Gelatin-Based Hybrid Hydrogels as Matrices for Organoid Culture.

The application of liver organoids is very promising in the field of liver tissue engineering; however, it is still facing some limitations. One of the current major limitations is the matrix in which they are cultured. The mainly undefined and murine-originated tumor matrices derived from Engelbreth-Holm-Swarm (EHS) sarcoma, such as Matrigel, are still the standard culturing matrices for expansion and differentiation of organoids toward hepatocyte-like cells, which will obstruct its future clinical application potential. In this study, we exploited the use of newly developed highly defined hydrogels as potential matrices for the culture of liver organoids and compared them to Matrigel and two hydrogels that were already researched in the field of organoid research [i.e., polyisocyanopeptides, enriched with laminin-entactin complex (PIC-LEC) and gelatin methacryloyl (GelMA)]. The newly developed hydrogels are materials that have a physicochemical resemblance with native liver tissue. Norbornene-modified dextran cross-linked with thiolated gelatin (DexNB-GelSH) has a swelling ratio and macro- and microscale properties that highly mimic liver tissue. Norbornene-modified chondroitin sulfate cross-linked with thiolated gelatin (CSNB-GelSH) contains chondroitin sulfate, which is a glycosaminoglycan (GAG) that is present in the liver ECM. Furthermore, CSNB-GelSH hydrogels with different mechanical properties were evaluated. Bipotent intrahepatic cholangiocyte organoids (ICOs) were applied in this work and encapsulated in these materials. This research revealed that the newly developed materials outperformed Matrigel, PIC-LEC, and GelMA in the differentiation of ICOs toward hepatocyte-like cells. Furthermore, some trends indicate that an interplay of both the chemical composition and the mechanical properties has an influence on the relative expression of certain hepatocyte markers. Both DexNB-GelSH and CSNB-GelSH showed promising results for the expansion and differentiation of intrahepatic cholangiocyte organoids. The stiffest CSNB-GelSH hydrogel even significantly outperformed Matrigel based on ALB, BSEP, and CYP3A4 gene expression, being three important hepatocyte markers.

Single-particle electrophoresis for studying the adsorption of cationic polymers onto anionic particles.

Understanding the adsorption of polymers onto particles is crucial for many technological and biomedical applications. Even though polymer adsorption on particles is a dynamic process, most experimental techniques can only study the adsorption indirectly, in equilibrium and on the ensemble level. New analysis methods are required to overcome these limitations. We investigated the use of single-particle electrophoresis to study the adsorption kinetics of cationic polymers onto anionic particles and compared the resulting data to a theoretical model. In this approach, the electrophoretic mobility of single polystyrene (PS) particles, exposed to different concentrations of poly(2-guanidinoethyl methacrylate), was measured as a function of time. The polymer adsorption leads to an electrophoretic mobility change of the PS particle over time, from the initial negative value to a positive value at equilibrium. By fitting the kinetics data to the Langmuir model, the adsorption rate, desorption rate and equilibrium constant were determined. Finally, the adsorption kinetics of several other polymers was investigated. This showed that the presented technique enables direct analysis and comparison of the kinetics of polymer adsorption on the single-particle level.

Gelatin-Based Hybrid Hydrogel Scaffolds: Toward Physicochemical Liver Mimicry.

There exists a clear need to develop novel materials that could serve liver tissue engineering purposes. Those materials need to be researched for the development of bioengineered liver tissue as an alternative to donor livers, as well as for materials that could be applied for scaffolds to develop an in vitro model for drug-induced liver injury (DILI) detection . In this paper, the hydrogels oxidized dextran-gelatin (Dexox-Gel) and norbornene-modified dextran-thiolated gelatin (DexNB-GelSH) were developed, and their feasibility toward processing via indirect 3D-printing was investigated with the aim to develop hydrogel scaffolds that physicochemically mimic native liver tissue. Furthermore, their in vitro biocompatibility was assessed using preliminary biological tests using HepG2 cells. Both materials were thoroughly physicochemically characterized and benchmarked to the methacrylated gelatin (GelMA) reference material. Due to inferior properties, Dexox-gel was not further processed into 3D-hydrogel scaffolds. This research revealed that DexNB-GelSH exhibited physicochemical properties that were in excellent agreement with the properties of natural liver tissue in contrast to GelMA. In combination with an equally good biological evaluation of DexNB-GelSH in comparison with GelMA based on an MTS proliferation assay and an albumin quantification assay, DexNB-GelSH can be considered promising in the field of liver tissue engineering.

