Dual Cross-Linked Stimuli-Responsive Alginate-Based Hydrogels.

Sodium alginate with different molecular weights (55, 170, and 320 kg mol-1) were chemically modified by grafting methacrylic moieties onto the hydroxyl groups of the alginate backbone. The methacrylation was optimized to obtain different degrees of modification. Chemically cross-linked hydrogels were obtained following UV-light irradiation in the presence of a photoinitiator. The swelling behavior and the mechanical properties were observed to depend on both the degree of methacrylation and the alginate molecular weight. Due to the chain entanglement present in high-viscosity sodium alginate, lower degrees of modification were required to tune the hydrogel properties. Moreover, in the presence of Ca2+, secondary cross-linking was introduced by the coordination of the alginate guluronate moieties with the Ca2+ ions. The addition of this secondary cross-linking caused fast volume shrinkage and a reinforcement of the mechanical properties. The secondary cross-linking was reversible, and the hydrogels regained their original shape for at least three cycles. Additionally, the dual cross-linked network can be used to induce adhesion between hydrogels and serve as a building block for self-folding actuators.

Polyoxazoline hydrogels fabricated by stereolithography.

The development of hydrogel materials in additive manufacturing displaying stiff and strong mechanical properties while maintaining high water uptake remains a great challenge. Taking advantage of the versatility of poly(oxazoline) (POx) chemistry and properties, we investigated in this article a new generation of POx hydrogels fabricated by stereolithography (SLA). A large range of photosensitive poly(2-methyl-2-oxazoline) resins were synthesized as hydrogel precursors for SLA photofabrication. Functionalization has been performed by direct di-methacrylation of POx terminal groups (MA2POxn) or by multi-methacrylation of poly(ethyleneimine) (PEI) units resulting from partial POx hydrolysis (MAmPOxn-PEIp). The length and the functionality of these UV-active macro-crosslinkers influence both the mechanical properties and the hydration behavior of the resulting hydrogels. The benefit of the layer-by-layer crosslinking of the POx resin during the vat photopolymerization allowed the fabrication of complex and well-defined 3D objects. The high-definition and high mechanical strength of these copolymers allow the fabrication of stiff and strong 3D hydrogels. The cytocompatibility test of the POx derivatives was conducted in solution and once the cells are encapsulated within 3D hydrogels. Finally, porous 3D scaffolds with gyroid architectures were built which provide opportunities for POx materials in tissue engineering applications.

Photoprintable Gelatin-graft-Poly(trimethylene carbonate) by Stereolithography for Tissue Engineering Applications.

The stereolithography process is a powerful additive manufacturing technology to fabricate scaffolds for regenerative medicine. Nevertheless, the quest for versatile inks allowing one to produce scaffolds with controlled properties is still unsatisfied. In this original article, we tackle this bottleneck by synthesizing a panel of photoprocessable hybrid copolymers composed of gelatin-graft-poly(trimethylene carbonate)s (Gel-g-PTMCn). We demonstrated that by changing the length of PTMC blocks grafted from gelatin, it is possible to tailor the final properties of the photofabricated objects. We reported here on the synthesis of Gel-g-PTMCn with various lengths of PTMC blocks grafted from gelatin using hydroxy and amino side groups of the constitutive amino acids. Then, the characterization of the resulting hybrid copolymers was fully investigated by quantitative NMR spectroscopy before rendering them photosensitive by methacrylation of the PTMC terminal groups. Homogeneous composition of the photocrosslinked hybrid polymers was demonstrated by EDX spectroscopy and electronic microscopy. To unravel the individual contribution of the PTMC moiety on the hybrid copolymer behavior, water absorption, contact angle measurements, and degradation studies were undertaken. Interestingly, the photocrosslinked materials immersed in water were examined using tensile experiments and displayed a large panel of behavior from hydrogel to elastomer-like depending on the PTMC/gel ratio. Moreover, the absence of cytotoxicity was conducted following the ISO 10993 assay. As a proof of concept, 3D porous objects were successfully fabricated using stereolithography. Those results validate the great potential of this panel of inks for tissue engineering and regenerative medicine.

