Advanced bioengineering technologies for preclinical research

Figures & data

Figure 1. Optic-cup-like organoid formed spontaneously from the 3D culture of mouse embryonic stem cell aggregates in the presence of matrigel. Reprinted from reference [15] with permission. (a-l) show the temporal progression of the optic-cup-like structure formation along with the expression of key molecular markers for specific stages in the process. (m) shows the optic cup in a mouse embryo at time E11.5. (n) shows a schematic representation of key stages in the maturation of optic-cup-like. Copyright Nature Publishing Group (2011).

Figure 2. (a) Micropatterned co-cultures (MPCC) with fibroblasts are employed to enhance the maturity of human hepatocytes derived from iPSCs. Reprinted from reference [36] with permission. (b) Cardiac microtissues casted on silicone posts: fabrication process and generation of large microtissue arrays. Cross-sectional view of a single microtissue (scale bars: 800 μm (array), 100 μm (cross section)‏. Reprinted from reference [41] with permission. (c) Biowire fabrication set-up: a suspension of cardiomyocytes in collagen type I gel is seeded in a PDMS channel around a suture wire. The wires can be easily incorporate in an electrostimulation chamber. Images of the biowire formed at low magnification and after Hematoxylin and Eosin (H&E) staining. Reprinted from reference [44] with permission. (d) Schematic representation of skin reconstruction in vitro. Histological sections of normal human skin and reconstructed skin a day 7 of air exposed culture conditions. Reprinted from reference [49] with permission.

Figure 3. (a) Recapitulation of tissue fibrogenesis in lung microtissues. TGF-β1 treatment induced strong expressions fibrosis biomarkers (α-SMA stress fibers, cytosolic pro-collagen, and EDA-Fibronectin (Fn)), while SEM images of a time-lapse microscopy showed elevated contraction of the fibrotic tissue (scale bar: 200 µm). Reprinted from reference [52] with permission (http://creativecommons.org/licenses/by/4.0/) (b) Cardiac microtissues assembled on fiber matrices from healthy and MYBPC3 deficient cells (scale bar: 50 µm). Confocal images showed no structural disarray but calcium dynamics showed clear abnormalities. Reprinted from reference [53] with permission. (c) Lung tissue models to evaluate the severity of the damaged produced by several strains of Staphylococcus aureus found in patients with pneumonia. Reprinted from reference [58] with permission (http://creativecommons.org/licenses/by/4.0/).

Figure 4. (a) Schematic of the process to produce cell-laden hydrogels with perfusable vascular networks using sacrificial glass fibers. (b) Cross-section of the construct showing vascular network lined with endothelial cells, vessel sprouts and intervessel junctions. Reprinted from reference [75] with permission. Copyright Nature Publishing Group (2012).

Figure 5. (a) Placenta-on-a-chip, consisting of two microchannels separated by a semipermeable membrane sandwiched between a trophoblast and an endothelial cell monolayer, mimicking the maternal-fetal interface. (b) Three-dimensional rendering (top) and cross-sectional view (bottom) of the bioengineered placental barrier consisting of trophoblast cells cultured on the apical side of the membrane and villous endothelial cells adhering on the basal side of the membrane. Scale bar: 30 μm. Reprinted from reference [81] with permission. Copyright Royal Society of Chemistry (2017). (c) Schematic of a lung-on-a-chip, consisting of an epithelial and endothelial cell monolayer separated by a porous membrane to recapitulate the alveolar-capillary barrier of human lungs. In order to include biomechanical cues, a vacuum was applied to mimic the stretching of the tissue during breathing. The lung-on-a-chip permitted to reconstitute organ-level functions such as (d) the immune response to bacteria and (e) pulmonary edema. Reprinted from reference [89] with permission. Copyright Nature Publishing Group (2015).

Figure 6. (a) Fabrication of patterned PDMS substrates to mimic the epidermal rete ridges. Keratinocyte patterning on collage-coated PDMS substrates (involucrin stained in yellow, β1 integrin stained in red, scale bar: 200 µm). Reprinted from reference [100] with permission. (b) Hair follicles formed on microwells of collagen gels laden with dermal fibroblasts (FB). First, dermal papilla cells (DPC) were seeded within the wells, and then keratinocytes (KC). Cross sections of the construct (scale bar 2 mm) and immunostaining (scale bar 100 µm) show active DPC cells at their physiological positions (black arrows). Prolonged culture period led to hair fiber formation (arrowheads, scale bar 2 mm). Reprinted from reference [48] with permission (http://creativecommons.org/licenses/by/4.0/). (c) Intestinal villi-like microstructures fabricated by dynamic photopolymerization on poly(ethylene glycol) hydrogels provide the barrier formed CaCo-2 cells with improved physiological characteristics (scale bars: 150 µm; (upper row); 200 µm (lower row, left and middle); 50 µm (lower row, right)). Reprinted from reference [106] with permission.

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