Carboxymethyl-Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles for Drug Delivery: Influence of the Coating Thickness on the Particle Properties.

Carboxymethyl-dextran (CMD)-coated iron oxide nanoparticles (IONs) are of great interest in nanomedicine, especially for applications in drug delivery. To develop a magnetically controlled drug delivery system, many factors must be considered, including the composition, surface properties, size and agglomeration, magnetization, cytocompatibility, and drug activity. This study reveals how the CMD coating thickness can influence these particle properties. ION@CMD are synthesized by co-precipitation. A higher quantity of CMD leads to a thicker coating and a reduced superparamagnetic core size with decreasing magnetization. Above 12.5−25.0 g L−1 of CMD, the particles are colloidally stable. All the particles show hydrodynamic diameters < 100 nm and a good cell viability in contact with smooth muscle cells, fulfilling two of the most critical characteristics of drug delivery systems. New insights into the significant impact of agglomeration on the magnetophoretic behavior are shown. Remarkable drug loadings (62%) with the antimicrobial peptide lasioglossin and an excellent efficiency (82.3%) were obtained by covalent coupling with the EDC/NHS (N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) method in comparison with the adsorption method (24% drug loading, 28% efficiency). The systems showed high antimicrobial activity with a minimal inhibitory concentration of 1.13 µM (adsorption) and 1.70 µM (covalent). This system successfully combines an antimicrobial peptide with a magnetically controllable drug carrier.

Deferiprone Stimulates Aged Dermal Fibroblasts via HIF-1α Modulation.

BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α), a transcription factor responsible for tissue homeostasis and regeneration, presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator deferiprone (DFP) at stimulating dermal fibroblasts. OBJECTIVES: The main objective of this study was to quantify the DFP concentrations capable of stimulating dermal fibroblasts in vitro and to correlate the effective DFP concentrations with the ability of DFP to penetrate the epidermis, reach the dermis, and activate HIF-1α in vivo. METHODS: We measured cell proliferation, metabolic activity, HIF-1α expression, and lactate dehydrogenase levels of both young and aged fibroblasts after a 24-hour in vitro preconditioning with DFP. In addition, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% DFP topical formulation to quantify the concentration required to reach the dermis. RESULTS: In vitro administration of iron-chelation therapy (156-312.5 µg/mL DFP ) on aged fibroblasts resulted in activation of various antiaging processes. The concentration required to reach the dermis within 24 hours was 1.5% (0.15 mg/mL), which corresponds well with the effective doses of our laboratory analyses. CONCLUSIONS: The activation of HIF-1α by DFP enhances cell metabolism, proliferation, and survival of fibroblasts while reducing lactate dehydrogenase levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, antiaging. Therefore, the antiaging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.

Biologically Inspired Scaffolds for Heart Valve Tissue Engineering via Melt Electrowriting.

Heart valves are characterized to be highly flexible yet tough, and exhibit complex deformation characteristics such as nonlinearity, anisotropy, and viscoelasticity, which are, at best, only partially recapitulated in scaffolds for heart valve tissue engineering (HVTE). These biomechanical features are dictated by the structural properties and microarchitecture of the major tissue constituents, in particular collagen fibers. In this study, the unique capabilities of melt electrowriting (MEW) are exploited to create functional scaffolds with highly controlled fibrous microarchitectures mimicking the wavy nature of the collagen fibers and their load-dependent recruitment. Scaffolds with precisely-defined serpentine architectures reproduce the J-shaped strain stiffening, anisotropic and viscoelastic behavior of native heart valve leaflets, as demonstrated by quasistatic and dynamic mechanical characterization. They also support the growth of human vascular smooth muscle cells seeded both directly or encapsulated in fibrin, and promote the deposition of valvular extracellular matrix components. Finally, proof-of-principle MEW trileaflet valves display excellent acute hydrodynamic performance under aortic physiological conditions in a custom-made flow loop. The convergence of MEW and a biomimetic design approach enables a new paradigm for the manufacturing of scaffolds with highly controlled microarchitectures, biocompatibility, and stringent nonlinear and anisotropic mechanical properties required for HVTE.

