Microemulsion-Inspired Polysaccharide Nanoparticles for an Advanced Targeted Thrombolytic Treatment.

Among cardiovascular diseases, thrombotic diseases such as ischemic heart disease and acute ischemic strokes are the most lethal, responsible by themselves for a quarter of worldwide deaths. While surgical treatments exist, they may not be used in all situations, and systemic thrombolytic drug injection, such as recombinant tissue plasminogen activators (rtPA), often remains necessary, despite serious limitations including short therapeutic window, severe side effects, and failure to address the complex nature of thrombi. This prompted intense research into alternative thrombolytics or delivery methods, including nanomedicine.

Bone Spheroid Development Under Flow Conditions with Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells in a 3D Porous Hydrogel Supplemented with Hydroxyapatite.

Understanding the niche interactions between blood and bone through the in vitro co-culture of osteo-competent cells and endothelial cells is a key factor in unraveling therapeutic potentials in bone regeneration. This can be additionally supported by employing numerical simulation techniques to assess local physical factors, such as oxygen concentration, and mechanical stimuli, such as shear stress, that can mediate cellular communication. In this study, we developed a Mesenchymal Stem Cell line (MSC) and a Human Umbilical Vein Endothelial Cell line (HUVEC), which were co-cultured under flow conditions in a three-dimensional, porous, natural pullulan/dextran scaffold that was supplemented with hydroxyapatite crystals that allowed for the spontaneous formation of spheroids.

rtPA-loaded fucoidan polymer microbubbles for the targeted treatment of stroke.

Systemic injection of thrombolytic drugs is the gold standard treatment for non-invasive blood clot resolution. The most serious risks associated with the intravenous injection of tissue plasminogen activator-like proteins are the bleeding complication and the dose related neurotoxicity. Indeed, the drug has to be injected in high concentrations due to its short half-life, the presence of its natural blood inhibitor (PAI-1) and the fast hepatic clearance (0.

Bone Regeneration in Small and Large Segmental Bone Defect Models after Radiotherapy Using Injectable Polymer-Based Biodegradable Materials Containing Strontium-Doped Hydroxyapatite Particles.

The reconstruction of bones following tumor excision and radiotherapy remains a challenge. Our previous study, performed using polysaccharide-based microbeads that contain hydroxyapatite, found that these have osteoconductivity and osteoinductive properties. New formulations of composite microbeads containing HA particles doped with strontium (Sr) at 8 or 50% were developed to improve their biological performance and were evaluated in ectopic sites.

Engineered human liver based on pullulan-dextran hydrogel promotes mice survival after liver failure.

Liver tissue engineering approaches aim to support drug testing, assistance devices, or transplantation. However, their suitability for clinical application remains unsatisfactory. Herein, we demonstrate the beneficial and biocompatible use of porous pullulan-dextran hydrogel for the self-assembly of hepatocytes and biliary-like cells into functional 3D microtissues.

Interplay between crosslinking and ice nucleation controls the porous structure of freeze-dried hydrogel scaffolds.

Freeze-drying is a process of choice to texture hydrogel scaffolds with pores formed by an ice-templating mechanism. Using state-of-the-art microscopies (cryo-EBSD, μCT, CLSM), this work evidences and quantifies the effect of crosslinking and ice nucleation temperature on the porous structure of thin hydrogel scaffolds freeze-dried at a low cooling rate. We focused on a polysaccharide-based hydrogel and developed specific protocols to monitor or trigger ice nucleation for this study.

Tuning Physicochemical Properties of a Macroporous Polysaccharide-Based Scaffold for 3D Neuronal Culture.

Central nervous system (CNS) lesions are a leading cause of death and disability worldwide. Three-dimensional neural cultures in biomaterials offer more physiologically relevant models for disease studies, toxicity screenings or in vivo transplantations. Herein, we describe the development and use of pullulan/dextran polysaccharide-based scaffolds for 3D neuronal culture.

Fucoidan-functionalized polysaccharide submicroparticles loaded with alteplase for efficient targeted thrombolytic therapy.

Intravenous administration of fibrinolytic drugs is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and might trigger hemorrhagic transformations. Therefore, it is mandatory to develop innovative nanomedicine-based solutions for more efficient and safer thrombolysis with biocompatible and biodegradable thrombus-targeted nanocarrier.

P-selectin targeting polysaccharide-based nanogels for miRNA delivery.

Nanogels were prepared in aqueous media without the use of any organic solvent via a simple polyelectrolyte complexation method between aminated pullulan and fucoidan followed by covalent crosslinking with genipin. Homogeneously distributed genipin crosslinked nanogels (G-PECs) were obtained with a mean hydrodynamic diameter of ~155 nm and zeta potential of 0.86 ± 4.

Nanostructured lipid carriers accumulate in atherosclerotic plaques of ApoE mice.

Nanostructured lipid carriers (NLC) might represent an interesting approach for the identification and targeting of rupture-prone atherosclerotic plaques. In this study, we evaluated the biodistribution, targeting ability and safety of Cu-fonctionalized NLC in atherosclerotic mice. Cu-chelating-NLC (51.

Erythrocyte-Inspired Discoidal Polymeric Nanoconstructs Carrying Tissue Plasminogen Activator for the Enhanced Lysis of Blood Clots.

Tissue plasminogen activator (tPA) is the sole approved therapeutic molecule for the treatment of acute ischemic stroke. Yet, only a small percentage of patients could benefit from this life-saving treatment because of medical contraindications and severe side effects, including brain hemorrhage, associated with delayed administration. Here, a nano therapeutic agent is realized by directly associating the clinical formulation of tPA to the porous structure of soft discoidal polymeric nanoconstructs (tPA-DPNs).

Influence of the three-dimensional culture of human bone marrow mesenchymal stromal cells within a macroporous polysaccharides scaffold on Pannexin 1 and Pannexin 3.

Because cell interactions play a fundamental role for cell differentiation, we investigated the expression of Pannexin 1 and Pannexin 3 in human bone marrow mesenchymal stromal cells (HBMSCs) in a three-dimensional (3D) microenvironment provided by a polysaccharide-based macroporous scaffold. The pannexin (Panx) family consists of three members, Panx1, Panx2, and Panx3. The roles of Panx large-pore ion and metabolite channels are recognized in many physiological and pathophysiological scenarios, but the role of these proteins in human physiological processes is still under investigation.

In Vitro Mechanical Property Evaluation of Chitosan-Based Hydrogels Intended for Vascular Graft Development.

Vascular grafts made of synthetic polymers perform poorly in cardiac and peripheral bypass applications. In these applications, chitosan-based materials can be produced and shaped to provide a novel scaffold for vascular tissue engineering. The goal of this study was to evaluate in vitro the mechanical properties of a novel chitosan formulation to assess its potential for this scaffold.

Biomimicking polysaccharide nanofibers promote vascular phenotypes: a potential application for vascular tissue engineering.

The potential of electrospun pullulan/dextran (P/D) nanofibers (average diameter = 323 nm) for vascular tissue engineering applications is explored. The mechanical properties of the nanofibers are of the same order of magnitude as that of human arteries (Young's modulus ≈0.88 MPa; tensile strength ≈0.