Solid-State Crosslinkable, Shape-Memory Polyesters Serving Tissue Engineering.

Acrylate-endcapped urethane-based precursors constituting a poly(D,L-lactide)/poly(ε-caprolactone) (PDLLA/PCL) random copolymer backbone are synthesized with linear and star-shaped architectures and various molar masses. It is shown that the glass transition and thus the actuation temperature could be tuned by varying the monomer content (0-8 wt% ε-caprolactone, Tg,crosslinked = 10-42 °C) in the polymers. The resulting polymers are analyzed for their physico-chemical properties and viscoelastic behavior (G'max = 9.6-750 kPa). The obtained polymers are subsequently crosslinked and their shape-memory properties are found to be excellent (Rr = 88-100%, Rf = 78-99.5%). Moreover, their potential toward processing via various additive manufacturing techniques (digital light processing, two-photon polymerization and direct powder extrusion) is evidenced with retention of their shape-memory effect. Additionally, all polymers are found to be biocompatible in direct contact in vitro cell assays using primary human foreskin fibroblasts (HFFs) through MTS assay (up to ≈100% metabolic activity relative to TCP) and live/dead staining (>70% viability).

Tubular Bioartificial Organs: From Physiological Requirements to Fabrication Processes and Resulting Properties. A Critical Review.

In this featured review manuscript, the aim is to present a critical survey on the processes available for fabricating bioartificial organs (BAOs). The focus will be on hollow tubular organs for the transport of anabolites and catabolites, i.e., vessels, trachea, esophagus, ureter and urethra, and intestine. First, the anatomic hierarchical structures of tubular organs, as well as their principal physiological functions, will be presented, as this constitutes the mandatory requirements for effectively designing and developing physiologically relevant BAOs. Second, 3D bioprinting, solution electrospinning, and melt electrowriting will be introduced, together with their capacity to match the requirements imposed by designing scaffolds compatible with the anatomical and physiologically relevant environment. Finally, the intrinsic correlation between processes, materials, and cells will be critically discussed, and directives defining the strengths, weaknesses, and opportunities offered by each process will be proposed for assisting bioengineers in the selection of the appropriate process for the target BAO and its specific required functions.

Bio-Nanohybrid Gelatin/Quantum Dots for Cellular Imaging and Biosensing Applications.

The bio-nanohybrid gelatin protein/cadmium sulfide (Gel/CdS) quantum dots (QDs) have been designed via a facile one-pot strategy. The amino acids group of gelatin chelate Cd2+ and grow CdS QDs without any agglomeration. The 1H NMR spectra indicate that during the above process there are no alterations of the gelatin protein structure conformation and chemical functionalities. The prepared Gel/CdS QDs were characterized and their potential as a system for cellular imaging and the electrochemical sensor for hydrogen peroxide (H2O2) detection applications were investigated. The obtained results demonstrate that the developed Gel/CdS QDs system could offer a simple and convenient operating strategy both for the class of contrast agents for cell labeling and electrochemical sensors purposes.

Increasing the Microfabrication Performance of Synthetic Hydrogel Precursors through Molecular Design.

Implementation of hydrogel precursors in two-photon polymerization (2PP) technology provides promising opportunities in the tissue engineering field thanks to their soft characteristics and similarity to extracellular matrix. Most of the hydrogels, however, are prone to post-fabrication deformations, leading to a mismatch between the computer-aided design and the printed structure. In the present work, we have developed novel synthetic hydrogel precursors to overcome the limitations associated with 2PP processing of conventional hydrogel precursors such as post-processing deformations and a narrow processing window. The precursors are based on a poly(ethylene glycol) backbone containing urethane linkers and are, on average, functionalized with six acrylate terminal groups (three on each terminal group). As a benchmark material, we exploited a precursor with an identical backbone and urethane linkers, albeit functionalized with two acrylate groups, that were reported as state-of-the-art. An in-depth characterization of the hexafunctional precursors revealed a reduced swelling ratio (<0.7) and higher stiffness (>36 MPa Young's modulus) compared to their difunctional analogs. The superior physical properties of the newly developed hydrogels lead to 2PP-based fabrication of stable microstructures with excellent shape fidelity at laser scanning speeds up to at least 90 mm s-1, in contrast with the distorted structures of conventional difunctional precursors. The hydrogel films and microscaffolds revealed a good cell interactivity after functionalization of their surface with a gelatin methacrylamide-based coating. The proposed synthesis strategy provides a one-pot and scalable synthesis of hydrogel building blocks that can overcome the current limitations associated with 2PP fabrication of hydrogel microstructures.