Bacterial reduction and temperature increase of titanium dental implant models treated with a 445 nm diode laser: an in vitro study.

In this in vitro study, the use of a 445 nm diode laser was investigated for the decontamination of titanium dental implants. Different irradiation protocols and the effect of repetitive laser irradiation on temperature increase and decontamination efficacy were evaluated on titanium implant models. An automated setup was developed to realize a scanning procedure for a full surface irradiation to recapitulate a clinical treatment. Three irradiation parameter sets A (continuous wave, power 0.8 W, duty cycle (DC) 100%, and 5 s), B (pulsed mode, DC 50%, power 1.0 W, and 10 s), and C (pulsed mode, DC 10%, power 3.0 W, and 20 s) were used to treat the rods for up to ten consecutive scans. The resulting temperature increase was measured by a thermal imaging camera and the decontamination efficacy of the procedures was evaluated against Escherichia coli and Staphylococcus aureus, and correlated with the applied laser fluence. An implant's temperature increase of 10 °C was set as the limit accepted in literature to avoid thermal damage to the surrounding tissue in vivo. Repeated irradiation of the specimens resulted in a steady increase in temperature. Parameter sets A and B caused a temperature increase of 11.27 ± 0.81 °C and 9.90 ± 0.37 °C after five consecutive laser scans, respectively, while parameter set C resulted in a temperature increase of only 8.20 ± 0.53 °C after ten surface scans. The microbiological study showed that all irradiation parameter sets achieved a complete bacterial reduction (99.9999% or 6-log10) after ten consecutive scans, however only parameter set C did not exceed the temperature threshold. A 445 nm diode laser can be used to decontaminate dental titanium rods, and repeated laser irradiation of the contaminated areas increases the antimicrobial effect of the treatment; however, the correct choice of parameters is needed to provide adequate laser fluence while preventing an implant's temperature increase that could cause damage to the surrounding tissue.

3D printing of heart valves.

3D printing technologies have the potential to revolutionize the manufacture of heart valves through the ability to create bespoke, complex constructs. In light of recent technological advances, we review the progress made towards 3D printing of heart valves, focusing on studies that have utilised these technologies beyond manufacturing patient-specific moulds. We first overview the key requirements of a heart valve to assess functionality. We then present the 3D printing technologies used to engineer heart valves. By referencing International Organisation for Standardisation (ISO) Standard 5840 (Cardiovascular implants - Cardiac valve prostheses), we provide insight into the achieved functionality of these valves. Overall, 3D printing promises to have a significant positive impact on the creation of artificial heart valves and potentially unlock full complex functionality.

Incorporation of Controlled Release Systems Improves the Functionality of Biodegradable 3D Printed Cardiovascular Implants.

New horizons in cardiovascular research are opened by using 3D printing for biodegradable implants. This additive manufacturing approach allows the design and fabrication of complex structures according to the patient's imaging data in an accurate, reproducible, cost-effective, and quick manner. Acellular cardiovascular implants produced from biodegradable materials have the potential to provide enough support for in situ tissue regeneration while gradually being replaced by neo-autologous tissue. Subsequently, they have the potential to prevent long-term complications. In this Review, we discuss the current status of 3D printing applications in the development of biodegradable cardiovascular implants with a focus on design, biomaterial selection, fabrication methods, and advantages of implantable controlled release systems. Moreover, we delve into the intricate challenges that accompany the clinical translation of these groundbreaking innovations, presenting a glimpse of potential solutions poised to enable the realization of these technologies in the realm of cardiovascular medicine.

Carbon nanotubes as a nitric oxide nano-reservoir improved the controlled release profile in 3D printed biodegradable vascular grafts.