Synthesis of Poly(Trimethylene Carbonate) from Amine Group Initiation: Role of Urethane Bonds in the Crystallinity.

Semi-crystalline poly(trimethylene carbonate) (PTMC) can be efficiently prepared by ring-opening polymerization (ROP) initiated by amine using various catalysts. More promising results were reached with the one-step process of stannous octanoate unlike the two-step one-pot reaction using TBD and MSA catalysts. The ROP-amine of TMC consists in a simple isocyanate free process to produce polycarbonate-urethanes, compatible with the large availability of amines ranging from mono- to multifunctional until natural amino acids. ROP-amine of TMC leads to urethane bonds monitored by FTIR spectroscopy. The relationship between the nature of amines and the crystallinity of PTMC was discussed through X-ray diffraction and thermal studies by DSC and TGA. The impact of the crystallinity was also demonstrated on the mechanical properties of semi-crystalline PTMC in comparison to amorphous PTMC, synthesized by ROP initiated by alcohol. The semi-crystalline PTMC synthesized by ROP-amine opens many perspectives.

Triply Periodic Minimal Surfaces (TPMS) for the Generation of Porous Architectures Using Stereolithography.

A new generation of sophisticated tissue engineering scaffolds are developed using the periodicity of trigonometric equations to generate triply periodic minimal surfaces (TPMS). TPMS architectures display minimal surface energy that induce typical pore features and surface curvatures. Here we described a series of TPMS geometries and developed a procedure to build such scaffolds by stereolithography using biocompatible and biodegradable photosensitive resins.

Engineering 3D parallelized microfluidic droplet generators with equal flow profiles by computational fluid dynamics and stereolithographic printing.

Microfluidic droplet generators excel in generating monodisperse micrometer-sized droplets and particles. However, the low throughput of conventional droplet generators hinders their clinical and industrial translation. Current approaches to parallelize microdevices are challenged by the two-dimensional nature of the standard fabrication methods. Here, we report the facile production of three-dimensionally (3D) parallelized microfluidic droplet generators consisting of stacked and radially multiplexed channel designs. Computational fluid dynamics simulations form the design basis for a microflow distributor that ensures similar flow rates through all droplet generators. Stereolithography is the selected technique to fabricate microdevices, which enables the manufacturing of hollow channels with dimensions as small as 50 µm. The microdevices could be operated up to 4 bars without structural damage, including deformation of channels, or leakage of the on-chip printed Luer-Lok type connectors. The printed microdevices readily enable the production of water-in-oil emulsions, as well as polymer containing droplets that act as templates for both solid and core-shell hydrogel microparticles. The cytocompatibility of the 3D printed device is demonstrated by encapsulating mesenchymal stem cells in hydrogel microcapsules, which results in the controllable formation of stem cell spheroids that remain viable and metabolically active for at least 21 days. Thus, the unique features of stereolithography fabricated microfluidic devices allow for the parallelization of droplet generators in a simple yet effective manner by enabling the realization of (complex) 3D designs.

Zwitterionic Functionalizable Scaffolds with Gyroid Pore Architecture for Tissue Engineering.

Stereolithography-assisted fabrication of hydrogels of carboxybetaine methacrylamide (CBMAA) and a α,ω-methacrylate poly(d,l-lactide-block-ethylene glycol-block- d,l-lactide) (MA-PDLLA-PEG-PDLLA-MA) telechelic triblock macromer is presented. This technique allows printing complex structures with gyroid interconnected porosity possessing extremely high specific area. Hydrogels are characterized by infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and laser scanning confocal microscopy (LSCM). The copolymerization with zwitterionic comonomer leads hydrogels with high equilibrium water content (EWC), up to 700% while maintaining mechanical robustness. The introduction of carboxybetaine yields excellent resistance to nonspecific protein adsorption while providing a facile way for specific biofunctionalization with a model protein, fluorescein isothiocyanate labeled bovine serum albumin (BSA). The homogeneous protein immobilization across the hydrogel pores prove the accessibility to the innermost pore volumes. The remarkably low protein adsorption combined with the interconnected nature of the porosity allowing fast diffusion of nutrient and waste product and the mimicry of bone trabecular, makes the hydrogels presented here highly attractive for tissue engineering.

