Development of Semicrystalline Morphology of Poly(L-lactic Acid) during Processing of a Vascular Scaffold

New and promising treatments for coronary heart disease are enabled by vascular scaffolds made of poly(L-lactic acid) (PLLA), as demonstrated by Abbott Vascular’s bioresorbable vascular scaffold. PLLA is a semicrystalline polymer whose degree of crystallinity and crystalline microstructure depend on the thermal and deformation history during processing. In turn, the semicrystalline morphology determines scaffold strength and biodegradation time. However, spatially-resolved information about the resulting material structure (crystallinity and crystal orientation) is needed to interpret in vivo observations. The first manufacturing step of the scaffold is tube expansion in a process similar to injection blow molding. Spatial uniformity of the tube microstructure is essential for the consistent production and performance of the final scaffold. For implantation into the artery, solid-state deformation below the glass transition temperature is imposed on a laser-cut subassembly to crimp it into a small diameter. Regions of localized strain during crimping are implicated in deployment behavior. To examine the semicrystalline microstructure development of the scaffold, we employed complementary techniques of scanning electron and polarized light microscopy, wide-angle X-ray scattering, and X-ray microdiffraction. These techniques enabled us to assess the microstructure at the micro and nano length scale. The results show that the expanded tube is very uniform in the azimuthal and axial directions and that radial variations are more pronounced. The crimping step dramatically changes the microstructure of the subassembly by imposing extreme elongation and compression. Spatial information on the degree and direction of chain orientation from X-ray microdiffraction data gives insight into the mechanism by which the PLLA dissipates the stresses during crimping, without fracture. Finally, analysis of the microstructure after deployment shows that it is inherited from the crimping step and contributes to the scaffold’s successful implantation in vivo.</p

Methods and systems for synthesis of an ultra high molecular weight polymer

A method for controlling the physical state of an ultra-high molecular weight polymer to make the ultra-high molecular weight polymer suitable for further processing, and related polymers compositions methods and systems, wherein the method comprises combining a catalyst, monomers, and an additive, for a time and under condition to allow synthesis of a nascent polymer and eo-crystallization of the nascent polymer with the additive

Multiplicity of morphologies in poly (L-lactide) bioresorbable vascular scaffolds

Poly(L-lactide) (PLLA) is the structural material of the first clinically approved bioresorbable vascular scaffold (BVS), a promising alternative to permanent metal stents for treatment of coronary heart disease. BVSs are transient implants that support the occluded artery for 6 mo and are completely resorbed in 2 y. Clinical trials of BVSs report restoration of arterial vasomotion and elimination of serious complications such as late stent thrombosis. It is remarkable that a scaffold made from PLLA, known as a brittle polymer, does not fracture when crimped onto a balloon catheter or during deployment in the artery. We used X-ray microdiffraction to discover how PLLA acquired ductile character and found that the crimping process creates localized regions of extreme anisotropy; PLLA chains in the scaffold change orientation from the hoop direction to the radial direction on micrometer-scale distances. This multiplicity of morphologies in the crimped scaffold works in tandem to enable a low-stress response during deployment, which avoids fracture of the PLLA hoops and leaves them with the strength needed to support the artery. Thus, the transformations of the semicrystalline PLLA microstructure during crimping explain the unexpected strength and ductility of the current BVS and point the way to thinner resorbable scaffolds in the future

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

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

Morphological variations in poly (L-Lactic Acid) (PLLA) vascular scaffolds for the treatment of coronary heart disease (CHD)

Poly (L-lactic Acid) (PLLA) is a semicryst. and biocompatible polymer that is used in bioresorbable vascular scaffolds for the treatment of Coronary Heart Disease (CHD). To treat CHD, a PLLA scaffold is deployed in the occluded artery to restore blood circulation. Implants made of PLLA undergo hydrolysis to form L-lactic acid that is readily metabolized by the human body, allowing them to harmlessly disappear in two years. The polymer is subjected to tube expansion and laser cutting before it is crimped onto a balloon. When the crimped scaffold is in position in the diseased artery, the balloon is inflated to deploy the scaffold. The resulting semicryst. structure changes over distances of a few microns, requiring X-ray microdiffraction to shed light on the structural changes that occur in PLLA vascular scaffolds which govern their therapeutic function. Crimping places the outer bend (OB) of a U-crest under elongation and the inner bend (IB) under compression. X-ray diffraction patterns indicate highly oriented PLLA crystallites where elongation was imposed (near the OB) and crystallites tilted out of plane where compression was imposed (at the IB). Between the IB and the OB, there is an unperturbed region with an orientation similar to the expanded tube. Deployment profoundly alters the structure created during crimping. The tilting of crystallites at the IB during crimping allows them to gracefully sep. into diamond shaped voids when the IB is placed under tension during deployment. Consequently, the OB experiences relatively mild compressive stress during deployment and a highly uniform structure is obsd. Despite PLLA's reputation as a brittle plastic, the solid state deformation does not fracture the scaffold; rather, the deployed PLLA scaffold has a high degree of orientation, giving the scaffold the radial strength to hold the blood vessel open