Tré R. Welch

A novel biodegradable stent applicable for use in congenital heart disease: bench testing and feasibility results in a rabbit model.

A novel double opposed helical (DH) biodegradable stent was designed and fabricated for CHD applications. The primary objective was to evaluate the feasibility of DH stent delivery and deployment in rabbit external iliac arteries (EIA). Secondary objectives were to assess stent patency, thrombosis and inflammation at 1‐week and 1‐month follow‐up.

The influence of thermal treatment on the mechanical characteristics of a PLLA coiled stent.

We studied the effects of thermal treatment on the expansive characteristics of a coil-within-coil Poly(L-lactic acid) (PLLA) fiber stent developed at our institution to improve its mechanical performance and reproducibility. Following fabrication, furled stents were thermally treated at 62 degrees C for 25 min. The mechanical characteristics were measured compared with those of untreated stents when both were expanded via sequential balloon catheter pressure loading up to 12 atm. Treated stents reached full diameter at 3 atm and maintained that diameter despite further pressure increases. Using measurements of pressure, diameter, and axial length, we calculated the sequential mechanical work required to unfurl the stent. The mechanical work for complete unfurling of treated stents was significantly less than that required for untreated controls. Little axial dimensional change was observed for treated stents. Treated stents exhibited higher stiffness than controls at all pressure levels and also demonstrated higher resistance to external pressure-induced collapse, as measured in a special apparatus developed in our laboratory. Differential scanning calorimetry measurements indicated higher crystallinity values for fibers used in treated stents compared with controls. SEM examination of striations revealed that treated stents underwent less twist than controls following balloon-induced unfurling. The results indicate that, thermal treatment improves the reorientation and realignment of fiber crystalline structure, and favorably influences on the fiber stress-strain behavior and the expansive mechanical characteristics of the PLLA fiber stents.

A novel design biodegradable stent for use in congenital heart disease: Mid-term results in rabbit descending aorta

This study evaluates the feasibility of delivery and deployment of low and medium molecular weight (LMW and MMW, respectively) double‐opposing helical (DH) poly‐l‐lactic acid biodegradable stent (BDS) in rabbit descending aorta (DAO). Secondary objectives were to assess patency and inflammation of stented vessels at 9 months and to investigate safety following intentional embolization of stent fragments in DAO.

Novel bioresorbable stent coating for drug release in congenital heart disease applications

A novel double opposed helical poly-l-lactic acid (PLLA) bioresorbable stent has been designed for use in pediatrics. The aim was to test the PLLA stent biocompatibility. The PLLA stent was immersed into whole pigs blood in a closed loop circuit then fibrin and platelet association was assessed via enzyme-linked immunosorbent assay. D-Dimer was valued at 0.2 ± 0.002 ng/mL and P-selectin 0.43 ± 00.01 ng/mL indicating limited association of fibrin and platelets on the stent. To improve biocompatibility by targeting inflammatory cells, dexamethasone was incorporated on PLLA fibers with two coating methods. Both coatings were poly(l-lactide-co-glycolide) acid (PLGA) but one was made porous with sucrose while the other remained nonporous. There was no change in mechanical properties of the fiber with either coating of PLGA polymer. The total amount of dexamethasone released was then determined for each coating. The cumulative drug release for the porous fiber was significantly higher (∼100%) over 8 weeks than the nonporous fiber (40%). Surface examination of the fiber with scanning electron microscopy showed more surface microfracturing in coatings that contain pores. The biocompatibility of this novel stent was demonstrated. Mechanical properties of the fiber were not altered by coating with PLGA polymer. Anti-inflammatory drug release was optimized using a porous PLGA polymer.