Surface curvature in triply-periodic minimal surface architectures as a distinct design parameter in preparing advanced tissue engineering scaffolds.

Reproduction of the anatomical structures and functions of tissues using cells and designed 3D scaffolds is an ongoing challenge. For this, scaffolds with appropriate biomorphic surfaces promoting cell attachment, proliferation and differentiation are needed. In this study, eight triply-periodic minimal surface (TPMS)-based scaffolds were designed using specific trigonometric equations, providing the same porosity and the same number of unit cells, while presenting different surface curvatures. The scaffolds were fabricated by stereolithography using a photocurable resin based on the biocompatible, biodegradable and rubber-like material, poly(trimethylene carbonate) (PTMC). A numerical approach was developed to calculate the surface curvature distributions of the TPMS architectures. Moreover, the scaffolds were characterized by scanning electron microscopy, micro-computed tomography and water permeability measurements. These original scaffold architectures will be helpful to decipher the biofunctional role of the surface curvature of scaffolds intended for tissue engineering applications.

Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation.

Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials. Here, the role of surface curvature on the migratory and differentiation behavior of human mesenchymal stem cells (hMSCs) has been investigated on 3D surfaces with well-defined geometric features produced by stereolithography. Time lapse microscopy reveals a significant increase of cell migration speed on concave spherical compared to convex spherical structures and flat surfaces resulting from an upward-lift of the cell body due to cytoskeletal forces. On convex surfaces, cytoskeletal forces lead to substantial nuclear deformation, increase lamin-A levels and promote osteogenic differentiation. The findings of this study demonstrate a so far missing link between 3D surface curvature and hMSC behavior. This will not only help to better understand the role of extracellular matrix architecture in health and disease but also give new insights in how 3D geometries can be used as a cell-instructive material parameter in the field of biomaterial-guided tissue regeneration.

Differentiation of adipose stem cells seeded towards annulus fibrosus cells on a designed poly(trimethylene carbonate) scaffold prepared by stereolithography.

Cell-based therapies could potentially restore the biomechanical function and enhance the self-repair capacity of annulus fibrosus (AF) tissue. However, choosing a suitable cell source and scaffold design are still key challenges. In this study, we assessed the in vitro ability of human adipose stem cells (hASCs), an easily available cell source to produce AF-like matrix in novel AF-mimetic designed scaffolds based on poly(trimethylene carbonate) and built by stereolithography. To facilitate efficient differentiation of hASCs towards AF tissue, we tested different culture medium compositions and cell seeding techniques. This is the first study to report that medium supplementation with transforming growth factor (TGF)-ß3 is essential to support AF differentiation of hASCs while TGF-ß1 has negligible effect after 21 days of culture. Fibrin gel seeding resulted in superior cell distribution, proliferation and AF-like matrix production of hASCs compared to direct and micromass seeding under TGF-ß3 stimulation. Not only the production of sulphated glycosaminoglycans (sGAG) and collagen was significantly upregulated, but the formed collagen was also oriented and aligned into bundles within the designed pore channels. The differentiated hASCs seeded with fibrin gel were also found to have a comparable sGAG:collagen ratio and gene expression profile as native AF cells demonstrating the high potential of this strategy in AF repair. Copyright © 2016 John Wiley & Sons, Ltd.

Nanoparticles as contrast agents for brain nuclear magnetic resonance imaging in Alzheimer's disease diagnosis.