High-Resolution 3D Bioprinting of Photo-Cross-linkable Recombinant Collagen to Serve Tissue Engineering Applications.

Various biopolymers, including gelatin, have already been applied to serve a plethora of tissue engineering purposes. However, substantial concerns have arisen related to the safety and the reproducibility of these materials due to their animal origin and the risk associated with pathogen transmission as well as batch-to-batch variations. Therefore, researchers have been focusing their attention toward recombinant materials that can be produced in a laboratory with full reproducibility and can be designed according to specific needs (e.g., by introducing additional RGD sequences). In the present study, a recombinant protein based on collagen type I (RCPhC1) was functionalized with photo-cross-linkable methacrylamide (RCPhC1-MA), norbornene (RCPhC1-NB), or thiol (RCPhC1-SH) functionalities to enable high-resolution 3D printing via two-photon polymerization (2PP). The results indicated a clear difference in 2PP processing capabilities between the chain-growth-polymerized RCPhC1-MA and the step-growth-polymerized RCPhC1-NB/SH. More specifically, reduced swelling-related deformations resulting in a superior CAD-CAM mimicry were obtained for the RCPhC1-NB/SH hydrogels. In addition, RCPhC1-NB/SH allowed the processing of the material in the presence of adipose tissue-derived stem cells that survived the encapsulation process and also were able to proliferate when embedded in the printed structures. As a consequence, it is the first time that successful HD bioprinting with cell encapsulation is reported for recombinant hydrogel bioinks. Therefore, these results can be a stepping stone toward various tissue engineering applications.

Bioprinting predifferentiated adipose-derived mesenchymal stem cell spheroids with methacrylated gelatin ink for adipose tissue engineering.

The increasing number of mastectomies results in a greater demand for breast reconstruction characterized by simplicity and a low complication profile. Reconstructive surgeons are investigating tissue engineering (TE) strategies to overcome the current surgical drawbacks. 3D bioprinting is the rising technique for the fabrication of large tissue constructs which provides a potential solution for unmet clinical needs in breast reconstruction building on decades of experience in autologous fat grafting, adipose-derived mesenchymal stem cell (ASC) biology and TE. A scaffold was bioprinted using encapsulated ASC spheroids in methacrylated gelatin ink (GelMA). Uniform ASC spheroids with an ideal geometry and diameter for bioprinting were formed, using a high-throughput non-adhesive agarose microwell system. ASC spheroids in adipogenic differentiation medium (ADM) were evaluated through live/dead staining, histology (HE, Oil Red O), TEM and RT-qPCR. Viable spheroids were obtained for up to 14 days post-printing and showed multilocular microvacuoles and successful differentiation toward mature adipocytes shown by gene expression analysis. Moreover, spheroids were able to assemble at random in GelMA, creating a macrotissue. Combining the advantage of microtissues to self-assemble and the controlled organization by bioprinting technologies, these ASC spheroids can be useful as building blocks for the engineering of soft tissue implants.

Technological advancements for the development of stem cell-based models for hepatotoxicity testing.

Stem cells are characterized by their self-renewal capacity and their ability to differentiate into multiple cell types of the human body. Using directed differentiation strategies, stem cells can now be converted into hepatocyte-like cells (HLCs) and therefore, represent a unique cell source for toxicological applications in vitro. However, the acquired hepatic functionality of stem cell-derived HLCs is still significantly inferior to primary human hepatocytes. One of the main reasons for this is that most in vitro models use traditional two-dimensional (2D) setups where the flat substrata cannot properly mimic the physiology of the human liver. Therefore, 2D-setups are progressively being replaced by more advanced culture systems, which attempt to replicate the natural liver microenvironment, in which stem cells can better differentiate towards HLCs. This review highlights the most recent cell culture systems, including scaffold-free and scaffold-based three-dimensional (3D) technologies and microfluidics that can be employed for culture and hepatic differentiation of stem cells intended for hepatotoxicity testing. These methodologies have shown to improve in vitro liver cell functionality according to the in vivo liver physiology and allow to establish stem cell-based hepatic in vitro platforms for the accurate evaluation of xenobiotics.

