An Innovative Stereolithography 3D Tubular Method for Ultrathin Polymeric Stent Manufacture: The Effect of Process Parameters.

In the last decades, researchers have been developing bioresorbable stents (BRS) to overcome the long-term complications of drug-eluting stents (DES). However, BRS technology still presents challenging limitations in terms of manufacturing, materials, or mechanical properties. At this juncture, companies have developed ultrathin DES that may further improve the efficacy and safety profile of traditional DES by reducing the risk of target-lesion and target-vessel failures until BRS are developed. Nonetheless, the metallic platform of ultrathin DES still presents problems related to their cellular response. The use of polymers as a permanent platform in DES has not previously been studied due to the limitations of current manufacturing technologies. In this work, an innovative manufacturing method for polymeric stent production using tubular stereolithography (SLA) technology is proposed both for BRS and for ultrathin polymeric DES. The effects of manufacturing process parameters were studied by modelling the outcomes (stent thickness and strut width) with the key manufacturing variables (exposure, resin volume, and number of layers). Two different laser setups were used to compare the results. Microscopy results proved the merit of this novel tubular SLA process, which was able to obtain stents with 70 µm strut width and thickness in barely 4 min using only 0.2 mL of resin. Differential Scanning Calorimetry (DSC) results showed the stability of the manufacturing method. The results obtained with this innovative technology are promising and overcome the limitations of other previously used and available technologies.

Continuous Based Direct Ink Write for Tubular Cardiovascular Medical Devices.

Bioresorbable cardiovascular applications are increasing in demand as fixed medical devices cause episodes of late restenosis. The autologous treatment is, so far, the gold standard for vascular grafts due to the similarities to the replaced tissue. Thus, the possibility of customizing each application to its end user is ideal for treating pathologies within a dynamic system that receives constant stimuli, such as the cardiovascular system. Direct Ink Writing (DIW) is increasingly utilized for biomedical purposes because it can create composite bioinks by combining polymers and materials from other domains to create DIW-printable materials that provide characteristics of interest, such as anticoagulation, mechanical resistance, or radiopacity. In addition, bioinks can be tailored to encounter the optimal rheological properties for the DIW purpose. This review delves into a novel emerging field of cardiovascular medical applications, where this technology is applied in the tubular 3D printing approach. Cardiovascular stents and vascular grafts manufactured with this new technology are reviewed. The advantages and limitations of blending inks with cells, composite materials, or drugs are highlighted. Furthermore, the printing parameters and the different possibilities of designing these medical applications have been explored.

Optimization of photocrosslinkable resin components and 3D printing process parameters.

The role of 3D printing in the biomedical field is growing. In this context, photocrosslink-based 3D printing procedures for resorbable polymers stand out. Despite much work, more studies are needed on photocuring stereochemistry, new resin additives, new polymers and resin components. As part of these studies it is vital to present the logic used to optimize the amount of each resin constituent and how that effects printing process parameters. The present manuscript aims to analyze the effects of poly(propylene fumarate) (PPF) resin components and their effect on 3D printing process parameters. Diethyl fumarate (DEF), bisacylphosphine oxide (BAPO), Irgacure 784, 2-hydroxy-4-methoxybenzophenone (HMB) and, for the first time, in biomedical 3D printing, ethyl acetate (EA), were the resin components under investigation in this study. Regarding printing process parameters, Exposure Time, Voxel Depth, and Overcuring Depth were the parameters studied. Taguchi Design of Experiments was used to search for the effect of varying these resin constituent concentrations and 3D printing parameters on the curing behavior of 3D printable PPF resins. Our results indicate that resins with higher polymer cross-link density, especially those with a higher content of PPF, are able to be printed at higher voxel depth and with greater success (i.e., high yield). High voxel depth, as long as it does not sacrifice required resolution, is desirable as it speeds printing. Nevertheless, the overall process is governed by the correct setup of the voxel depth in relation to overcuring depth. In regards to resin biocompatibility, it was observed that EA is more effective than DEF, the material we had previously relied on. Our preliminary in vitro cytotoxicity tests indicate that the use of EA does not reduce scaffold biocompatibility as measured by standard cytotoxicity testing (i.e., ISO 10993-5). We demonstrate a workpath for resin constituent concentration optimization through thin film tests and photocrosslinkable process optimization. STATEMENT OF SIGNIFICANCE: We report here the results of a study of photo-crosslinkable polymer resin component optimization for the 3D printing of resorbable poly(propylene fumarate) (PPF) scaffolds. Resin additives are initially optimized for PPF thin film printing. Once those parameters have been optimized the 3D printing process parameters for PPF objects with complex, porous shapes can be optimized. The design of experiments to optimize both polymer thin films and complex porous resorbable polymer scaffolds is important as a guess and check, or in some cases a systematic method, are very likely to be too time consuming to accomplish. Previously unstudied resin components and process parameters are reported.

Photopolymerizable Resins for 3D-Printing Solid-Cured Tissue Engineered Implants.

