Murielle Dufresne

Optimizing the fluidized bed bioreactor as an external bioartificial liver

Background Our team previously designed and validated a new bioartificial liver (BAL) called Suppliver based on a Prismaflex™ device, including fluidized bed bioreactors hosting alginate-encapsulated hepatocytes. To ensure correct fluidization within the bioreactor, the beads need to become heavier with the addition of inert glass microspheres. Methods In this study, we assessed the impact of this additional component on the bead production process, bed fluidization, mass transfer and the mechanical properties of the beads, as well as cell viability and basic metabolic function. Results A concentration of 20 mg (1% v/v) of microspheres for 15–20 million cells per milliliter of alginate solution appears to be the best configuration. The filling ratio for the beads in the bioreactors can reach 60%. Four 250-mL bioreactors represent approximately 15% of the hepatocytes in a liver, which is a reasonable target for extracorporeal liver supply. Conclusions Increasing bead density clearly maintained the performances of the fluidized bed with plasma of different compositions, without any risk of release out of the bioreactor. A 1% (v/v)-concentration of microspheres in alginate solution did not result in any alteration of the mechanical or biological behavior. This concentration can thus be applied to the production of large-scale encapsulated biomass for further use of the Suppliver setup in human scale preclinical studies.

Towards the development and characterization of an easy handling sheet-like biohybrid bone substitute.

We designed a sheet-like bone substitute capable of adapting to different geometries and becoming a standard tissue-engineered process for bone surgery. Preosteoblastic cells were seeded on to a monolayer of calcium phosphate granules and cultured in a flat parallelepipedic cell culture chamber for 1 month. From the various diameters of the granules examined, the 80-200 μm group exhibited the most homogeneous performances regarding both biological (cell morphology, viability, differentiation, and simple metabolic activity) and mechanical (cohesion and stress-strain behavior) properties. This sheet was easy to handle after extraction from the culture chamber and showed versatile geometry and flexibility, making it easy to use for surgeons, especially for small defects of the maxillofacial area.

Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and Challenges

Tissue engineering is a promising approach to repair tendon and muscle when natural healing fails. Biohybrid constructs obtained after cells’ seeding and culture in dedicated scaffolds have indeed been considered as relevant tools for mimicking native tissue, leading to a better integration in vivo. They can also be employed to perform advanced in vitro studies to model the cell differentiation or regeneration processes. In this review, we report and analyze the different solutions proposed in literature, for the reconstruction of tendon, muscle, and the myotendinous junction. They classically rely on the three pillars of tissue engineering, i.e., cells, biomaterials and environment (both chemical and physical stimuli). We have chosen to present biomimetic or bioinspired strategies based on understanding of the native tissue structure/functions/properties of the tissue of interest. For each tissue, we sorted the relevant publications according to an increasing degree of complexity in the materials’ shape or manufacture. We present their biological and mechanical performances, observed in vitro and in vivo when available. Although there is no consensus for a gold standard technique to reconstruct these musculo-skeletal tissues, the reader can find different ways to progress in the field and to understand the recent history in the choice of materials, from collagen to polymer-based matrices.

Hepatic cell encapsulation for applications in tissue engineering

Tissue engineering aims at reconstructing tissues based on biomaterials hosting cells reorganised into 3D structure. Alginate is a natural linear polysaccharide with 1.4-linked β-d-mannuronate and ...