vascularized immunocompetent patient-derived model to test cancer therapies.

This work describes a patient-derived tumoroid model (PDTs) to support precision medicine in lung oncology. The use of human adipose tissue-derived microvasculature and patient-derived peripheral blood mononuclear cells (PBMCs) permits to achieve a physiologically relevant tumor microenvironment. This study involved ten patients at various stages of tumor progression.

Impact of formulation design and lyophilisation on the physicochemical characteristics of finasteride nanosystems.

The fundamental purpose of this study was to develop a stable lyophilised finasteride nanosystem (FNS-NS) for topical delivery. The FNS-NS was fabricated using an ultrasonication technique. The impact of two different cryoprotectants on the physicochemical characteristics of FNS-NS before and after lyophilisation was thoroughly investigated.

Vascularization of Patient-Derived Tumoroid from Non-Small-Cell Lung Cancer and Its Microenvironment.

Patient-derived tumoroid (PDT) has been developed and used for anti-drug screening in the last decade. As compared to other existing drug screening models, a PDT-based in vitro 3D cell culture model could preserve the histological and mutational characteristics of their corresponding tumors and mimic the tumor microenvironment. However, few studies have been carried out to improve the microvascular network connecting the PDT and its surrounding microenvironment, knowing that poor tumor-selective drug transport and delivery is one of the major reasons for both the failure of anti-cancer drug screens and resistance in clinical treatment.

Mechanistic Illustration: How Newly-Formed Blood Vessels Stopped by the Mineral Blocks of Bone Substitutes Can Be Avoided by Using Innovative Combined Therapeutics.

One major limitation for the vascularization of bone substitutes used for filling is the presence of mineral blocks. The newly-formed blood vessels are stopped or have to circumvent the mineral blocks, resulting in inefficient delivery of oxygen and nutrients to the implant. This leads to necrosis within the implant and to poor engraftment of the bone substitute.

Quercetin potentializes the respective cytotoxic activity of gemcitabine or doxorubicin on 3D culture of AsPC-1 or HepG2 cells, through the inhibition of HIF-1α and MDR1.

The impact of cancer on lifespan is significantly increasing worldwide. Enhanced activity of drug efflux pumps and the incidences of the tumor microenvironment such as the apparition of a hypoxic gradient inside of the bulk tumor, are the major causes of chemotherapy failure. For instance, expression of Hypoxia-inducible factor (HIF-1α) has been associated with metastasis, resistance to chemotherapy and reduced survival rate.

Flavagline synthetic derivative induces senescence in glioblastoma cancer cells without being toxic to healthy astrocytes.

Glioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain. It is the most invasive type of glioma developed from astrocytes. Until today, Temozolomide (TMZ) is the only standard chemotherapy for patients with GBM.

Potential Implantable Nanofibrous Biomaterials Combined with Stem Cells for Subchondral Bone Regeneration.

The treatment of osteochondral defects remains a challenge. Four scaffolds were produced using Food and Drug Administration (FDA)-approved polymers to investigate their therapeutic potential for the regeneration of the osteochondral unit. Polycaprolactone (PCL) and poly(vinyl-pyrrolidone) (PVP) scaffolds were made by electrohydrodynamic techniques.

Preclinical safety study of a combined therapeutic bone wound dressing for osteoarticular regeneration.

The extended life expectancy and the raise of accidental trauma call for an increase of osteoarticular surgical procedures. Arthroplasty, the main clinical option to treat osteoarticular lesions, has limitations and drawbacks. In this manuscript, we test the preclinical safety of the innovative implant ARTiCAR for the treatment of osteoarticular lesions.

Pickering nano-emulsion as a nanocarrier for pH-triggered drug release.

This study investigates the formulation of surfactant-free Pickering nano-emulsions able to release a drug at specific pH, in order to enhance its oral bioavailability. The stabilizing nanoparticles composed of magnesium hydroxide, were obtained by nano-precipitation method. The oil-in-water Pickering nano-emulsions stabilized with Mg(OH) nanoparticles, and encapsulating a model of hydrophobic drug (ibuprofen) were formulated following a high-energy process, using a sonication probe.

Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management.

Bone replacement might have been practiced for centuries with various materials of natural origin, but had rarely met success until the late 19th century. Nowadays, many different bone substitutes can be used. They can be either derived from biological products such as demineralized bone matrix, platelet-rich plasma, hydroxyapatite, adjunction of growth factors (like bone morphogenetic protein) or synthetic such as calcium sulfate, tri-calcium phosphate ceramics, bioactive glasses, or polymer-based substitutes.