Small diameter vascular grafts (SDVGs) are associated with a high failure rate due to poor endothelialization. The incorporation of a nitric oxide (NO) releasing system improves biocompatibility by using the NO effect to promote endothelial cell (EC) migration and proliferation while preventing bacterial infection. To circumvent the instability of NO donors and to prolong NO releasing, S-nitroso-N-acetyl-D-penicillamine (SNAP) as a NO donor was loaded in multi-walled carbon nanotubes (MWCNTs). Successful loading was confirmed with a maximum SNAP amount of ~ 5% (w/w) by TEM, CHNS analysis and FTIR spectra. SDVGs were 3D printed from polycaprolactone (PCL) and coated with a 1:1 ratio of polyethylene glycol and PCL dopped with different concentrations of SNAP-loaded matrix and combinations of MWCNTs-OH. Coating with 10% (w/w) SNAP-matrix-10% (w/w) SNAP-MWCNT-OH showed a diminished burst release and 18 days of NO release in the range of 0.5-4 × 10-10 mol cm-2 min-1 similar to the NO release from healthy endothelium. NO-releasing SDVGs were cytocompatible, significantly enhanced EC proliferation and migration and diminished bacterial viability. The newly developed SNAP-loaded MWCNT-OH has a great potential to develop NO releasing biomaterials with a prolonged, controlled NO release promoting in-situ endothelialization and tissue integration in vivo, even as an approach towards personalized medicine.

A Mucin-Based Bio-Ink for 3D Printing of Objects with Anti-Biofouling Properties.

With its potential to revolutionize the field of personalized medicine by producing customized medical devices and constructs for tissue engineering at low costs, 3D printing has emerged as a highly promising technology. Recent advancements have sparked increasing interest in the printing of biopolymeric hydrogels. However, owing to the limited printability of those soft materials, the lack of variability in available bio-inks remains a major challenge. In this study, a novel bio-ink is developed based on functionalized mucin-a glycoprotein that exhibits a multitude of biomedically interesting properties such as immunomodulating activity and strong anti-biofouling behavior. To achieve sufficient printability of the mucin-based ink, its rheological properties are tuned by incorporating Laponite XLG as a stabilizing agent. It is shown that cured objects generated from this novel bio-ink exhibit mechanical properties partially similar to that of soft tissue, show strong anti-biofouling properties, good biocompatibility, tunable cell adhesion, and immunomodulating behavior. The presented findings suggest that this 3D printable bio-ink has a great potential for a wide range of biomedical applications, including tissue engineering, wound healing, and soft robotics.

Dopamine-Mediated Biopolymer Multilayer Coatings for Modulating Cell Behavior, Lubrication, and Drug Release.

Biopolymer coatings on implants mediate the interactions between the synthetic material and its biological environment. Owing to its ease of preparation and the possibility to incorporate other bioactive molecules, layer-by-layer deposition is a method commonly used in the construction of biopolymer multilayers. However, this method typically requires at least two types of oppositely charged biopolymers, thus limiting the range of macromolecular options by excluding uncharged biopolymers. Here, we present a layer-by-layer approach that employs mussel-inspired polydopamine as the adhesive intermediate layer to build biopolymer multilayer coatings without requiring any additional chemical modifications. We select three biopolymers with different charge states─anionic alginate, neutral dextran, and cationic polylysine─and successfully assemble them into mono-, double-, or triple-layers. Our results demonstrate that both the layer number and the polymer type modulate the coating properties. Overall, increasing the number of layers in the coatings leads to reduced cell attachment, lower friction, and higher drug loading capacity but does not alter the surface potential. Moreover, varying the biopolymer type affects the surface potential, macrophage differentiation, lubrication performance, and drug release behavior. This proof-of-concept study offers a straightforward and universal coating method, which may broaden the use of multilayer coatings in biomedical applications.

Analysis of flow-induced transcriptional response and cell alignment of different sources of endothelial cells used in vascular tissue engineering.

Endothelialization of tissue-engineered vascular grafts has proven crucial for implant functionality and thus clinical outcome, however, the choice of endothelial cells (ECs) is often driven by availability rather than by the type of vessel to be replaced. In this work we studied the response to flow of different human ECs with the aim of examining whether their response in vitro is dictated by their original in vivo conditions. Arterial, venous, and microvascular ECs were cultured under shear stress (SS) of 0, 0.3, 3, 1, 10, and 30 dyne/cm2 for 24 h. Regulation of flow-induced marker KLF2 was similar across the different ECs. Upregulation of anti-thrombotic markers, TM and TPA, was mainly seen at higher SS. Cell elongation and alignment was observed for the different ECs at 10 and 30 dyne/cm2 while at lower SS cells maintained a random orientation. Downregulation of pro-inflammatory factors SELE, IL8, and VCAM1 and up-regulation of anti-oxidant markers NQO1 and HO1 was present even at SS for which cell alignment was not observed. Our results evidenced similarities in the response to flow among the different ECs, suggesting that the maintenance of the resting state in vitro is not dictated by the SS typical of the tissue of origin and that absence of flow-induced cell orientation does not necessarily correlate with a pro-inflammatory state of the ECs. These results support the use of ECs from easily accessible sources for in vitro vascular tissue engineering independently from the target vessel.