Nuclear Magnetic Resonance Imaging (MRI) of amyloid plaques is a powerful non-invasive approach for the early and accurate diagnosis of Alzheimer's disease (AD) along with clinical observations of behavioral changes and cognitive impairment. The present article aims at giving a critical and comprehensive review of recent advances in the development of nanoparticle-based contrast agents for brain MRI. Nanoparticles considered for the MRI of AD must comply with a highly stringent set of requirements including low toxicity and the ability to cross the blood-brain-barrier. In addition, to reach an optimal signal-to-noise ratio, they must exhibit a specific ability to target amyloid plaques, which can be achieved by grafting antibodies, peptides or small molecules. Finally, we propose to consider new directions for the future of MRI in the context of Alzheimer's disease, in particular by enhancing the performances of contrast agents and by including therapeutic functionalities following a theranostic strategy.

Mechanical restoration and failure analyses of a hydrogel and scaffold composite strategy for annulus fibrosus repair.

Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disk height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disk biomechanics with low herniation risk, suggesting further evaluation for disk repair may be warranted. STATEMENT OF SIGNIFICANCE: Lower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered during surgical procedures. This work addressed this challenging biomaterial and clinical problem using novel materials including an adhesive hydrogel, a scaffold capable of cell delivery, and a membrane to prevent herniation. Composite repair strategies were evaluated and optimized in quantitative three-part study that rigorously evaluated disk repair and provided a framework for evaluating alternate repair techniques.

µCT based assessment of mechanical deformation of designed PTMC scaffolds.

BACKGROUND: Advances in rapid-prototyping and 3D printing technologies have enhanced the possibilities in preparing designed architectures for tissue engineering applications. A major advantage in custom designing is the ability to create structures with desired mechanical properties. While the behaviour of a designed scaffold can be simulated using bulk material properties, it is important to verify the behaviour of a printed scaffold at the microstructure level. OBJECTIVE: In this study we present an effective method in validating the mechanical behaviour of designed scaffolds using a µCT with an in-situ mechanical deformation device. METHODS: The scaffolds were prepared from biodegradable poly(trimethylene carbonate) (PTMC) by stereolithography and images obtained using a high-resolution µCT with 12.25µm isometric voxels. The data was processed (filtering, segmentation) and analysed (surface generation, registration) to extract relevant deformation features. RESULTS: The computed local deformation fields, calculated at sub-pore resolutions, displayed expected linear behaviour within the scaffold along the compressions axis. On planes perpendicular to this axis, the deformations varied by 150- 200µm. CONCLUSIONS: µCT based imaging with in-situ deformation provides a vital tool in validating the design parameters of printed scaffolds. Deformation fields obtained from micro-tomographic image volumes can serve to corroborate the simulated ideal design with the realized product.

Tolerance and long-term MRI imaging of gadolinium-modified meshes used in soft organ repair.

BACKGROUND: Synthetic meshes are frequently used to reinforce soft tissues. The aim of this translational study is to evaluate tolerance and long-term MRI visibility of two recently developed Gadolinium-modified meshes in a rat animal model. MATERIALS AND METHODS: Gadolinium-poly-ε-caprolactone (Gd-PCL) and Gadolinium-polymethylacrylate (Gd-PMA) modified meshes were implanted in Wistar rats and their tolerance was assessed daily. Inflammation and biocompatibility of the implants were assessed by histology and immunohistochemistry after 30 days post implantation. Implants were visualised by 7T and 3T MRI at day 30 and at day 90. Diffusion of Gadolinium in the tissues of the implanted animals was assessed by Inductively Coupled Plasma Mass Spectrometry. RESULTS: Overall Gd-PMA coated implants were better tolerated as compared to those coated with Gd-PCL. In fact, Gd-PMA implants were characterised by a high ratio collagen I/III and good vascularisation of the integration tissues. High resolution images of the coated mesh were obtained in vivo with experimental 7T as well as 3T clinical MRI. Mass spectrometry analyses showed that levels of Gadolinium in animals implanted with coated mesh were similar to those of the control group. CONCLUSIONS: Meshes coated with Gd-PMA are better tolerated as compared to those coated with Gd-PCL as no signs of erosion or significant inflammation were detected at 30 days post implantation. Also, Gd-PMA coated meshes were clearly visualised with both 7T and 3T MRI devices. This new technique of mesh optimisation may represent a valuable tool in soft tissue repair and management.

