Organ‐ and tissue‐level biological functions are intimately linked to microscale cell–cell interactions and to the overarching tissue architecture. Together, biofabrication and organoid technologies offer the unique potential to engineer multi‐scale living constructs, with cellular microenvironments formed by stem cell self‐assembled structures embedded in customizable bioprinted geometries. This study introduces the volumetric bioprinting of complex organoid‐laden constructs, which capture key functions of the human liver. Volumetric bioprinting via optical tomography shapes organoid‐laden gelatin hydrogels into complex centimeter‐scale 3D structures in under 20 s. Optically tuned bioresins enable refractive index matching of specific intracellular structures, countering the disruptive impact of cell‐mediated light scattering on printing resolution. This layerless, nozzle‐free technique poses no harmful mechanical stresses on organoids, resulting in superior viability and morphology preservation post‐printing. Bioprinted organoids undergo hepatocytic differentiation showing albumin synthesis, liver‐specific enzyme activity, and remarkably acquired native‐like polarization. Organoids embedded within low stiffness gelatins (<2 kPa) are bioprinted into mathematically defined lattices with varying degrees of pore network tortuosity, and cultured under perfusion. These structures act as metabolic biofactories in which liver‐specific ammonia detoxification can be enhanced by the architectural profile of the constructs. This technology opens up new possibilities for regenerative medicine and personalized drug testing.
Volumetric Bioprinting
Volumetric bioprinting shapes organoid‐laden constructs into centimeter‐scale assemblies that mimic native liver function. In article number 2110054, Riccardo Levato and co‐workers report the development of a hydrogel‐based bioresin with tunable optical properties to minimize scattering in light‐based printing and ensure high resolution. Organoid viability and maturation is preserved by the shear‐stress‐free printing, and salient liver functions mature in response to the 3D bioprinted architecture.
Recently, the copper toxicosis (CT) locus in Bedlington terriers was assigned to canine chromosome region CFA10q26, which is homologous to human chromosome region HSA2p13-21. A comparative map between CFA10q21-26 and HSA2p13-21 was constructed by using genes already localized to HSA2p13-21. A high-resolution radiation map of CFA10q21-26 was constructed to facilitate positional cloning of the CT gene. For this map, seven Type I and eleven Type II markers were mapped. Using homozygosity mapping, the CT locus could be confined to a 42.3 cR(3000) region, between the FH2523 and C10.602 markers. On the basis of a partial BAC contig, it was estimated that 1-cR(3000) is equivalent to approximately 210 kb, implying that the CT candidate region is therefore estimated to be about 9 Mb.
Summary
Many inherited diseases occur in pure‐bred dogs, but diagnosis at the level of DNA is impossible because the canine genome is largely unknown. Random amplification of polymorphic DNA (RAPD) provides many polymorphisms, but the reproducibility and Mendelian inheritance are not beyond doubt. An optimized polymerase chain reaction (PCR) was developed for canine DNA with respect to the annealing temperature and the concentrations of MgCl2, template DNA and primers. RAPD amplification products were in the range of 100–1500 base pairs. With six primers, 21 different reactions with different electrophoretic patterns were obtained, yielding 9–29 products per reaction. In DNA from dogs of 16 different breeds, 14% of the products were polymorphic; when only beagles were included the rate of polymorphism was 10%. All of the reaction products were completely reproducible in 16 DNA samples. Mendelian transmission was analysed in six beagle families (42 dogs). The segregation of polymorphic amplification products in 21 reactions performed on DNA from all beagles was nearly complete; in only two of the 630 reactions was there a product that could not be traced back to either of the parents. The reproducibility and Mendelian behaviour of polymorphisms generated by RAPD in dogs makes this tool very suitable for development of DNA markers of canine inherited diseases.
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