Radial Strength Study Of BioMagic Sirolimus-eluting Bioabsorbable Coronary Scaffold During In Vitro Degradation （6 Month Results）
By Robert Ndondo-Lay, Chief Technical Officer
Sterling Vascular Inc,
R&D Division of Shanghai BioMagic Medical Devices Ltd.
Shanghai International Medical Zone, Pudong,
Shanghai, China
Matt Irons, Techinician
Blockwise Engineering, LLC
425 S. 48th Street, Suite 108
Tempe, AZ 85281
Date: 12 Aug 2013
1.Background
Lactide based polymers, such as poly (L-Lactide) (PLLA), have been commonly used in a variety of resorbable medical devices such as in wound closure (1960s), orthopedic implants (1970s), controlled drug-releasing devices (1980s), vascular closing devices (1990s), and most recently, coro
nary scaffolds (2012).  These polymers can be readily engineered by material selection, design, and manufacture processing of the product to meet technical requirements for an implant device; they also have been proven to be safe materials with a long track record of in vivo biocompatibility for more than 30 years.
The poly (L-Lactide) (PLLA) polymers degrade through 5 stages [1]: (1) Hydration: polymer absorbs water from environment and water penetrates deeply into the interior of the implant. This is typical for a bulk-type of degradation; (2) Depolymerization / chemical cleavage of the polymer backbone. Hydrolysis is the basic mode of degradation since water reacts with the covalent bonds and segments the polymer chain into smaller polymer chains, decreasing the molecular weight; (3) Loss of mass integrity.  The loss of mass occurs when the implant essentially has no cohesive strength and the polymer starts to fragment into segments of low molecular weight polymer.  (4) Absorption.  Absorption via assimilation by phagocytes or further hydrolysis leads to soluble monomeric anions (such as L-lactate) which dissolves into the intercellular fluid; (5) Elimination.  The soluble L-lactate is converted into pyruvate, which enters the Krebs-cycle.
The major role of a PLLA-based implanted device is to perform a temporary mechanical function, allowing the tissue to heal and resume its original function, before the implanted device loses its mec
hanical integrity as it degrades over time gradually. In the case of drug coated coronary scaffold, its role is to provide mechanical support of a clogged artery up to the time that the newly formed endothelium cover the scaffold and during this period, allowing the drug to be released from the scaffold.  For this reason, it is of vital importance that the coronary scaffold will not lose its critical radial strength before healing has occurred.  This study is to determine how the degradation process affects the scaffold mechanical properties of BioMagic Bioabsorbable scaffold.
2. Study Objective
Sterling Vascular design goal of Biomagic Bioabsorbable Vascular scaffold (BVS) is to maintain radial strength of 350 mmHg for at least 90 days in vitro as indicated in the standard for metallic stents [3]. Radial strength test method is used to measure the pressure at which the scaffold experiences irrevocable deformation. The scaffold is subjected to circumferential compression in order to determine the maximum limit plastic deformation, which is reported as Radial Strength with “mmHg” as unit of measure.  The study objective is to determine the respective radial force of the BVS in vitro over time.
3. Equipment and Lab Supplies
⏹  BLOCKWISE RADIAL Force Tester
⏹  Optical Comparator  with Quadra-Check digital readout
⏹      Desktop computer with Software and HBLT software
⏹  Distilled water or equivalent or deionized water
⏹  Temperature controlled water bath
⏹      Polyethylene vials or  glass vials
⏹Recoil expansion block
⏹Cual expansion fixture to hold catheter during expansion
⏹Flick fixture
⏹Flat plate
⏹Expansion Block Holder
⏹Indeflator verified
⏹Post-dilatation catheters (0.5 mm larger than the label diameter of the scaffold with a balloon label length
at least 2 mm longer than the scaffold length)
⏹Timer with indicator os second
⏹Microscope with at least 10x
⏹Compressed air
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5.