A Feature-Specific Local Cooling System to Control Tensile Strength and Dimensional Accuracy in Fused Filament Fabrication.

There is in-depth understanding of the effects and interactions of various process parameters on the mechanical properties and dimensional accuracy of parts produced through fused filament fabrication (FFF). Surprisingly, local cooling in FFF has been largely overlooked and is only rudimentarily implemented. It is, however, a decisive element of the thermal conditions governing the FFF process and of particular importance when processing high-temperature polymers such as polyether ether ketone (PEEK). This study, therefore, proposes an innovative local cooling strategy, which allows for feature-specific local cooling (FLoC). This is enabled by a newly developed hardware in combination with a G-code postprocessing script. The system was implemented on a commercially available FFF printer and its potential was demonstrated by addressing typical drawbacks of the FFF process. Specifically, with FLoC, the conflicting requirements for optimal tensile strength versus optimal dimensional accuracy could be balanced. Indeed, feature-specific (i.e., perimeter vs. infill) control of thermal conditions resulted in a significant increase in ultimate tensile strength and in strain at failure in upright printed PEEK tensile bars compared with those manufactured with constant local cooling-without sacrificing the dimensional accuracy. Furthermore, to improve the surface quality of downward-facing structures the controlled introduction of predetermined breaking points at feature-specific part/support interfaces was demonstrated. The findings of this study prove the importance and capabilities of the new advanced local cooling system in high-temperature FFF and provide further directions on the process development of FFF in general.

The colonoscopic vacuum model-simulating biomechanical restrictions to provide a realistic colonoscopy training environment.

INTRODUCTION: Practicing endoscopic procedures is fundamental for the education of clinicians and the benefit of patients. Despite a diverse variety of model types, there is no system simulating anatomical restrictions and variations in a flexible and atraumatic way. Our goal was to develop and validate a new modelling approach for adhesion forces between colon and abdominal wall. METHODS: An inlay for a standard mechanical trainer was designed and 3D printed. Colon specimens were fixed to the inlay along colon ascendens (CA) and colon descendens (CD) by a vacuum. Our system, which we refer to as Colonoscopy Vacuum Model (CoVaMo), was validated with 11 test persons with varying level of expertise. Each performed one colonoscopy and one polypectomy in the CoVaMo and in the Endoscopic Laparoscopic Interdisciplinary Training Entity (ELITE). Achieved adhesion forces, times required to fulfill different tasks endoscopically and a questionnaire, assessing proximity to reality, were recorded. RESULTS: Mean adhesion forces of 37 ± 7 N at the CA and 30 ± 15 N at the CD were achieved. Test subjects considered CoVaMo more realistic than ELITE concerning endoscope handling and the overall anatomy. Participants needed statistically significantly more time to maneuver from anus to flexura sinistra in CoVaMo (377 s ± 244 s) than in ELITE (58 s ± 49 s). CONCLUSION: We developed a training environment enabling anatomically and procedural realistic colonoscopy training requiring participants to handle all endoscope features in parallel. Fixation forces compare to forces needed to tear pig colon off the mesentery. Workflow and inlay can be adapted to any arbitrary ex vivo simulator.

New perspectives in patient education for cardiac surgery using 3D-printing and virtual reality.