Highly Reactive Thiol-Norbornene Photo-Click Hydrogels: Toward Improved Processability.

In the present work, gelatin type B is modified with highly reactive norbornene functionalities (Gel-NB) following a one-pot synthesis approach to enable subsequent thiol-ene photo-click crosslinking. The modification strategy displays close control over the amount of introduced functionalities. Additionally, Gel-NB exhibits considerably improved processing capabilities in terms of two-photon polymerization when benchmarked to earlier-reported crosslinkable gelatin derivatives (e.g., gelatin-methacrylamide (Gel-MOD) and gelatin-methacrylamide-aminoethylmethacrylate (Gel-MOD-AEMA)). The improvement is especially apparent in terms of minimally required laser power (20 mW vs ≥60 mW (Gel-MOD) vs ≥40 mW (Gel-MOD-AEMA) at 100 mm s-1 scan speed) and processable concentration range (≥5 w/v% vs ≥10 w/v% (Gel-MOD/Gel-MOD-AEMA)). Furthermore, the proposed functionalization scheme maintains the excellent biocompatibility and cell interactivity of gelatin. Additionally, the norbornene functionalities have potential for straightforward postprocessing "thiol-ene" surface grafting of active molecules. As a consequence, a very promising material toward tissue engineering applications and more specifically, biofabrication, is presented.

Joint academic and industrial efforts towards innovative and efficient solutions for clinical needs.

The 4th Translational Research Symposium (TRS) was organised at the annual meeting of the European Society for Biomaterials (ESB) 2017, Athens, Greece, with a focus on 'Academia-Industry Clusters of Research for Innovation Catalysis'. Collaborations between research institutes and industry can be sustained in several ways such as: European Union (EU) funded consortiums; syndicates of academic institutes, clinicians and industries; funding from national governments; and private collaborations between universities and companies. Invited speakers from industry and research institutions presented examples of these collaborations in the translation of research ideas or concepts into marketable products. The aim of the present article is to summarize the key messages conveyed during these lectures. In particular, emphasis is put on the challenges to appropriately identify and select unmet clinical needs and their translation by ultimately implementing innovative and efficient solutions achieved through joint academic and industrial efforts.

Cross-Linkable Gelatins with Superior Mechanical Properties Through Carboxylic Acid Modification: Increasing the Two-Photon Polymerization Potential.

The present work reports on the development of photo-cross-linkable gelatins sufficiently versatile to overcome current biopolymer two-photon polymerization (2PP) processing limitations. To this end, both the primary amines as well as the carboxylic acids of gelatin type B were functionalized with photo-cross-linkable moieties (up to 1 mmol/g) resulting in superior and tunable mechanical properties (G' from 5000 to 147000 Pa) enabling efficient 2PP processing. The materials were characterized in depth prior to and after photoinduced cross-linking using fully functionalized gelatin-methacrylamide (gel-MOD) as a benchmark to assess the effect of functionalization on the protein properties, cross-linking efficiency, and mechanical properties. In addition, preliminary experiments on hydrogel films indicated excellent in vitro biocompatibility (close to 100% viability) both in the presence of MC3T3 preosteoblasts and L929 fibroblasts. Moreover, 2PP processing of the novel derivative was superior in terms of applied laser power (≥40 vs ≥60 mW for gel-MOD at 100 mm/s) as well as post-production swelling (0-20% vs 75-100% for gel-MOD) compared to those of gel-MOD. The reported novel gelatin derivative (gel-MOD-AEMA) proves to be extremely suitable for direct laser writing as both superior mimicry of the applied computer-aided design (CAD) was obtained while maintaining the desired cellular interactivity of the biopolymer. It can be anticipated that the present work will also be applicable to alternative biopolymers mimicking the extracellular environment such as collagen, elastin, and glycosaminoglycans, thereby expanding current material-related processing limitations in the tissue engineering field.

Intravenous and intratumoral injection of Pluronic P94: The effect of administration route on biodistribution and tumor retention.

