Stent’s Manufacturing Field: Past, Present, and Future Prospects

From the introduction of stents, nobody was able to predict the advances that will occur in stent technology over the upcoming decades. Since their appearances, it became evident that this device had significant limitations, such as vessel occlusion and/or restenosis. Despite that, this medical device is the best clinical solution for cardiovascular vessel occlusions. Stents require a deep analysis, in terms of thrombogenicity, manufacturing process, geometrical aspects, and mechanical performance, among many other characteristics. The surface quality obtained in their manufacture process is crucial to blood compatibility, prevents the activation process of thrombosis, and improves the healing efficiency. The forecast stent market makes necessary continuous studies on this field, which help to solve the medical and engineering problems of this device, which are in constant development. Stents have been the center of many research lines over the last decades. The present chapter aims to summarize the state of the art of this medical device in the last years in the fields of design, manufacturing, and materials

Modelling laser milling of microcavities for the manufacturing of DES with ensembles

A set of designed experiments, involving the use of a pulsed Nd:YAG laser system milling 316L Stainless Steel, serve to study the laser-milling process of microcavities in the manufacture of drug-eluting stents (DES). Diameter, depth, and volume error are considered to be optimized as functions of the process parameters, which include laser intensity, pulse frequency, and scanning speed. Two different DES shapes are studied that combine semispheres and cylinders. Process inputs and outputs are defined by considering the process parameters that can be changed under industrial conditions and the industrial requirements of this manufacturing process. In total, 162 different conditions are tested in a process that is modeled with the following state-of-the-art data-mining regression techniques: Support Vector Regression, Ensembles, Artificial Neural Networks, Linear Regression, and Nearest Neighbor Regression. Ensemble regression emerged as the most suitable technique for studying this industrial problem. Specifically, Iterated Bagging ensembles with unpruned model trees outperformed the other methods in the tests. This method can predict the geometrical dimensions of the machined microcavities with relative errors related to the main average value in the range of 3 to 23%, which are considered very accurate predictions, in view of the characteristics of this innovative industrial task.This work was partially funded through Grants fromthe IREBID Project (FP7-PEOPLE-2009-IRSES- 247476) of the European Commission and Projects TIN2011- 24046 and TECNIPLAD (DPI2009-09852) of the Spanish Ministry of Economy and Competitivenes

Three-dimensional printed bone scaffolds:The role of nano/micro-hydroxyapatite particles on the adhesion and differentiation of human mesenchymal stem cells

Bone tissue engineering is strongly dependent on the use of three-dimensional scaffolds that can act as templates to accommodate cells and support tissue ingrowth. Despite its wide application in tissue engineering research, polycaprolactone presents a very limited ability to induce adhesion, proliferation and osteogenic cell differentiation. To overcome some of these limitations, different calcium phosphates, such as hydroxyapatite and tricalcium phosphate, have been employed with relative success. This work investigates the influence of nano-hydroxyapatite and micro-hydroxyapatite (nHA and mHA, respectively) particles on the in vitro biomechanical performance of polycaprolactone/hydroxyapatite scaffolds. Morphological analysis performed with scanning electron microscopy allowed us to confirm the production of polycaprolactone/hydroxyapatite constructs with square interconnected pores of approximately 350 µm and to assess the distribution of hydroxyapatite particles within the polymer matrix. Compression mechanical tests showed an increase in polycaprolactone compressive modulus ( E) from 105.5 ± 11.2 to 138.8 ± 12.9 MPa (PCL_nHA) and 217.2 ± 21.8 MPa (PCL_mHA). In comparison to PCL_mHA scaffolds, the addition of nano-hydroxyapatite enhanced the adhesion and viability of human mesenchymal stem cells as confirmed by Alamar Blue assay. In addition, after 14 days of incubation, PCL_nHA scaffolds showed higher levels of alkaline phosphatase activity compared to polycaprolactone or PCL_mHA structures. </jats:p

Quantum atom-light interfaces in the gaussian description for spin-1 systems

We extend the covariance-matrix description of atom--light quantum interfaces, originally developed for real and effective spin-1/2 atoms, to include "spin alignment" degrees of freedom. This allows accurate modeling of optically-probed spin-1 ensembles in arbitrary magnetic fields. We also include technical noise terms that are very common in experimental situations. These include magnetic field noise, variable atom number and the effect of magnetic field inhomogeneities. We demonstrate the validity of our extended model by comparing numerical simulations to a free--induction decay (FID) measurement of polarized $^{87}$Rb atoms in the $f = 1$ ground state. We qualitatively and quantitatively reproduce experimental results with all free parameters of the simulations fixed. The model can be easily extended to larger spin systems, and adapted to more complicated experimental situations.Comment: 25 pages, 4 figure

Solvent-cast direct-writing and electrospinning as a dual fabrication strategy for drug-eluting polymeric bioresorbable stents