Background: Preoperative anxiety in cardiac surgery can lead to prolonged hospital stays and negative postoperative outcomes. An improved patient education using 3D models may reduce preoperative anxiety and risks associated with it. Methods: Patient education was performed with standardized paper-based methods (n = 34), 3D-printed models (n = 34) or virtual reality models (n = 31). Anxiety and procedural understanding were evaluated using questionnaires prior to and after the patient education. Additionally, time spent for the education and overall quality were evaluated among further basic characteristics (age, gender, medical expertise, previous non-cardiac surgery and previously informed patients). Included surgeries were coronary artery bypass graft, surgical aortic valve replacement and thoracic aortic aneurysm surgery. Results: A significant reduction in anxiety measured by Visual Analog Scale was achieved after patient education with virtual reality models (5.00 to 4.32, Δ-0.68, p < 0.001). Procedural knowledge significantly increased for every group after the patient education while the visualization and satisfaction were best rated for patient education with virtual reality. Patients rated the quality of the patient education using both visualization methods individually [3D and virtual reality (VR) models] higher compared to the control group of conventional paper-sheets (control paper-sheets: 86.32 ± 11.89%, 3D: 94.12 ± 9.25%, p < 0.0095, VR: 92.90 ± 11.01%, p < 0.0412). Conclusion: Routine patient education with additional 3D models can significantly improve the patients' satisfaction and reduce subjective preoperative anxiety effectively.

The effects of surface treatments on electron beam melted Ti-6Al-4V disks on osteogenesis of human mesenchymal stromal cells.

Additive manufactured (AM) Titanium-6Aluminum-4Vanadium (Ti64) scaffolds display unique mechanical and biological properties for implant devices. The elastic modulus can be tailored by adjusting the porosity, further facilitating bone ingrowth. Although Ti64 implants are biocompatible, the effects of AM surfaces without porous structures, and how the topography and surface chemistry of the respective surfaces affect the osteogenesis of bone marrow-derived mesenchymal stromal cells (BMSCs) has not yet been revealed. In this paper, we cultured BMSCs on solid electron beam melted Ti64 disks subjected to three surface treatments: chemical etching (HF), atomic-layer deposition of TiO2 (TiO2), and polished (POL), or left untreated (AB). The biocompatibility and osteogenic properties of these surfaces were investigated, and the results were compared to cells cultured in regular tissue-culture polystyrene culturing wells (TCPS). The surfaces were hydrophobic, except for the polished surface which was hydrophilic. All surface treatments are biocompatible and allow for osteogenic differentiation, as revealed by viability assays and gene expression analysis. Scanning electron microscopy shows that cells adhere differently depending on the surface properties, with more filopodia on the rougher surfaces, AB and TiO2 disks, and more lamellipodia on the smoother surfaces, HF and POL disks. All groups stimulated with beta glycerophosphate, ascorbic acid, and dexamethasone, have elevated expression of genes related to matrix formation, where the cells cultured on the disks treated with TiO2, HF and POL have the overall highest expression. The AB group appears to be less favorable in regards to matrix formation. Considering the matrix mineralization, the rougher surfaces, AB and TiO2, are able to induce matrix mineralization, with an elevated gene expression of vitamin D receptors and calcium deposition of unstimulated cells. Finally, imaging at day 21 revealed an even amount of cells and matrix, covering most of the partially melted particles. Our results suggests that surface topography is more important to osteogenesis than the wettability of the surface. Overall, the present study contributes to the understanding of using surface modifications to AM Ti64 implant materials and reveals how they affect bone growth.

Application of magnetic iron oxide nanoparticles: Thrombotic activity, imaging and cytocompatibility of silica-coated and carboxymethyl dextrane-coated particles.