Pluronics P94 are block-copolymer showing prolonged circulation time and tumor-cell internalization in vitro, suggesting a potential for tumor accumulation and as a drug carrier. Here we report the results of the radiolabeled-P94 unimers (P94-111In-DTPA) on tumor uptake/retention and biodistribution after intravenous and intratumoral injection to tumor-bearing mice. Intravenous administration results in a high radioactive signal in the liver; while in tumor and other healthy tissues only low levels of radioactivity could be measured. In contrast, the intratumoral injection of P94 resulted in elevated levels of radioactivity in the tumor and low levels in other organs, including the liver. Independently from the injection route, the tumor tissue presented long retention of radioactivity. The minimal involvement of off-target tissues of P94, together with the excellent tracer retention over-time in the tumor designates Pluronic P94 copolymer as a highly promising carrier for anti-tumor drugs.

Cell response of flexible PMMA-derivatives: supremacy of surface chemistry over substrate stiffness.

The present work reports on the development of a range of poly(methyl methacrylate)/poly(ethylene glycol) (PMMAPEG)-based materials, characterized by different elasticity moduli in order to study the influence of the substrate's mechanical properties on the response of human umbilical vein endothelial cells (HUVECs). To render the selected materials cell-interactive, a polydopamine (PDA)/gelatin type B (Gel B) coating was applied. Prior to the in vitro assay, the success of the PDA and Gel B immobilization onto the materials was confirmed using X-ray photoelectron spectroscopy (XPS) as reflected by the nitrogen percentages measured for the materials after PDA and Gel B deposition. Tensile tests showed that materials with E-moduli ranging from 37 to 1542 MPa could be obtained by varying the ratio between PMMA and PEG as well as the PEG molecular weight and its functionality (i.e. mono-methacrylate vs. di-methacrylate). The results after 1 day of cell contact suggested a preferred HUVECs cell growth onto more rigid materials. After 1 week, the material with the lowest E-modulus of 37 MPa showed lower cell densities compared to the other materials. No clear correlation could be observed between the number of focal adhesion points and the substrate stiffness. Although minor differences were found, these were not statistically significant. This last conclusion again highlights the universal character of the PDA/Gel B modification. The present work could thus be valuable for the development of a range of cell substrates requiring different mechanical properties in line with the envisaged application while the cell response should ideally remain unaffected.

SPECT/CT Imaging of Pluronic Nanocarriers with Varying Poly(ethylene oxide) Block Length and Aggregation State.

Optimal biodistribution and prolonged circulation of nanocarriers improve diagnostic and therapeutic effects of enhanced permeability and retention-based nanomedicines. Despite extensive use of Pluronics in polymer-based pharmaceuticals, the influence of different poly(ethylene oxide) (PEO) block length and aggregation state on the biodistribution of the carriers is rather unexplored. In this work, we studied these effects by evaluating the biodistribution of Pluronic unimers and cross-linked micelles with different PEO block size. In vivo biodistribution of (111)In-radiolabeled Pluronic nanocarriers was investigated in healthy mice using single photon emission computed tomography. All carriers show fast uptake in the organs from the reticuloendothelial system followed by a steady elimination through the hepatobiliary tract and renal filtration. The PEO block length affects the initial renal clearance of the compounds and the overall liver uptake. The aggregation state influences the long-term accumulation of the nanocarriers in the liver. We showed that the circulation time and elimination pathways can be tuned by varying the physicochemical properties of Pluronic copolymers. Our results can be beneficial for the design of future Pluronic-based nanomedicines.

Polydopamine-Gelatin as Universal Cell-Interactive Coating for Methacrylate-Based Medical Device Packaging Materials: When Surface Chemistry Overrules Substrate Bulk Properties.

Despite its widespread application in the fields of ophthalmology, orthopedics, and dentistry and the stringent need for polymer packagings that induce in vivo tissue integration, the full potential of poly(methyl methacrylate) (PMMA) and its derivatives as medical device packaging material has not been explored yet. We therefore elaborated on the development of a universal coating for methacrylate-based materials that ideally should reveal cell-interactivity irrespective of the polymer substrate bulk properties. Within this perspective, the present work reports on the UV-induced synthesis of PMMA and its more flexible poly(ethylene glycol) (PEG)-based derivative (PMMAPEG) and its subsequent surface decoration using polydopamine (PDA) as well as PDA combined with gelatin B (Gel B). Successful application of both layers was confirmed by multiple surface characterization techniques. The cell interactivity of the materials was studied by performing live-dead assays and immunostainings of the cytoskeletal components of fibroblasts. It can be concluded that only the combination of PDA and Gel B yields materials possessing similar cell interactivities, irrespective of the physicochemical properties of the underlying substrate. The proposed coating outperforms both the PDA functionalized and the pristine polymer surfaces. A universal cell-interactive coating for methacrylate-based medical device packaging materials has thus been realized.

