Implanted cardiovascular polymers: Natural, synthetic and bio-inspired

Laser-based direct writing of materials has undergone significant development in recent years. The ability to modify a variety of materials at small length scales and using short production times provides laser direct writing with unique capabilities for fabrication of medical devices. In many laser-based rapid prototyping methods, microscale and submicroscale structuring of materials is controlled by computer-generated models. Various laser-based direct write methods, including selective laser sintering/melting, laser machining, matrix-assisted pulsed-laser evaporation direct write, stereolithography and two-photon polymerization, are described. Their use in fabrication of microstructured and nanostructured medical devices is discussed. Laser direct writing may be used for processing a wide variety of advanced medical devices, including patient-specific prostheses, drug delivery devices, biosensors, stents and tissue-engineering scaffolds.

/pdf/laser-direct-writing-of-micro-and-nano-scale-medical-devices-30b7ffl22h.pdf

Laser direct writing of micro- and nano-scale medical devices

Biodegradable stents for coronary artery disease treatment: Recent advances and future perspectives.

Background The development of endoluminal stents from polymeric materials requires an understanding of the basic mechanical properties of the polymer and the effects of manufacturing and sterilization on those properties. Methods Pure poly(L-lactide) (PLLA) and PLLA containing varying amounts of triethylcitrate (TEC) as a plasticizer (5-10-15%) were studied. The specimens were solution-cast and CO2 laser-cut. Specimen dimensions were adapted to the strut size of polymeric vascular stents. The properties of the PLLA micro-specimens were assessed before and after sterilization (EtO cold gas, H2O2-plasma, beta- and gamma-irradiation). Tensile tests, and creep and recovery tests were carried out at 37 degrees C. Additionally the thermal and thermo-mechanical characteristics were investigated using dynamic-mechanical analysis (DMA) and differential scanning calorimetry (DSC). Results The results showed the dramatic influence of the plasticizer content and sterilization procedure on the mechanical properties of the material. Laser cutting had a lesser effect. Hence the effects of processing and sterilization must not be overlooked in the material selection and design phases of the development process leading to clinical use. Altogether, the results of these studies provide a clearer understanding of the complex interaction between the laser machining process and terminal sterilization on the primary mechanical properties of PLLA and PLLA plasticized with TEC.

Mechanical Properties of Laser Cut Poly(L-Lactide) Micro-Specimens: Implications for Stent Design, Manufacture, and Sterilization

Biodegradable stents (BRS) offer enormous potential but first they must meet five specific requirements: (i) their manufacturing process must be precise; (ii) degradation should have minimal toxicity; (iii) the rate of degradation should match the recovery rate of vascular tissue; (iv) ideally, they should induce rapid endothelialization to restore the functions of vascular tissue, but at the same time reduce the risk of restenosis; and (v) their mechanical behavior should comply with medical requirements, namely, the flexibility required to facilitate placement but also sufficient radial rigidity to support the vessel. Although the first three requirements have been comprehensively studied, the last two have been overlooked. One possible way of addressing these issues would be to fabricate composite stents using materials that have different mechanical, biological, or medical properties, for instance, Polylactide Acid (PLA) or Polycaprolactone (PCL). However, fashioning such stents using the traditional stent manufacturing process known as laser cutting would be impossible. Our work, therefore, aims to produce PCL/PLA composite stents using a novel 3D tubular printer based on Fused Deposition Modelling (FDM). The cell geometry (shape and area) and the materials (PCL and PLA) of the stents were analyzed and correlated with 3T3 cell proliferation, degradation rates, dynamic mechanical and radial expansion tests to determine the best parameters for a stent that will satisfy the five strict BRS requirements. Results proved that the 3D-printing process was highly suitable for producing composite stents (approximately 85–95% accuracy). Both PCL and PLA demonstrated their biocompatibility with PCL stents presenting an average cell proliferation of 12.46% and PLA 8.28% after only 3 days. Furthermore, the PCL/PLA composite stents demonstrated their potential in degradation, dynamic mechanical and expansion tests. Moreover, and regardless of the order of the layers, the composite stents showed (virtually) medium levels of degradation rates and mechanical modulus. Radially, they exhibited the virtues of PCL in the expansion step (elasticity) and those of PLA in the recoil step (rigidity). Results have clearly demonstrated that composite PCL/PLA stents are a highly promising solution to fulfilling the rigorous BRS requirements.

https://www.mdpi.com/1996-1944/11/9/1679/pdf

3D-Printed PCL/PLA Composite Stents: Towards a New Solution to Cardiovascular Problems

Stents made of biodegradable polymers have first been suggested to treat cardiovascular diseases more than ten years ago. Despite the enormous potential of local drug delivery there is no biodegradable coronary stent available today. Some of the problems concern the insufficient mechanical properties of the stent designs. Therefore a design strategy was developed to improve the mechanical properties of balloon-expandable polymer stents. Starting with compiling the possible geometric strut forms we proceeded to design strut features exhibiting an improved deformation behaviour. The addition of functional structures to improve certain stent characteristics led to stent designs, whose mechanical properties, recoil and collaps behaviour, were determined by 3D Finite Element Analysis. Finally, a mechanical in vitro testing of these stent prototypes was conducted.