With the advent of inexpensive and highly accurate 3D printing devices, a tremendous flurry of research activity has been unleashed into new resorbable, polymeric materials that can be printed using three approaches: hydrogels for bioprinting and bioplotting, sintered polymer powders, and solid cured (photocrosslinked) resins. Additionally, there is a race to understand the role of extracellular matrix components and cell signalling molecules and to fashion ways to incorporate these materials into resorbable implants. These chimeric materials along with microfluidic devices to study organs or create labs on chips, are all receiving intense attention despite the limited number of polymer systems that can accommodate the biofabrication processes necessary to render these constructs. Perhaps most telling is the limited number of photo-crosslinkable, resorbable polymers and fabrication additives (e.g., photoinitiators, solvents, dyes, dispersants, emulsifiers, or bioactive molecules such as micro-RNAs, peptides, proteins, exosomes, micelles, or ceramic crystals) available to create resins that have been validated as biocompatible. Advances are needed to manipulate 4D properties of 3D printed scaffolds such as pre-implantation cell culture, mechanical properties, resorption kinetics, drug delivery, scaffold surface functionalization, cell attachment, cell proliferation, cell maturation, or tissue remodelling; all of which are necessary for regenerative medicine applications along with expanding the small set of materials in clinical use. This manuscript presents a review of the foundation of the most common photopolymerizable resins for solidcured scaffolds and medical devices, namely, polyethylene glycol (PEG), poly(D, L-lactide) (PDLLA), poly-ε-caprolactone (PCL), and poly(propylene fumarate) (PPF), along with methodological advances for 3D Printing tissue engineered implants (e.g., via stereolithography [SLA], continuous Digital Light Processing [cDLP], and Liquid Crystal Display [LCD]).

Screening of Additive Manufactured Scaffolds Designs for Triple Negative Breast Cancer 3D Cell Culture and Stem-Like Expansion.

Breast cancer stem cells (BCSCs) are tumor-initiating cells responsible for metastasis and tumor reappearance, but their research is limited by the impossibility to cultivate them in a monolayer culture. Scaffolds are three-dimensional (3D) cell culture systems which avoid problems related with culturing BCSC. However, a standardized scaffold for enhancing a BCSC population is still an open issue. The main aim of this study is to establish a suitable poly (lactic acid) (PLA) scaffold which will produce BCSC enrichment, thus allowing them to be studied. Different 3D printing parameters were analyzed using Taguchi experimental design methods. Several PLA scaffold architectures were manufactured using a Fused Filament Fabrication (FFF) 3D printer. They were then evaluated by cell proliferation assay and the configurations with the highest growth rates were subjected to BCSC quantification by ALDH activity. The design SS1 (0.2 mm layer height, 70% infill density, Zigzag infill pattern, 45° infill direction, and 100% flow) obtained the highest proliferation rate and was capable of enhancing a ALDH+ cell population compared to 2D cell culture. In conclusion, the data obtained endorse the PLA porous scaffold as useful for culturing breast cancer cells in a microenvironment similar to in vivo and increasing the numbers of BCSCs.

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

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.

Design of a Scaffold Parameter Selection System with Additive Manufacturing for a Biomedical Cell Culture.

Open-source 3D printers mean objects can be quickly and efficiently produced. However, design and fabrication parameters need to be optimized to set up the correct printing procedure; a procedure in which the characteristics of the printing materials selected for use can also influence the process. This work focuses on optimizing the printing process of the open-source 3D extruder machine RepRap, which is used to manufacture poly(ε-caprolactone) (PCL) scaffolds for cell culture applications. PCL is a biocompatible polymer that is free of toxic dye and has been used to fabricate scaffolds, i.e., solid structures suitable for 3D cancer cell cultures. Scaffold cell culture has been described as enhancing cancer stem cell (CSC) populations related to tumor chemoresistance and/or their recurrence after chemotherapy. A RepRap BCN3D+ printer and 3 mm PCL wire were used to fabricate circular scaffolds. Design and fabrication parameters were first determined with SolidWorks and Slic3r software and subsequently optimized following a novel sequential flowchart. In the flowchart described here, the parameters were gradually optimized step by step, by taking several measurable variables of the resulting scaffolds into consideration to guarantee high-quality printing. Three deposition angles (45°, 60° and 90°) were fabricated and tested. MCF-7 breast carcinoma cells and NIH/3T3 murine fibroblasts were used to assess scaffold adequacy for 3D cell cultures. The 60° scaffolds were found to be suitable for the purpose. Therefore, PCL scaffolds fabricated via the flowchart optimization with a RepRap 3D printer could be used for 3D cell cultures and may boost CSCs to study new therapeutic treatments for this malignant population. Moreover, the flowchart defined here could represent a standard procedure for non-engineers (i.e., mainly physicians) when manufacturing new culture systems is required.

A Procedure for Determining Tire-Road Friction Characteristics Using a Modification of the Magic Formula Based on Experimental Results.

Knowledge of tire-road friction characteristics is essential for the proper performance of most relevant vehicle active safety systems. Therefore, its determination is necessary to improve the effectiveness of these systems and to avoid or reduce the consequences of traffic accidents. For this reason, there is a great deal of literature concerning methods and devices for measuring and modeling tire-road friction. Most of these methods have focused on determining the road friction resistance, taking only road composition and making measurements in wet conditions into account. However, friction forces are also dependent on the tire type, since the contact is established between the tire and the road in real driving conditions. Thus, the type and characteristics of the tire have to be considered in the study of the interaction between the vehicle and the road. The aim of this work is to unify the study of the friction coefficient, taking into consideration the two existing bodies involved in the contact, i.e., the tire and road and the main factors that influence the forces in the contact. To this end, a modification of the Pacejka Magic Formula is proposed to include the effects of the main parameters that influence the contact, such as road composition and its state, tire type, vehicle speed, and slip between the tire and the road. To do so, real tests have been conducted on several roads and with different operating conditions. As a result, a more accurate tire-road friction model has been obtained.