Di-Calcium Phosphate and Phytosphingosine as an Innovative Acid-Resistant Treatment to Occlude Dentine Tubules.

The present investigation evaluated the ability of an experimental di-calcium phosphate (DCP) desensitising agent used alone or combined with phytosphingosine (PHS) to occlude dentine tubules and resist a citric acid (CA) or artificial saliva (AS) challenge. Three groups of human dentine specimens (DS) were treated with the following: (1) PHS alone, (2) DCP or (3) a combination of PHS and DCP. Dentine hydraulic conductance of DS was evaluated using a digital flow sensor at 6.9 kPa. The average fluid volume for each of the treated DS was used to calculate the total dentine permeability reduction (%P) prior to and following CA immersion for 1 min or AS immersion for 4 weeks. The treated DS were subjected to both scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy analysis. Statistically significant differences (%P) were identified between the groups by ANOVA and Fisher's multiple comparison test (p < 0.05), respectively. Interestingly, both PHS and DCP appeared to work synergistically. DS treated with DCP or PHS/DCP demonstrated a significant reduction (%P) prior to and following CA or AS challenge (p < 0.05). Both the SEM and FTIR analyses showed consistent brushite crystals occluding the dentine tubules. Conversely, the application of PHS alone failed to demonstrate any significant reduction of dentine permeability (p > 0.05) or show any evidence of occlusion of the dentine tubules. DCP can be used alone or combined with PHS to decrease the dentine permeability as well as to resist a CA and AS challenge. These results would, therefore, suggest that DCP may be a suitable treatment option for dentine hypersensitivity.

Photo-crosslinkable biopolymers targeting stem cell adhesion and proliferation: the case study of gelatin and starch-based IPNs.

The present work focuses on the development of biomaterials that support the adhesion and the proliferation of adipose-tissue derived stem cells. Therefore, gelatin and starch are selected as starting materials. Both hydrogel building blocks are of great interest as they provide a general chemical structure comparable to the protein and the polysaccharide constituting part of the extracellular matrix. Crosslinkable side groups are incorporated on both biopolymers to enable the subsequent chemical crosslinking, thereby ensuring their stability at physiological temperature. An in vitro cellular assay revealed that the hydrogels developed are biocompatible and supported cell adhesion of adipose-tissue derived mesenchymal stem cells. The presence of the starch phase tempered the adhesion resulting in local cell detachment. The results thus indicate that by carefully varying the ratio of the two building blocks, hydrogels can be developed possessing a controllable cell adhesion behavior.

An electro-responsive hydrogel for intravascular applications: an in vitro and in vivo evaluation.

There is a growing interest in using hydrogels for biomedical applications, because of more favourable characteristics. Some of these hydrogels can be activated by using particular stimuli, for example electrical fields. These stimuli can change the hydrogel shape in a predefined way. It could make them capable of adaptation to patient-specific anatomy even post-implantation. This is the first paper aiming to describe in vivo studies of an electro-responsive, Pluronic F127 based hydrogel, for intravascular applications. Pluronic methacrylic acid hydrogel (PF127/MANa) was in vitro tested for its haemolytic and cytotoxic effects. Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation. Indirect and direct testing of the material gave no indication of the haemolytic effects of the material. Determination of fibroblast viability after 24 h of incubation in an extract of the hydrogel showed no cytotoxic effects. Occlusion was obtained within 1 h following in vivo implantation. Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall. An important proof-of-concept was obtained showing biocompatibility and effectiveness of a pluronic based electro-responsive hydrogel for obtaining an arterial occlusion with limited biological impact. So the selected pluronic-methacrylic acid based hydrogel can be used as an endovascular occlusion device. More importantly it is the first step in further development of electro-active hydrogels for a broad range of intra-vascular applications (e.g. system to prevent endoleakage in aortic aneurysm treatment, intra-vascular drug delivery).