Coated iron oxide nanoparticles (IONs) are promising candidates for various applications in nanomedicine, including imaging, magnetic hyperthermia, and drug delivery. The application of IONs in nanomedicine is influenced by factors such as biocompatibility, surface properties, agglomeration, degradation behavior, and thrombogenicity. Therefore, it is essential to investigate the effects of coating material and thickness on the behavior and performance of IONs in the human body. In this study, IONs with a carboxymethyl dextran (CMD) coating and two thicknesses of silica coating (TEOS0.98, and TEOS3.91) were screened and compared to bare iron oxide nanoparticles (BIONs). All three coated particles showed good cytocompatibility (>70%) when tested with smooth muscle cells over three days. To investigate their potential long term behavior inside the human body, the Fe2+ release and hydrodynamic diameters of silica-coated and CMD (carboxymethyl dextrane)-coated IONs were analyzed in simulated body fluids for 72 h at 37 °C. The ION@CMD showed moderate agglomeration of around 100 nm in all four simulated fluids and dissolved faster than the silica-coated particles in artificial exosomal fluid and artificial lysosomal fluid. The particles with silica coating agglomerated in all tested simulated media above 1000 nm. Increased thickness of the silica coating led to decreased degradation of particles. Additionally, CMD coating resulted in nanoparticles with the least prothrombotic activity, and the thick silica coating apparently decreased the prothrombotic properties of nanoparticles compared to BIONs and ION@TEOS0.98. For magnetic resonance applications, ION@CMD and ION@TEOS3.91 showed comparatively high relaxation rates R2 values. In magnetic particle imaging experiments ION@TEOS3.91 yielded the highest normalized signal to noise ratio values and in magnetic hyperthermia studies, ION@CMD and ION@TEOS0.98 showed similar specific loss power. These findings demonstrate the potential of coated IONs in nanomedicine and emphasize the importance of understanding the effect of coating material and thickness on their behavior and performance in the human body.

Development of a Silk Fibroin-Small Intestinal Submucosa Small-Diameter Vascular Graft with Sequential VEGF and TGF-ß1 Inhibitor Delivery for In Situ Tissue Engineering.

Proper endothelialization and limited collagen deposition on the luminal surface after graft implantation plays a crucial role to prevent the occurrence of stenosis. To achieve these conditions, a biodegradable graft with adequate mechanical properties and the ability to sequentially deliver therapeutic agents isfabricated. In this study, a dual-release system is constructed through coaxial electrospinning by incorporating recombinant human vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) inhibitor into silk fibroin (SF) nanofibers to form a bioactive membrane. The functionalized SF membrane as the inner layer of the graft is characterized by the release profile, cell proliferation and protein expression. It presents excellent biocompatibility and biodegradation, facilitating cell attachment, proliferation, and infiltration. The core-shell structure enables rapid VEGF release within 10 days and sustained plasmid delivery for 21 days. A 2.0-mm-diameter vascular graft is fabricated by integrating the SF membrane with decellularized porcine small intestinal submucosa (SIS), aiming to facilitate the integration process under a stable extracellular matrix structure. The bioengineered graft is functionalized with the sequential administration of VEGF and TGF-ß1, and with the reinforced and compatible mechanical properties, thereby offers an orchestrated solution for stenosis with potential for in situ vascular tissue engineering applications.

Impact of left atrial appendage occlusion device position on potential determinants of device-related thrombus: a patient-specific in silico study.

BACKGROUND: Device-related thrombus (DRT) after left atrial appendage occlusion (LAAO) is potentially linked to adverse events. Although clinical reports suggest an effect of the device type and position on the DRT risk, in-depth studies of its mechanistic basis are needed. This in silico study aimed to assess the impact of the position of non-pacifier (Watchman) and pacifier (Amulet) LAAO devices on surrogate markers of DRT risk. METHODS: The LAAO devices were modeled with precise geometry and virtually implanted in different positions into a patient-specific left atrium. Using computational fluid dynamics, the following values were quantified: residual blood, wall shear stress (WSS) and endothelial cell activation potential (ECAP). RESULTS: In comparison to an ostium-fitted device position, deep implantation led to more residual blood, lower average WSS and higher ECAP surrounding the device, especially on the device's atrial surface and the surrounding tissue, suggesting increased risk for potential thrombus. For the non-pacifier device, an off-axis device orientation resulted in even more residual blood, higher ECAP and similar average WSS as compared to an ostium-fitted device position. Overall, the pacifier device showed less residual blood, higher average WSS and lower ECAP, compared to the non-pacifier device. CONCLUSIONS: In this in silico study, both LAAO device type and implant position showed an impact on potential markers of DRT in terms of blood stasis, platelet adhesion and endothelial dysfunction. Our results present a mechanistic basis for clinically observed risk factors of DRT and the proposed in silico model may aid in the optimization of device development and procedural aspects.