Thermally processed polymeric microparticles for year-long delivery of dexamethasone

Dexamethasone-releasing poly(lactic-co-glycolic acid) (PLGA) microparticles were formulated using a solvent displacement technique with the addition of distillation aiming to increase drug delivery lifetime. Two PLGA copolymer ratios (50:50 and 75:25) were used to determine the influence of lactic acid and glycolic acid ratio on microparticle characteristics. The addition of distillation significantly slows the release of dexamethasone compared to traditional solvent removal via evaporation while still maintaining a therapeutic dosage. Microparticles formulated with PLGA 50:50 controllably release dexamethasone up to one year and 75:25 release up to two years in-vitro. The ratio of lactic acid to glycolic acid plays a significant role in microparticle stability, drug loading efficiency, and thermal properties. In all, this formulation technique offers new prospects for inflammation suppression in pediatric vascular and airway diseases.

Thymosin β4 sustained release from poly(lactide-co-glycolide) microspheres: synthesis and implications for treatment of myocardial ischemia.

A sustained release formulation for the therapeutic peptide thymosin β4 (Tβ4) that can be localized to the heart and reduce the concentration and frequency of dose is being explored as a means to improve its delivery in humans. This review contains concepts involved in the delivery of peptides to the heart and the synthesis of polymer microspheres for the sustained release of peptides, including Tβ4. Initial results of poly(lactic‐co‐glycolic acid) microspheres synthesized with specific tolerances for intramyocardial injection that demonstrate the encapsulation and release of Tβ4 from double‐emulsion microspheres are also presented.

Bench and initial preclinical results of a novel 8 mm diameter double opposed helical biodegradable stent

Metallic endovascular stents are utilized off‐label in congenital heart disease. Biodegradable stents (BDS) offer potential advantages in a growing child. We have previously reported double opposed helical (DH) BDS up to 6 mm diameter (DH‐6). The objectives are to investigate the bench characteristics of larger 8 mm diameter BDS (DH‐8) manufactured with increasing strut thicknesses and the inflammatory profile in a porcine model.

On the capabilities of a multi-modality 3D bioprinter for customized biomedical devices

Currently, there is a major shift in medical device fabrication research towards layer-by-layer additive manufacturing technologies; mainly owing to the relatively quick transition from a solid model (.STL file) to an actual prototype. The current manuscript introduces a Custom Multi-Modality 3D Bioprinter (CMMB) developed in-house, combining the Fused Filament Fabrication (FFF), Photo Polymerization (PP), Viscous Extrusion (VE), and Inkjet (IJ) printing technologies onto a single additive manufacturing platform. Methodologies to address limitation in the ability to customize construct properties layer-by-layer and to incorporate multiple materials in a single construct have been evaluated using open source 3D printing softwares Slic3r and Repetier-Host. Such customization empowers the user to fabricate constructs with tailorable anisotropic properties by combining different print technologies and materials. To this end, procedures which allow the integration of more than one distinct modality of the CMMB during a single print session were developed and evaluated, and are discussed. The current setup of the CMMB provides the capability to fabricate personalized medical devices using patient data from an MRI or a CT scan. Initial experiments and fabricated constructs demonstrate the potential of the CMMB for research in diverse application areas within biomedical engineering.Copyright

Influence of CO2 Blowing Agent on Porous Bioresorbable Stent Structure

Bioresorbable stents with limited functional lifetimes and with drug delivery capabilities are desired. Various methods have been investigated to induce porosity in bioresorbable polymeric stent fibers, thereby to permit increased drug reservoir capacity versus polymer-coated metal stents. We developed microporous surface layers on PLLA fibers to serve as the drug reservoir, but found that impurities, the use of chemicals, and multiple step procedures associated with our, and other published methods limited utility. Thus we investigated theoretically attractive CO2 blowing methods, in which gas under pressure and temperature induces porosity. We report the results of initial studies of CO2-induced porosity in PLLA stent fibers.Copyright

Thermal treatment effects on a PLLA bioresorbable stent

Stent navigation and expansion may injure vascular endothelium, including vulnerable plaque lesions. Balloon expansion and deployment of a stent can lead to injury or the endothelial lining and stretching of the arterial wall [1]. Understanding the traction forces an expanding stent imparts on the vascular wall at the endothelial surface, the underlying plaque lesions and other tissue components during expansion is an important step in improving short term stent-wall mechanics. More importantly, the long term influence of stent-vascular wall mechanical interactions in restenosis remains unknown, and this analysis may shed light on the process.Copyright