Maxillary Bone Regeneration Based on Nanoreservoirs Functionalized -Polycaprolactone Biomembranes in a Mouse Model of Jaw Bone Lesion.

Current approaches of regenerative therapies constitute strategies for bone tissue reparation and engineering, especially in the context of genetical diseases with skeletal defects. Bone regeneration using electrospun nanofibers' implant has the following objectives: bone neoformation induction with rapid healing, reduced postoperative complications, and improvement of bone tissue quality. implantation of polycaprolactone (PCL) biomembrane functionalized with BMP-2/Ibuprofen in mouse maxillary defects was followed by bone neoformation kinetics evaluation using microcomputed tomography.

Semaphorin 3A receptor inhibitor as a novel therapeutic to promote innervation of bioengineered teeth.

The sensory innervation of the dental pulp is essential for tooth function and protection. It is mediated by axons originating from the trigeminal ganglia and is spatio-temporally regulated. We have previously shown that the innervation of bioengineered teeth can be achieved only under immunosuppressive conditions.

Temporomandibular Joint Regenerative Medicine.

The temporomandibular joint (TMJ) is an articulation formed between the temporal bone and the mandibular condyle which is commonly affected. These affections are often so painful during fundamental oral activities that patients have lower quality of life. Limitations of therapeutics for severe TMJ diseases have led to increased interest in regenerative strategies combining stem cells, implantable scaffolds and well-targeting bioactive molecules.

Anti-inflammatory effect of active nanofibrous polymeric membrane bearing nanocontainers of atorvastatin complexes.

Aim: We developed polymeric membranes for local administration of nonsoluble anti-inflammatory statin, as potential wound patch in rheumatic joint or periodontal lesions.

Methods: Electrospun polycaprolactone membranes were fitted with polysaccharide-atorvastatin nanoreservoirs by using complexes with poly-aminocyclodextrin. Characterization methods are UV-Visible and X-ray photoelectron spectroscopy, molecular dynamics, scanning and transmission electron microscopy.

Combining 2D angiogenesis and 3D osteosarcoma microtissues to improve vascularization.

Angiogenesis is now well known for being involved in tumor progression, aggressiveness, emergence of metastases, and also resistance to cancer therapies. In this study, to better mimic tumor angiogenesis encountered in vivo, we used 3D culture of osteosarcoma cells (MG-63) that we deposited on 2D endothelial cells (HUVEC) grown in monolayer. We report that endothelial cells combined with tumor cells were able to form a well-organized network, and that tubule-like structures corresponding to new vessels infiltrate tumor spheroids.

Hybrid collagen sponge and stem cells as a new combined scaffold able to induce the re-organization of endothelial cells into clustered networks.

The time needed to obtain functional regenerated bone tissue depends on the existence of a reliable vascular support. Current techniques used in clinic, for example after tooth extraction, do not allow regaining or preserving the same bone volume. Our aim is to develop a cellularized active implant of the third generation, equipped with human mesenchymal stem cells to improve the quality of implant vascularization.

Nanoengineered implant as a new platform for regenerative nanomedicine using 3D well-organized human cell spheroids.

In tissue engineering, it is still rare today to see clinically transferable strategies for tissue-engineered graft production that conclusively offer better tissue regeneration than the already existing technologies, decreased recovery times, and less risk of complications. Here a novel tissue-engineering concept is presented for the production of living bone implants combining 1) a nanofibrous and microporous implant as cell colonization matrix and 2) 3D bone cell spheroids. This combination, double 3D implants, shows clinical relevant thicknesses for the treatment of an early stage of bone lesions before the need of bone substitutes.

Advanced nanostructured medical device combining mesenchymal cells and VEGF nanoparticles for enhanced engineered tissue vascularization.

Aim: Success of functional vascularized tissue repair depends on vascular support system supply and still remains challenging. Our objective was to develop a nanoactive implant enhancing endothelial cell activity, particularly for bone tissue engineering in the regenerative medicine field.

Materials & Methods: We developed a new strategy of tridimensional implant based on cell-dependent sustained release of VEGF nanoparticles.

Slug controls stem/progenitor cell growth dynamics during mammary gland morphogenesis.

Background: Morphogenesis results from the coordination of distinct cell signaling pathways controlling migration, differentiation, apoptosis, and proliferation, along stem/progenitor cell dynamics. To decipher this puzzle, we focused on epithelial-mesenchymal transition (EMT) "master genes". EMT has emerged as a unifying concept, involving cell-cell adhesion, migration and apoptotic pathways.