Bioresorbable stent scaffolds are balloon-expandable and have been used to replace metallic stents to treat the narrowing of arteries and airway passages. Like traditional metallic scaffolds, bioresorbable scaffolds provide artery and/or airway support and act as a delivery system for the controlled release of an anti-inflammatory drug to prevent narrowing of the vessel lumen. Unlike metallic scaffolds that are permanent, bioresorbable scaffolds degrade over time and are completely absorbed and eliminated from the body after they are implanted, and therefore eliminate the need for additional surgical procedures. Bioresorbable scaffolds are used in coronary, peripheral, neural, and nasal applications. Each application has different scaffold sizes (OD and wall thicknesses), vessel support requirements, and degradation times.
Bioresorbable polymers, such as poly-L-lactide (PLLA) and polylactic-co-glycolic acid (PLGA), are used for stent scaffolds and other medical applications such as resorbable sutures, ligament tissue, orthopedic implants, and controlled drug delivery systems. Both PLLA and PLGA degrade by hydrolysis, which is the chemical breakdown of the compound due to the reaction with water. The glass transition temperature (Tg) of both PLLA and PLGA is higher than the normal body temperature of 37°C, which allows the polymers to remain rigid and resistant to short-term creep deformation after implantation.
PLLA and PLGA are high molecular weight polymers. For example, a common PLLA used for a coronary scaffold has inherent viscosity (IV) of 3.8 dl/g compared to PET, which may have an IV of .75 dl/g. PLLA is a semi-crystalline biocompatible homopolymer supplied in granule form that has high mechanical strength ideal for extruded bioresorbable coronary stent scaffolds. Typical PLLA used for scaffolds has a melt temperature (Tm) of 180° to 190°C (356° to 374°F) and is heated to 200° to 210°C (390° to 410°F).
PLGA is a biocompatible copolymer that is commonly used for nasal scaffold implants and suture applications. PLGA devices degrade faster than their corresponding PLLA devices, which also have greater mechanical properties.
In addition to PLLA and PLGA bioresorbable polymers for scaffolds, the surface of the scaffold is coated with a bioresorbable polymer and a drug that is released over time to prevent restenosis (narrowing of the stent lumen). Poly-DL-lactic acid (PDLLA), which is an amorphous (non-crystalline) polymer, is used as a carrier of controlled-release anti-inflammatory drugs, such as Everolimus or Sirolimus, that prevent restenosis.
Bioresorbable stent scaffolds are manufactured from PLLA and PLGA polymers that are extruded into tight tolerance tubing that is secondarily radially and axially expanded, and laser machined into a scaffold pattern. Additional processes include surface coating the scaffold with a bioresorbable polymer that carries a drug, adding radio-opaque marker bands on each end, crimping the stent to the balloon catheter delivery system, and radiation sterilization.
Processing bioresorbable materials for implants is typically done in a cleanroom environment with current Good Manufacturing Practices (cGMP). cGMP requirements involve the maximum use of stainless steel, special material selections, and all surfaces that come in contact with the product must be smooth and without any raised or recessed points where materials can be trapped and degrade. The cGMP requirements for processing bioresorbable materials are typically not as stringent as the requirements for pharma applications.
Mechanical Properties and Molecular Weight
Critical to the functionality of a PLLA scaffold are certain mechanical properties, mainly a high radial strength for vessel support and to resist inward recoil of the scaffold after implantation within a desired time. (See Figure 1) The scaffold must also be flexible enough to be delivered distally into the artery via balloon expansion without fracturing the struts of the scaffold. PLLA is brittle and scaffolds have been known to have strut fracture due to over-dilation during balloon expansion. For this reason, PLLA copolymers have been developed that are strong but more ductile to prevent fracture during excessive balloon expansion.
The mechanical properties of the PLLA and PLGA scaffolds are greatly reduced by thermal degradation of the polymer and molecular weight loss caused from excessive thermal history (temperature and time) during the extrusion process. Moisture content prior to extrusion and secondary exposure to e-beam or gamma radiation sterilization also has an impact on molecular weight loss. The molecular weight (Mn) of polymers determines the mechanical properties of polymers and it is measured in Daltons (Da). The Mn is greatly reduced during the manufacturing process by more than 70 percent, depending on the moisture content prior to extrusion, the thermal history during extrusion, and the radiation dose applied after extrusion.
Keys to Optimizing Extruded Scaffold Tubing
The higher the thermal history during extrusion of the tubing, the greater the decrease in Mn, and decrease in the time that the radial strength of the scaffold is effective. Therefore it is critical to minimize the residence time and process temperatures during extrusion of bioresorbable resins to maximize absorption time and the radial strength of the extruded PLLA tubing. PLLA has often been processed on 19mm (¾") and 25mm (1") extruders but this is not recommended due to thermal degradation caused by excessive residence time with an over-sized extruder. For future scaffold developments, PLLA should ideally be extruded on micro extruders in the 12mm to 16mm screw size range. Extruding a 2.5mm (0.098") OD x 150μm (0.006") wall thickness tube from a PLLA resin on a 19mm (3/4") extruder at 5-10 RPM screw speed will result in a residence time of 8 to 10 min. Extruding the same PLLA tube on a 12mm micro extruder at 15 to 20 RPM screw speed will result in a residence time of 5 minutes or less.