds, BVSs) that overcome the most serious complication associated with permanent metal stents-late stent thrombosis. Here, we address the long-standing paradox that the clinically approved BVS maintains its radial strength even after 9 mo of hydrolysis, which induces a ∼40% decrease in the poly l-lactide molecular weight (Mn). X-ray microdiffraction evidence of nonuniform hydrolysis in the scaffold reveals that regions subjected to tensile stress during crimping develop a microstructure that provides strength and resists hydrolysis. These beneficial morphological changes occur where they are needed most-where stress is localized when a radial load is placed on the scaffold. We hypothesize that the observed decrease in Mn reflects the majority of the material, which is undeformed during crimping. Thus, the global measures of degradation may be decoupled from the localized, degradation-resistant regions that confer the ability to support the artery for the first several months after implantation.

Tungsten disulfide nanotubes enhance flow-induced crystallization and radio-opacity of polylactide without adversely affecting in vitro toxicity.

Treatment of vascular disease, from peripheral ischemia to coronary heart disease (CHD), is poised for transformation with the introduction of transient implants designed to "scaffold" regeneration of blood vessels and ultimately leave nothing behind. Improved materials could expand the use of these devices. Here, we examine one of the leading polymers for bioresorbable scaffolds (BRS), polylactide (PLA), as the matrix of nanocomposites with tungsten disulfide (WS2) nanotubes (WSNT), which may provide mechanical reinforcement and enhance radio-opacity. We evaluate in vitro cytotoxicity using vascular cells, flow-induced crystallization and radio-opacity of PLA-WSNT nanocomposites at low WSNT concentration. A small amount of WSNT (0.1 wt%) can effectively promote oriented crystallization of PLA without compromising molecular weight. And radio-opacity improves significantly: as little as 0.5 to 1 wt% WSNT doubles the radio-opacity of PLA-WSNT relative to PLA at 17 keV. The results suggest that a single component, WSNT, has the potential to increase the strength of BRS to enable thinner devices and increase radio-opacity to improve intraoperative visualization. The in vitro toxicity results indicate that PLA-WSNT nanocomposites are worthy of investigation in vivo. Although substantial further preclinical studies are needed, PLA-WSNT nanocomposites may provide a complement of material properties that may improve BRS and expand the range of lesions that can be treated using transient implants. STATEMENT OF SIGNIFICANCE: Bioresorbable Scaffolds (BRSs) support regeneration of arteries without permanent mechanical constraint. Poly-L-lactide (PLLA) is the structural material of the first approved BRS for coronary heart disease (ABSORB BVS), withdrawn due to adverse events in years 1-3. Here, we examine tungsten disulfide (WS2) nanotubes (WSNT) in PLA to address two contributors to early complications: (1) reinforce PLLA (enable thinner BRS), and (2) increase radiopacity (provide intraoperative visibility). For BRS, it is significant that WSNT disperse, remain dispersed, reduce friction and improve mechanical properties without additional chemicals or surface modifications. Like WS2 nanospheres, bare WSNT and PLA-WSNT nanocomposites show low cytotoxicity in vitro. PLA-WSNT show enhanced flow-induced crystallization relative to PLA, motivating future study of the processing behavior and strength of these materials.

Interaction of Poly L-Lactide and Tungsten Disulfide Nanotubes Studied by in Situ X-ray Scattering during Expansion of PLLA/WS2NT Nanocomposite Tubes.

In situ synchrotron X-ray scattering was used to reveal the transient microstructure of poly(L-lactide) (PLLA)/tungsten disulfide inorganic nanotubes (WS2NTs) nanocomposites. This microstructure is formed during the blow molding process ("tube expansion") of an extruded polymer tube, an important step in the manufacturing of PLLA-based bioresorbable vascular scaffolds (BVS). A fundamental understanding of how such a microstructure develops during processing is relevant to two unmet needs in PLLA-based BVS: increasing strength to enable thinner devices and improving radiopacity to enable imaging during implantation. Here, we focus on how the flow generated during tube expansion affects the orientation of the WS2NTs and the formation of polymer crystals by comparing neat PLLA and nanocomposite tubes under different expansion conditions. Surprisingly, the WS2NTs remain oriented along the extrusion direction despite significant strain in the transverse direction while the PLLA crystals (c-axis) form along the circumferential direction of the tube. Although WS2NTs promote the nucleation of PLLA crystals in nanocomposite tubes, crystallization proceeds with largely the same orientation as in neat PLLA tubes. We suggest that the reason for the unusual independence of the orientations of the nanotubes and polymer crystals stems from the favorable interaction between PLLA and WS2NTs. This favorable interaction leads WS2NTs to disperse well in PLLA and strongly orient along the axis of the PLLA tube during extrusion. As a consequence, the nanotubes are aligned orthogonally to the circumferential stretching direction, which appears to decouple the orientations of PLLA crystals and WS2NTs.

Tube Expansion Deformation Enables In Situ Synchrotron X-ray Scattering Measurements during Extensional Flow-Induced Crystallization of Poly l-Lactide Near the Glass Transition.

Coronary Heart Disease (CHD) is one of the leading causes of death worldwide, claiming over seven million lives each year. Permanent metal stents, the current standard of care for CHD, inhibit arterial vasomotion and induce serious complications such as late stent thrombosis. Bioresorbable vascular scaffolds (BVSs) made from poly l-lactide (PLLA) overcome these complications by supporting the occluded artery for 3⁻6 months and then being completely resorbed in 2⁻3 years, leaving behind a healthy artery. The BVS that recently received clinical approval is, however, relatively thick (~150 µm, approximately twice as thick as metal stents ~80 µm). Thinner scaffolds would facilitate implantation and enable treatment of smaller arteries. The key to a thinner scaffold is careful control of the PLLA microstructure during processing to confer greater strength in a thinner profile. However, the rapid time scales of processing (~1 s) defy prediction due to a lack of structural information. Here, we present a custom-designed instrument that connects the strain-field imposed on PLLA during processing to in situ development of microstructure observed using synchrotron X-ray scattering. The connection between deformation, structure and strength enables processing⁻structure⁻property relationships to guide the design of thinner yet stronger BVSs.

Controlled nucleation and growth of CdS nanoparticles in a polymer matrix.

In-situ synchrotron X-ray diffraction (XRD) was used to monitor the thermal decomposition (thermolysis) of Cd thiolates precursors embedded in a polymer matrix and the nucleation of CdS nanoparticles. A thiolate precursor/polymer solid foil was heated to 300 degrees C in the X-ray diffraction setup of beamline W1.1 at Hasylab, and the diffraction curves were each recorded at 10 degrees C. At temperatures above 240 degrees C, the precursor decomposition is complete and CdS nanoparticles grow within the polymer matrix forming a nanocomposite with interesting optical properties. The nanoparticle structural properties (size and crystal structure) depend on the annealing temperature. Transmission electron microscopy (TEM) and photoluminescence (PL) analyses were used to characterize the nanoparticles. A possible mechanism driving the structural transformation of the precursor is inferred from the diffraction features arising at the different temperatures.