(1)Sample Size Selection
In the BioMagic BVS product mix, the 3.0 x 28mm incorporates the same repeating elements compared to the 3.5 x 18mm device (identical end rings and body rings). In terms of diameter, BioMagic BVS of outer diameter (OD) of 2.5mm and of 3.0 mm use the same PLLA tubing except mounted on different balloon sizes; and 3.5mm uses larger tubing.  Therefore, the two diameters 3.0mm and 3.5mm are tested.
(2)Crimping Process
Crimping of polymer stents onto customer provided balloons previously crimped and expanded then re-pleated by a Blockwise Alpha Pleat Balloon Wrapping system.
Figure below shows the system used: CX crimper control unit with RJE62 crimping station and AS “Autosheathing” PTFE film protection option.
A: General Process Parameters
[Note: pre-crimp and crimp are separate processes]
Station beginning Dia. 4 mm for insertion / Dia. 3.5mm, 30 s hold @ 48 deg C thermal soak / pre-cri
mp dia.
1.45mm@ 0.03mm per second, hold 10 s / station open to 12mm for stent removal.
Station beginning dia. 2.0mm, 30 s hold @ 48 deg C thermal soak / “pillowing” step 1.5mm, balloon @ 13.8bar for 20 seconds / high force, varied 155-175 N surface pressure for 5 s/ reduced force, 50 N / repeat high-low force steps 3x total / remove product from station, cool 15 s / vacuum, 3 s / leak test 0.03 bar over 20 s test period
A sample size of 5 pcs was measured using a digital visual comparator at 79X magnification. The measured diameters were 1.32-1.36 mm
B: Table of Varied Parameters
ID No Max Forcesecuring
(N)
Min Dia. during
crimp (mm)
Result
1 155    1.30 visual pass, no leak
2 155    1.2
3 visual pass, no leak
3 155    1.22 visual pass, no leak
4 17
5    1.20  visual pass, no leak
5 175    1.27 visual pass, no leak
Distal: pre-crimp Middle: pre-crimp Proximal: pre-crimp Crimped
6. Testing procedure
A. Acceptance Criteria
⏹All the samples must  sustain the pressure of ≧ 350mmHg after at least 90 days
⏹No strut fracture of the scaffold ring after at least 90 days
⏹No discrete pieces broken off struts after at least 90 days
⏹Marker  holes still round or usable after at least 90 days
B.Scaffold Deployment Procedure for Radial Strength Testing
Step 1          Fill the water bath with water. Place a test tube rack in the water bath. Place a test tube containing ~10mL HPLC grade water in the test tube rack. Ensure the water level inside the test tube is below the
water level in the water bath.
Step 2        Turn on water bath. Allow the water to equilibrate to 37°C ± 1°C.
Step 3  After removing the catheter from the coil, visually inspect the catheter to make sure there are no kinks, cuts or other damage is seen. (This may be done by sliding the pads of the thumb and index finger along
the catheter from the sidearm to the distal end).
Step 4 Hold the catheter and carefully remove the sheath off the scaffold.
Step 5 Do not remove the stylet during scaffold deployment.
Step 6 Remove the air from the catheter using the indeflator by pulling vacuum twice.
Step 7 Load the scaffold assembly in the test tube and securing the assembly using adhesive tape onto the water bath for balloon inflation.
Step 8  Ensure the scaffold is fully submerged in the test tube for 2-5 minutes.
Step 9 Using the indeflator, slowly inflate the scaffold delivery system in the water in 2ATM increments approximately every 5 seconds to the required scaffold deployment pressure as listed below or as listed on
the product package label using the indeflator.
System Diameter (mm)                  3.0    3.5
Nominal Deployment Pressure (atm)  7    6
Step 10      Once nominal pressure is reached, keep the balloon pressurized for approximately 30 seconds and then deflate by pulling vacuum and locking the indeflator.
Step 11 Gently remove the scaffold assembly from the water bath.
Step 12 Gently place the scaffold onto the sheets of low lint wipes along with the stylet.
Step 13 Dry the scaffold between folds of low lint wipes and transfer into a labeled 20 mL scintillation vial.
Note: Make sure the scaffold is dry before transferring into a scintillation glass vial.  During the drying
procedure carefully transfer the scaffold to the respective vial as it gets static when drying.

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