Superparamagnetic iron oxide nanoparticles for their application in the human body: Influence of the surface.

Iron oxide nanoparticles (IONs) are of great interest in nanomedicine for imaging, drug delivery, or for hyperthermia treatment. Although many research groups have focused on the synthesis and application of IONs in nanomedicine, little is known about the influence of the surface properties on the particles' behavior in the human body. This study analyzes the impact of surface coatings (dextran, polyvinyl alcohol, polylactide-co-glycolide) on the nanoparticles' cytocompatibility, agglomeration, degradation, and the resulting oxidative stress induced by the particle degradation. All particles, including bare IONs (BIONs), are highly cytocompatible (>70%) and show no significant toxicity towards smooth muscle cells. Small-angle X-ray scattering profiles visualize the aggregation behavior of nanoparticles and yield primary particle sizes of around 20 nm for the investigated nanoparticles. A combined experimental setup of dynamic light scattering and phenanthroline assay was used to analyze the long-term agglomeration and degradation profile of IONs in simulated body fluids, allowing fast screening of multiple candidates. All particles degraded in simulated endosomal and lysosomal fluid, confirming the pH-dependent dissolution. The degradation rate decreased with the shrinking size of particles leading to a plateau. The fastest Fe2+ release could be measured for the polyvinyl-coated IONs. The analytical setup is ideal for a quick preclinical study of IONs, giving often neglected yet crucial information about the behavior and toxicity of nanoparticles in the human body. Moreover, this study allows for the development and evaluation of novel ferroptosis-inducing agents.

4D Printing Applications in the Development of Smart Cardiovascular Implants.

Smart materials are able to react to different stimuli and adapt their shape to the environment. Although the development of 3D printing technology increased the reproducibility and accuracy of scaffold fabrication, 3D printed scaffolds can still be further improved to resemble the native anatomy. 4D printing is an innovative fabrication approach combining 3D printing and smart materials, also known as stimuli-responsive materials. Especially for cardiovascular implants, 4D printing can promisingly create programmable, adaptable prostheses, which facilitates implantation and/or create the topology of the target tissue post implantation. In this review, the principles of 4D printing with a focus on the applied stimuli are explained and the underlying 3D printing technologies are presented. Then, according to the type of stimulus, recent applications of 4D printing in constructing smart cardiovascular implants and future perspectives are discussed.

Electromagnetic tool for the endoscopic creation of colon anastomoses-development and feasibility assessment of a novel anastomosis compression implant approach.

BACKGROUND: Colorectal anastomoses are among the most commonly performed interventions in abdominal surgery, while associated patient trauma is still high. Most recent trends of endoscopic anastomosis devices integrate magnetic components to overcome the challenges of minimally invasive surgery. However, the mutual attraction between magnetic implant halves may increase the risk of inadvertently pinching healthy structures. Thus, we present a novel anastomosis device to improve system controllability and flexibility. METHODS: A magnetic implant and an applicator with electromagnetic control units were developed. The interaction of magnetic implants with the electromagnets bears particular challenges with respect to the force-related dimensioning. Here, attraction forces must be overcome by the electromagnet actuation to detach the implant, while the attraction force between the implant halves must be sufficient to ensure a stable connection. Thus, respective forces were measured and the detachment process was reproducibly investigated. Patient hazards, associated with resistance-related heating of the coils were investigated. RESULTS: Anastomosis formation was reproducibly successful for an implant, with an attraction force of 1.53 [Formula: see text], resulting in a compression pressure of [Formula: see text]. The implant was reproducibly detachable from the applicator at the anastomosis site. Coils heated up to a maximum temperature of [Formula: see text]. Furthermore, we were able to establish a neat reconnection of intestinal bowel endings using our implant. DISCUSSION: As we achieved nearly equal compression forces with our implant as other magnetic anastomosis systems did (Magnamosis™: 1.48 N), we concluded that our approach provides sufficient holding strength to counteract the forces acting immediately postoperatively, which would eventually lead to an undesired slipping of the implant halves during the healing phase. Based on heat transfer investigations, preventive design specifications were derived, revealing that the wall thickness of a polymeric isolation is determined rather by stability considerations, than by heat shielding requirements.