Effects of shape and structure of a new 3D-printed personalized bioresorbable tracheal stent on fit and biocompatibility in a rabbit model.

To date, several types of airway stents are available to treat central airway obstructions. However, the ideal stent that can overcome anatomical, mechanical and microbiological issues is still awaited. In addition, therapeutic effect and self-elimination of these stents are desirable properties, which pose an additional challenge for development and manufacturing. We aimed to create a prototype bioresorbable tracheal stent with acceptable clinical tolerance, fit and biocompatibility, that could be tested in a rabbit model and in the future be further optimized to enable drug-elution and ensure local therapeutic effect. Twenty-one New Zealand White Rabbits received five different types of bioresorbable tracheal stents, 3D-printed from poly(D,L-lactide-co-ε-caprolactone) metacrylates. Various configurations were tested for their functionality and improved until the best performing prototype could undergo detailed in vivo assessment, regarding clinical tolerance, migration and biocompatibility. Previously tested types of 3D printed stents in our preliminary study required improvement due to several problems, mainly related to breakage, unreliable stability and/or migration within the trachea. Abandoned or refined pre-prototypes were not analyzed in a comparative way. The final best performing prototype stent (GSP2 (Group Stent Prototype 2), n = 8) allowed a transoral application mode and showed good clinical tolerance, minimal migration and acceptable biocompatibility. The good performance of stent type GSP2 was attributed to the helix-shaped surface structure, which was therefore regarded as a key-feature. This prototype stent offers the possibility for further research in a large animal model to confirm the promising data and assess other properties such as bioresorption.

Digital Light 3D Printed Bioresorbable and NIR-Responsive Devices with Photothermal and Shape-Memory Functions.

Digital light processing (DLP) 3D printing is a promising technique for the rapid manufacturing of customized medical devices with high precision. To be successfully translated to a clinical setting, challenges in the development of suitable photopolymerizable materials have yet to be overcome. Besides biocompatibility, it is often desirable for the printed devices to be biodegradable, elastic, and with a therapeutic function. Here, a multifunctional DLP printed material system based on the composite of gold nanorods and polyester copolymer is reported. The material demonstrates robust near-infrared (NIR) responsiveness, allowing rapid and stable photothermal effect leading to the time-dependent cell death. NIR light-triggerable shape transformation is demonstrated, resulting in a facilitated insertion and expansion of DLP printed stent ex vivo. The proposed strategy opens a promising avenue for the design of multifunctional therapeutic devices based on nanoparticle-polymer composites.

3D printed elastomers with Sylgard-184-like mechanical properties and tuneable degradability.

The 3D printing of biodegradable elastomers with high mechanical strength is of great interest for personalized medicine, but rather challenging. In this study, we propose a dual-polymer resin formulation for digital light processing of biodegradable elastomers with tailorable mechanical properties comparable to those of Sylgard-184.

Light-Based Printing of Leachable Salt Molds for Facile Shaping of Complex Structures.

3D printing is a powerful manufacturing technology for shaping materials into complex structures. While the palette of printable materials continues to expand, the rheological and chemical requisites for printing are not always easy to fulfill. Here, a universal manufacturing platform is reported for shaping materials into intricate geometries without the need for their printability, but instead using light-based printed salt structures as leachable molds. The salt structures are printed using photocurable resins loaded with NaCl particles. The printing, debinding, and sintering steps involved in the process are systematically investigated to identify ink formulations enabling the preparation of crack-free salt templates. The experiments reveal that the formation of a load-bearing network of salt particles is essential to prevent cracking of the mold during the process. By infiltrating the sintered salt molds and leaching the template in water, complex-shaped architectures are created from diverse compositions such as biomedical silicone, chocolate, light metals, degradable elastomers, and fiber composites, thus demonstrating the universal, cost-effective, and sustainable nature of this new manufacturing platform.

Physical methods for enhancing drug absorption from the gastrointestinal tract.

Overcoming the gastrointestinal (GI) barriers is a formidable challenge in the oral delivery of active macromolecules such as peptide- and protein- based drugs. In the past four decades, a plethora of formulation strategies ranging from permeation enhancers, nanosized carriers, and chemical modifications of the drug's structure has been investigated to increase the oral absorption of these macromolecular compounds. However, only limited successes have been achieved so far, with the bioavailability of marketed oral peptide drugs remaining generally very low. Recently, a few approaches that are based on physical interactions, such as magnetic, acoustic, and mechanical forces, have been explored in order to control and improve the drug permeability across the GI mucosa. Although in the early stages, some of these methods have shown great potential both in terms of improved bioavailability and spatiotemporal delivery of drugs. Here, we offer a concise, yet critical overview of these rather unconventional technologies with a particular focus on their potential and possible challenges for further clinical translation.

Digital light 3D printing of customized bioresorbable airway stents with elastomeric properties.

Central airway obstruction is a life-threatening disorder causing a high physical and psychological burden to patients. Standard-of-care airway stents are silicone tubes, which provide immediate relief but are prone to migration. Thus, they require additional surgeries to be removed, which may cause tissue damage. Customized bioresorbable airway stents produced by 3D printing would be highly needed in the management of this disorder. However, biocompatible and biodegradable materials for 3D printing of elastic medical implants are still lacking. Here, we report dual-polymer photoinks for digital light 3D printing of customized and bioresorbable airway stents. These stents exhibit tunable elastomeric properties with suitable biodegradability. In vivo study in healthy rabbits confirmed biocompatibility and showed that the stents stayed in place for 7 weeks after which they became radiographically invisible. This work opens promising perspectives for the rapid manufacturing of the customized medical devices for which high precision, elasticity, and degradability are sought.

Arterial stiffness as a predictor of recovery of left ventricular systolic function after acute myocardial infarction treated with primary percutaneous coronary intervention.

Left ventricular ejection fraction (LVEF) and pulse wave velocity (PWV) are acknowledged as independent risk factors in different high-risk populations. We investigated the effects of arterial stiffness on LV function at 3 and 6 months after acute myocardial infarction. Changes in LVEF were evaluated in 136 consecutive patients who were diagnosed with ST-segment elevation coronary syndrome and treated with primary percutaneous coronary intervention. Doppler guided by 2D ultrasound was used to measure carotid-femoral PWV. According to tertiles of arterial stiffness, a significant correlation between higher PWV and worse recovery in LVEF was found (3 months EF change: 9.9 ± 5.0% vs 5.9 ± 3.4 vs 3.8 ± 1.6; p < 0.001 and 6 months EF change: 18.5 ± 7.0% vs 11.5 ± 5.2 vs 7.3 ± 3.0; p = 0.002). In the multivariate analysis PWV showed the ability to predict the outcome in terms of EF recovery at 3 and 6 months also after any correction for age and other variables (ß = -0.566, p < 0.001). Arterial stiffening may result in a less effective recovery of LV function after acute myocardial infarction.