Vascular Tissue Engineering: Challenges and Requirements for an Ideal Large Scale Blood Vessel.

Since the emergence of regenerative medicine and tissue engineering more than half a century ago, one obstacle has persisted: the in vitro creation of large-scale vascular tissue (>1 cm3) to meet the clinical needs of viable tissue grafts but also for biological research applications. Considerable advancements in biofabrication have been made since Weinberg and Bell, in 1986, created the first blood vessel from collagen, endothelial cells, smooth muscle cells and fibroblasts. The synergistic combination of advances in fabrication methods, availability of cell source, biomaterials formulation and vascular tissue development, promises new strategies for the creation of autologous blood vessels, recapitulating biological functions, structural functions, but also the mechanical functions of a native blood vessel. In this review, the main technological advancements in bio-fabrication are discussed with a particular highlights on 3D bioprinting technologies. The choice of the main biomaterials and cell sources, the use of dynamic maturation systems such as bioreactors and the associated clinical trials will be detailed. The remaining challenges in this complex engineering field will finally be discussed.

Monomethyl Auristatin E Grafted-Liposomes to Target Prostate Tumor Cell Lines.

Novel nanomedicines have been engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or short half-life. Lipid-based carriers such as liposomes represent one of the most advanced classes of drug delivery systems. A Monomethyl Auristatin E (MMAE) warhead was grafted on a lipid derivative and integrated in fusogenic liposomes, following the model of antibody drug conjugates. By modulating the liposome composition, we designed a set of particles characterized by different membrane fluidities as a key parameter to obtain selective uptake from fibroblast or prostate tumor cells. Only the fluid liposomes made of palmitoyl-oleoyl-phosphatidylcholine and dioleoyl-phosphatidylethanolamine, integrating the MMAE-lipid derivative, showed an effect on prostate tumor PC-3 and LNCaP cell viability. On the other hand, they exhibited negligible effects on the fibroblast NIH-3T3 cells, which only interacted with rigid liposomes. Therefore, fluid liposomes grafted with MMAE represent an interesting example of drug carriers, as they can be easily engineered to promote liposome fusion with the target membrane and ensure drug selectivity.

Bioinspired Multi-Activities 4D Printing Objects: A New Approach Toward Complex Tissue Engineering.

4D printing is an innovative approach which might in a near future lead to the achievement of highly complex smart materials. The authors describe a new strategy for the achievement of 4D printed objects with multiple biological activities. These activities are generated through the entrapment, during 3D printing, of two distinct enzymes (alkaline phosphatase and thrombin). These two enzymes give then the ability to the 4D printed object to generate bioactivities useful for in vitro tissue engineering. Indeed, it is shown that the entrapped alkaline phosphatase enables the localized and pre-programmed calcification of some 3D object parts while the diffusion of thrombin from the object permits the formation of fibrin biofilm (including living cells) directly at the surface of 3D object. Both activities and enzyme behavior within the 4D printed hydrogel are characterized through enzymatic measurements, microscopy, magnetic resonance imaging (MRI), and cell seeding.