A combined biomaterial and cellular approach for annulus fibrosus rupture repair.

Recurrent intervertebral disc (IVD) herniation and degenerative disc disease have been identified as the most important factors contributing to persistent pain and disability after surgical discectomy. An annulus fibrosus (AF) closure device that provides immediate closure of the AF rupture, restores disc height, reduces further disc degeneration and enhances self-repair capacities is an unmet clinical need. In this study, a poly(trimethylene carbonate) (PTMC) scaffold seeded with human bone marrow derived mesenchymal stromal cells (MSCs) and covered with a poly(ester-urethane) (PU) membrane was assessed for AF rupture repair in a bovine organ culture annulotomy model under dynamic load for 14 days. PTMC scaffolds combined with the sutured PU membrane restored disc height of annulotomized discs and prevented herniation of nucleus pulposus (NP) tissue. Implanted MSCs showed an up-regulated gene expression of type V collagen, a potential AF marker, indicating in situ differentiation capability. Furthermore, MSCs delivered within PTMC scaffolds induced an up-regulation of anabolic gene expression and down-regulation of catabolic gene expression in adjacent native disc tissue. In conclusion, the combined biomaterial and cellular approach has the potential to hinder herniation of NP tissue, stabilize disc height, and positively modulate cell phenotype of native disc tissue.

Development of poly(trimethylene carbonate) network implants for annulus fibrosus tissue engineering.

PURPOSE: Intervertebral disk degeneration is the main cause of chronic back pain. Disk degeneration often leads to tearing of the annulus fibrosus (AF) and extrusion of the nucleus pulposus (NP), which compresses the nerves. Current treatment involves removing the herniated NP and suturing the damaged AF tissue. This surgical approach has several drawbacks. In this study, we designed a biodegradable AF closure system comprising a tissue engineering scaffold, a supporting membrane and an adhesive material, to not only restore the function of the herniated disc but also to promote tissue regeneration. MATERIALS AND METHODS: Porous scaffolds with precisely defined architectures were built by stereolithography using resins based on poly(trimethylene carbonate) (PTMC) macromers functionalized with methacrylate endgroups. In addition, a porous photo-cross-linked PTMC membrane was developed that can be used to keep the scaffold in place in the AF tissue. RESULTS: After synthesis and characterization, the components of the implant are glued together and to the AF tissue using a diisocyanate glue based on polyethylene glycol-PTMC triblock copolymers. The adhesion strengths of the materials to each other and to AF tissue were determined in lap-shear tests. CONCLUSIONS: This study showed that a device for AF tissue engineering can be prepared from PTMC-based scaffolds, membranes and glues.

Polymeric microstructures with shape-memory properties for biomedical use built by stereolithography.

PURPOSE: The aim of this study was to design and build porous microstructures with shape memory behaviour using biodegradable poly(D,L-lactide-co-trimethylene carbonate) dimethacrylate macromers. These microstructures could be advantageous for tissue engineering and other advanced biomedical applications. METHODS: Porous structures with a gyroid pore network architecture showing average pore sizes of 930 µm and complete pore interconnectivity were prepared by stereolithography. Built structures were characterized by Micro-computed tomography (µ-CT). Shape recovery and shape fixity of microstructures after 40% and 70% compression were evaluated. RESULTS: At 37 °C the flexible structures showed compression modulus values of 60 KPa and could be fully compressed. Thermal analysis showed that the built networks were amorphous with Tg values of 23 °C. After compression to 40 and 70%, shape fixity and shape recovery of the structures at respectively 0 °C and 37 °C was almost quantitative. CONCLUSIONS: The well-defined pore network characteristics and the shape-memory properties of these structures allow their use as deployable tissue engineering scaffolds.