Bioresorbable stents (BRS) are conceived to retain sufficient radial strength after implantation while releasing an antiproliferative drug in order to prevent vessel restenosis until complete resorption. Ongoing research trends involve the use of innovative manufacturing techniques to achieve thinner struts combined with optimized local drug delivery. This work presents a combination of solvent-cast direct-writing (SC-DW) and electrospinning (ES) using poly-l-lactic acid (PLLA) and poly(l-lactic-co-¿-caprolactone) (PLCL) as a new approach to generate everolimus-eluting BRS for cardiovascular applications. A Design of Experiment (DoE) was conducted to determine the optimal parameters to obtain a homogeneous coating with high specific surface. Manufactured stents were characterized by means of mechanical tests and scanning electron microscopy (SEM), with everolimus release in accelerated conditions quantified through High Performance Liquid Chromatography (HPLC). Drug loading was achieved either encapsulated in the struts of the stent or in an electrospun PLCL membrane covering the stent. In the former case, everolimus release was found to be insufficient, less than 3% of total drug loading after 8 weeks. In the latter, everolimus release considerably increased with respect to drug-loaded 3D-printed stents, with over 50% release in the first 6 hours of the test. In conclusion, everolimus release from PLCL-coated 3D-printed stents would match the dose and timeframe required for in vivo applications, while providing thinner struts than SC-DW drug-loaded stents.Peer ReviewedPostprint (published version

Fatty Acid Synthase Inhibitor G28 Shows Anticancer Activity in EGFR Tyrosine Kinase Inhibitor Resistant Lung Adenocarcinoma Models

Epidermal growth factor receptor (EGFR) tyrosine kinases inhibitors (TKIs) are effectivetherapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor an EGFR activatingmutation. However, this treatment is not curative due to primary and secondary resistance suchas T790M mutation in exon 20. Recently, activation of transducer and activator of transcription 3(STAT3) in NSCLC appeared as an alternative resistance mechanism allowing cancer cells to elude theEGFR signaling. Overexpression of fatty acid synthase (FASN), a multifunctional enzyme essentialfor endogenous lipogenesis, has been related to resistance and the regulation of the EGFR/Jak2/STATsignaling pathways. Using EGFR mutated (EGFRm) NSCLC sensitive and EGFR TKIs' resistantmodels (Gefitinib Resistant, GR) we studied the role of the natural polyphenolic anti-FASN compound(−)-epigallocatechin-3-gallate (EGCG), and its derivative G28 to overcome EGFR TKIs' resistance.We show that G28's cytotoxicity is independent of TKIs' resistance mechanisms displaying synergisticeffects in combination with gefitinib and osimertinib in the resistant T790M negative (T790M−)model and showing a reduction of activated EGFR and STAT3 in T790M positive (T790M+) models.Our results provide the bases for further investigation of G28 in combination with TKIs to overcomethe EGFR TKI resistance in NSCLC

Meta-heuristic improvements applied for steel sheet incremental cold shaping

In previous studies, a wrapper feature selection method for decision support in steel sheet incremental cold shaping process (SSICS) was proposed. The problem included both regression and classification, while the learned models were neural networks and support vector machines, respectively. SSICS is the type of problem for which the number of features is similar to the number of instances in the data set, this represents many of real world decision support problems found in the industry. This study focuses on several questions and improvements that were left open, suggesting proposals for each of them. More specifically, this study evaluates the relevance of the different cross validation methods in the learned models, but also proposes several improvements such as allowing the number of chosen features as well as some of the parameters of the neural networks to evolve, accordingly. Well-known data sets have been use in this experimentation and an in-depth analysis of the experiment results is included. 5 × 2 CV has been found the more interesting cross validation method for this kind of problems. In addition, the adaptation of the number of features and, consequently, the model parameters really improves the performance of the approach. The different enhancements have been applied to the real world problem, an several conclusions have been drawn from the results obtained

Electrospinning PCL Scaffolds Manufacture for Three-Dimensional Breast Cancer Cell Culture

In vitro cell culture is traditionally performed within two-dimensional (2D) environments, providing a quick and cheap way to study cell properties in a laboratory. However, 2D systems differ from the in vivo environment and may not mimic the physiological cell behavior realistically. For instance, 2D culture models are thought to induce cancer stem cells (CSCs) differentiation, a rare cancer cell subpopulation responsible for tumor initiation and relapse. This fact hinders the development of therapeutic strategies for tumors with a high relapse percentage, such as triple negative breast cancer (TNBC). Thus, three-dimensional (3D) scaffolds have emerged as an attractive alternative to monolayer culture, simulating the extracellular matrix structure and maintaining the differentiation state of cells. In this work, scaffolds were fabricated through electrospinning different poly(ε-caprolactone)-acetone solutions. Poly(ε-caprolactone) (PCL) meshes were seeded with triple negative breast cancer (TNBC) cells and 15% PCL scaffolds displayed significantly (p &lt; 0.05) higher cell proliferation and elongation than the other culture systems. Moreover, cells cultured on PCL scaffolds exhibited higher mammosphere forming capacity and aldehyde dehydrogenase activity than 2D-cultured cells, indicating a breast CSCs enrichment. These results prove the powerful capability of electrospinning technology in terms of poly(ε-caprolactone) nanofibers fabrication. In addition, this study has demonstrated that electrospun 15% PCL scaffolds are suitable tools to culture breast cancer cells in a more physiological way and to expand the niche of breast CSCs. In conclusion, three-dimensional cell culture using PCL scaffolds could be useful to study cancer stem cell behavior and may also trigger the development of new specific targets against such malignant subpopulation