Bioresorbable Coronary Scaffolds

Polymers

The term “polymer” originates from the Greek words «πολύ» (many or much = poly) and «μέρος» (part = mer) and refers to a macro-molecule that is composed of multiple repeated sub-units. Polymers have specific characteristics that define their mechanical properties which in turn define their suitability to be used as materials for scaffold development. Copolymerization of polymers with different properties has been widely employed in BRS fabrication to overcome the individual weaknesses of each polymer. The key polymer characteristics, beyond their type, include molecular weight, crystallinity, and hydrophobicity, while the key mechanical properties are tensile strength, elasticity, phase behavior, and biodegradation rate. The weight-averaged molecular weight of the polymer affects its processability whereas the number-averaged molecular weight influences its mechanical strength and elasticity. Crystallinity is determined by the degree of monomers’ linear arrangement and affects both tensile strength and degradation rate; in general, higher crystallinity results in longer degradation time and higher tensile strength. Hydrophobicity , from the Greek word «ύδωρ» = hydro (water) and «φόβος» = phobia, is the property of repelling water rather than absorbing it or dissolving in it and is also a regulating factor of the degradation rate. Tensile strength quantifies the amount of stress that a material can endure before suffering permanent deformation. Good radial strength allows for thinner struts and lower profile, hence better deliverability. Elasticity, from the Greek word «ἐλαστός» = ductible, is defined as the ability of a body to resist a distorting/deforming influence or force and return to its original size and shape when the latter is removed. For polymers, their elastic properties are quantified by the Young’s or tensile modulus of elasticity which is highly dependent on temperature. In the case of PLLA, increasing crystallinity is expected to increase its strength but at the expense of reducing its elasticity, limiting the amount of expansion that a polymer scaffold can endure during deployment without fracturing. The phase behavior of polymers is defined by their glass transition temperature (Tg) (= the temperature that the polymer starts to display rubbery behavior) and melting point temperature (Tm).

Poly(Aliphatic-Esters)

Pure poly(lactic acid) (PLA) has unfavorable mechanical properties for BRS production but exists as two stereo-isomers that result in four distinct polymers, namely PLLA, poly(D-lactic acid) or PDLA, poly(D,L-lactic acid) or PDLLA, and meso-PLA. The first three have favorable characteristics for BRS fabrication. PLLA is a semi-crystalline material that consists of highly ordered segments with high concentrations of polymer, termed crystal lamellae, bound together by less dense, amorphous polymer tie chains. It has high tensile strength, although still inferior to the durable metals used in conventional stent fabrication, while the additional methyl group makes it more hydrophobic, leading to slower absorption rates than non-PLA-related polymers. Furthermore, it is less inflammatory and has the highest Tg among the general biodegradable polymers, well above the body temperature of 37 ^o C, so that the scaffold is dimensionally stable in its deployed size under physiological conditions. For these reasons, PLLA is the most commonly used polymer for BRS fabrication. The degradation of PLLA takes place in three steps. First, hydrolysis of the amorphous regions, which are less packed and therefore more accessible to water, occurs. The molecular weight decreases, with little effect on mechanical performance and a slight reduction in crystallinity. In the second phase, continuous cleavage of the amorphous tie chains occurs, which causes a decrease in mechanical strength (due to scission of the amorphous tie chains) and polymer fragmentation into low-weight oligomeric poly-lactic acid molecules. This results in further mass loss and visible structural discontinuities. Finally, the oligomers hydrolyze to lactic acid monomers which de-protonate to lactate. Lactate is then converted to pyruvate and enters the Krebs cycle, where it is further metabolized in CO ₂ and H ₂ O excreted through the lungs and kidneys, respectively. Remaining particles smaller than 2 μm are phagocytosed by macrophages. In practice, since the degradation rate depends on a number of more or less interrelated factors, there is not one PLLA but a number of polymers having the same basic chemical structure but different behaviors depending on the synthesis route. PDLA is a crystalline material with similar physico-chemical and hydrolytic properties to PLLA, although somewhat lower tensile strength and stiffness. However, the derived polymer has not been exploited so far, primarily because the D-lactic acid precursor is less accessible than the L-isomer. PDLLA is an amorphous polymer, due to the random distribution of the two isomeric forms of PLA that it contains, it and has a lower tensile strength and a shorter degradation rate than PLLA. Poly(glycolic acid) (PGA) is the simplest linear aliphatic polyester and one of the first biodegradable polymers ever investigated for medical use. It has the highest tensile strength among the polymers used for BRS fabrication, but it also has a rapid degradation rate and an increased inflammatory trend. Polycaprolactone (PCL) is a semi-crystalline polymer with very high elongation at break but very low in vivo degradation rate. The structural changes during the bioresorption process of three characteristic BRS based on aliphatic polyesters are shown in Fig. 16.1 .