Biodegradable nanocomposite hydrogel structures with enhanced mechanical properties prepared by photo-crosslinking solutions of poly(trimethylene carbonate)-poly(ethylene glycol)-poly(trimethylene carbonate) macromonomers and nanoclay particles.

Soft hydrogels with elasticity modulus values lower than 100kPa that are tough and biodegradable are of great interest in medicine and in tissue engineering applications. We have developed a series of soft hydrogel structures from different methacrylate-functionalized triblock copolymers of poly(ethylene glycol) (PEG) with poly(trimethylene carbonate) (PTMC) by photo-crosslinking aqueous solutions of the macromonomers in 2.5 and 5wt.% colloidal dispersions of clay nanoparticles (Laponite XLG). The length of the PTMC blocks of the macromonomers and the clay content determined the physicomechanical properties of the obtained hydrogels. While an increase in the PTMC block length in the macromonomers from 0.2 to 5kg/mol resulted in a decrease in the gel content, the addition of 5wt.% Laponite nanoclay to the crosslinking solution lead to very high gel contents of the hydrogels of more than 95%. The effect of PTMC block length on the mechanical properties of the hydrogels was not as pronounced, and soft gels with a compressive modulus of less than 15kPa and toughness values of 25kJm(-3) were obtained. However, the addition of 5wt.% Laponite nanoclay to the formulations considerably increased the compressive modulus and resilience of the hydrogels; swollen nanocomposite networks with compressive modulus and toughness values of up to 67kPa and 200kJm(-3), respectively, could then be obtained. The prepared hydrogels were shown to be enzymatically degradable by cholesterol esterase and by the action of macrophages. With an increase in PTMC block length in the hydrogels, the rates of mass loss increased, while the incorporated Laponite nanoclay suppressed degradation. Nanocomposite hydrogel structures with a designed gyroid pore network architecture were prepared by stereolithography. Furthermore, in the swollen state the porous gyroid structures were mechanically stable and the pore network remained fully open and interconnected.

Permanent polymer coating for in vivo MRI visualization of tissue reinforcement prostheses.

The clinical advantage of MRI visualization of prostheses in soft tissue prolapses is very appealing as over 1,000000 MRI-transparent synthetic meshes are implanted annually, and postoperative complications such as mesh shrinkage and migration are frequent. Here, the synthesis of a new material composed of a DTPA-Gd complex grafted onto a backbone of PMA via a covalent bond is described (DTPA-Gd-PMA). This new polymer is sprayed onto meshes and gives an MR signal for a long period without any significant release of Gd. In vitro cytocompatibility tests on fibroblasts show limited cytotoxicity. Microscopic investigations indicate that vital cells rapidly colonize the material. Finally, coated meshes implanted in rats are easily recognizable using an MR imaging system.

New magnetic-resonance-imaging-visible poly(ε-caprolactone)-based polyester for biomedical applications.

A great deal of effort has been made since the 1990s to enlarge the field of magnetic resonance imaging. Better tissue contrast, more biocompatible contrast agents and the absence of any radiation for the patient are some of the many advantages of using magnetic resonance imaging (MRI) rather than X-ray technology. But implantable medical devices cannot be visualized by conventional MRI and a tool therefore needs to be developed to rectify this. The synthesis of a new MRI-visible degradable polymer is described by grafting an MR contrast agent (DTPA-Gd) to a non-water-soluble, biocompatible and degradable poly(ε-caprolactone) (PCL). The substitution degree, calculated by (1)H nuclear magnetic resonance and inductively coupled plasma-mass spectrometry, is close to 0.5% and proves to be sufficient to provide a strong and clear T1 contrast enhancement. This new MRI-visible polymer was coated onto a commercial mesh for tissue reinforcement using an airbrush system and enabled in vitro MR visualization of the mesh for at least 1 year. A stability study of the DTPA-Gd-PCL chelate in phosphate-buffered saline showed that a very low amount of gadolinium was released into the medium over 52 weeks, guaranteeing the safety of the device. This study shows that this new MRI-visible polymer has great potential for the MR visualization of implantable medical devices and therefore the post-operative management of patients.