A critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from human induced pluripotent stem cells (iPSCs). Despite many reports describing functional cell differentiation, no studies have succeeded in generating a three-dimensional vascularized organ such as liver. Here we show the generation of vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro (iPSC-LBs). Specified hepatic cells (immature endodermal cells destined to track the hepatic cell fate) self-organized into three-dimensional iPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells. Immunostaining and gene-expression analyses revealed a resemblance between in vitro grown iPSC-LBs and in vivo liver buds. Human vasculatures in iPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of iPSC-LBs into tissue resembling the adult liver. Highly metabolic iPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement. Furthermore, mesenteric transplantation of iPSC-LBs rescued the drug-induced lethal liver failure model. To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells. Although efforts must ensue to translate these techniques to treatments for patients, this proof-of-concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine.

The effect of the addition of graphene on the glass transition temperature (T g) of polymers was investigated, first with poly­(methyl methacrylate) and then with an extensive literature review. Isotactic (i-PMMA) and atactic PMMA (a-PMMA) were blended with pristine graphene (PG) and thermally reduced graphene (TRG). A T g increase was found for a-PMMA nanocomposites made via in situ polymerization with TRG but not when a-PMMA was solvent blended with TRG. However, a T g increase was found for TRG solvent blended into i-PMMA and a smaller increase for PG with i-PMMA. Nearly all the increase occurred at the lowest loading, 0.25 wt %, with little change at increased graphene concentration. T g increases due to interfacial interactions between matrix polymers and fillers. Physical blending such as solvent processes cannot provide enough interaction at the interfaces, whereas chemical blending processes such as in situ polymerization can yield strong covalent bonds. However, i-PMMA molecules can align on graphene sheets at the interface, creating more interaction between i-PMMA and graphene than a-PMMA. Also, the T g of i-PMMA is 60 °C lower than a-PMMA, meaning that hydrogen bonds are stronger at the lower temperature. The T g increase of TRG/i-PMMA is higher than that of PG/i-PMMA due to more oxygen functionalities on TRG than on PG to act as interfacial interaction sites. A broad literature survey agrees with our PMMA results. We found no changes in T g for graphene/polymer nanocomposites synthesized via physical blending processes such as solvent or melt blending, except for blending with strongly polar polymers. In contrast, chemical blending processes such as in situ polymerization or chemically modified fillers yielded significant T g increases in graphene/polymer nanocomposites.

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Graphene was modified with trimellitic anhydride groups, and its polyethylene-terephthalate-based (PET-based) nanocomposites were prepared by melt-mixing. Percolation thresholds observed from changes to the electrical conductivity and storage moduli of nanocomposite melts suggest that the dispersion levels of unmodified graphene and those of modified graphene in PET matrix were the same. An enhancement of G′ and unexpectedly higher [η] for modified graphene at low concentration suggest that PET chains were grafted on the graphene surface creating a coupled network via covalent bonding. The bulk mechanical properties of amorphous nanocomposites were evaluated by tensile-testing. The nanocomposites with modified graphene also displayed an enhanced Young's modulus as well as higher elongation compared to nanocomposites prepared with unmodified graphene. Differential scanning calorimetry, Fourier-transform infrared spectroscopy, and Raman spectroscopy results obtained on stretched nanocomposites suggest that both strain-induced orientation and strain-induced crystallization were suppressed by the modified graphene.