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Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment1,2. However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates3. In this study, we generated islets from human chemically induced pluripotent stem cells (hCiPSC-islets) and show that a one-dose intraportal infusion of hCiPSC-islets into diabetic non-human primates effectively restored endogenous insulin secretion and improved glycemic control. Fasting and average pre-prandial blood glucose levels significantly decreased in all recipients, accompanied by meal or glucose-responsive C-peptide release and overall increase in body weight. Notably, in the four long-term follow-up macaques, average hemoglobin A1c dropped by over 2% compared with peak values, whereas the average exogenous insulin requirement reduced by 49% 15 weeks after transplantation. Collectively, our findings show the feasibility of hPSC-islets for diabetic treatment in a preclinical context, marking a substantial step forward in clinical translation of hPSC-islets.

Precise organization of nanoparticles (NPs) into regularly well-defined arrays represents a continuing challenge in the development of high-performance metamaterials. Herein, zone-annealed diblock copolymers provide an effective medium for construction of periodically well-ordered arrays of NPs within mechanically enhanced nanocomposites. By integrating the dynamic self-consistent field theory for diblock copolymers and molecular dynamics for NPs, it is revealed that the emergence of response layers of asymmetric diblock copolymers induces the epitaxial assembly of NPs during the processing of hot zone annealing. In particular, the ability to kinetically control the assembly pathway of NPs enables them to be organized into hexagonally packed, defect-free arrays, with essentially the individual NP in a unit cell. Our simulations also show that the moving speed of annealing fronts and the concentration and radius of NPs all play important roles in engineering both the spatial arrangement and organization of NPs in a diblock copolymer matrix. Furthermore, the information from the simulations of diblock copolymer/NP mixtures is used to deduce mechanical responses of polymeric nanocomposites by the lattice spring model. The results reveal that the spatial arrangement and organization of NPs in the diblock copolymer matrix provide additional reinforcing elements to enhance the strength of structural materials. Merging the self-assembly of nanocomposites with the zone annealing processing can provide a means of kinetically controlling the assembly pathway for the achievement of regularly well-ordered arrays of polymer-embedded NPs with structural and optoelectronic functionalities.

The integration of the dynamic self-consistent field theory for polymer molecules and molecular dynamics for nanoparticles is proposed to model the structural evolution of nanocomposites in the course of zone annealing. Using computational modeling, we establish an effective approach to simultaneously tailor the spatial regularity of self-assembled nanostructures of diblock copolymers and the arrangement of nanoparticles within the matrix. As the spatially localized, mobile field of zone annealing is introduced into the hybrid organic/inorganic system, the nanocomposites re-assemble from the defective nanopatterns to the periodically well-ordered nanostructures, with the nanoparticles dispersed in the energetically favorable domains. In particular, because of the presence of response layers of diblock copolymers at the annealing front, the directional motion of nanoparticles within the matrix can be achieved by finely tuning the moving velocity and minimum Flory–Huggins interaction parameter of zone annealing. Furthermore, the regularity of self-assembled nanostructures and the spatial arrangement of nanoparticles are affected by the physiochemical properties of nanoparticles. Our theoretical findings present new opportunities to kinetically manipulate the self-assembled nanostructures of both the organic and inorganic components, which will impart their collective properties and the ultimate performances of nanocomposites.