[Design strategy for balloon-expandable stents made of biodegradable polymers using finite element analysis].

Polimeric stents: aspects of structural mechanics in design and development

. : Within thc last ycars a lot of scientists v'niMivd in thc dcvclopment of various forms of biorcsoiluhlc Mcnts. Thcrc arc still many unsolved problems Loikvinmg o.g. mcchanical strength and the sccure imphmtation, so that thcrc is no bioresorbable stent commerunl ly variable today. ( Hu vvorks on balloon expandable, laser cuttcd stents toi coronai v äs well äs for peripheral and urological appli-

Biodegradable polymeric stents: the influence of plasticizer content on the mechanical properties

Introduction: Instead of vascular metallic stents with their permanent implant nature biodegradable stents can be applied. The aim of the study was to investigate the influence of Acetylsalicylic acid (ASA) versus ASA/Clopidogrel (CLOP) on acute/subacute thrombotic occlusion of a Poly-L-Lactid Acid (PLLA) stent after implantation in a porcine iliac model of stenosis. Materials and methods: A polytetrafluoroethylene (PTFE) aortobi-iliac graft (12/6 mm) was implanted in pigs (body weight bw: 37.4 ± 1.9) with creating of an iliac anastomotic stenosis. PLLA-stents (n=11) were placed across the distal anastomosis unilaterally (right: 6, left: 5) und balloon-dilated to 6 mm. Beginning 1 day before operation and continuing until the end of the study, the pigs received ASA 100mg orally alone (n=5) or in combination with CLOP 75mg orally (n=6). Intravenous heparin (50 IU/kg bw hourly) was administered as a continous infusion during the procedure. Doppler ultrasound (4MHz) was performed at the femoral arteries. After a follow-up aortoiliac CT-scan at 1 week, the segments containing the stents were surgically explanted and processed for histology (HE), and the animals were sacrified. Results: All PLLA-stents were sucessfully delivered at the distal anastomotic region and showed a complete stent-arterial wall contact after deployment on a macroscopically view. Stenting was successful in eliminating the anastomotic stenosis, proved by femoral doppler measurement, i.e. the poststenotic flow was abolished. One animal died 3 days after operation due to distortion of the right colon resulting in gangrene. At 1 week, all PLLA-stents using ASA alone (n=4) were shown to be occluded, whereas all PLLA-stents under the combination of ASA and CLOP (n=6) and all non-stented anastomotic sites (n=4) were patent. The residual lumen diameter was significant higher at the PLLA-stented (4.54 mm ± 0.16) than at the non-stented (1.89 mm ± 0.33) anastomotic site, p<0.001. The percent lumen stenosis of the PLLA-stented group amounted to 28.48% ± 2.98 compared to 61.01% ± 7.02 (p<0.001) of the the non-stented group, related to the inner diameter of the graft (6.35 mm ± 0.11 and 4.85 mm ± 0.03, respectively). The PLLA-stent associated neointimal restenosis was 5.07% ± 1.76, related to the normal lumen diameter (within the internal elastic lamina) of 4.78 mm ± 0.09. Conclusion: Acute/subacute occlusion of the PLLA-stent was prevented by a combination of ASA and CLOP. No significant stent-induced re-stenosis was observed. A longer follow-up period, however, is mandatory to evaluate chronic thrombosis/re-stenosis and the degradation behaviour.

M. Schlun

Papers

Mechanical Properties of Laser Cut Poly(L-Lactide) Micro-Specimens: Implications for Stent Design, Manufacture, and Sterilization

[Design strategy for balloon-expandable stents made of biodegradable polymers using finite element analysis].

Polimeric stents: aspects of structural mechanics in design and development

Biodegradable polymeric stents: the influence of plasticizer content on the mechanical properties

Biodegradierbarer Poly-L-Lactid-Stent im iliakalen Stenose-Modell am Schwein: Kombination aus ASS und Clopidogrel verhindert Thrombose