Abstract

Biomaterials for cell replacement therapy could facilitate the delivery, function, and retrieval of transplanted therapeutic cells. However, the limited capacity to accommodate a sufficient quantity of cells in biomedical devices has hindered the success of clinical application, resulting from the suboptimal spatial organization of cells and insufficient permeation of nutrients in the materials. Herein, through the immersion-precipitation phase transfer (IPPT) process from polyether sulfone (PES), we develop planar asymmetric membranes with a hierarchical pore architecture spanning from nanopores (∼20 nm) in the dense skin and open-ended microchannel arrays with gradient pore size increasing vertically from microns to ∼100 μm. The nanoporous skin would be an ultrathin diffusion barrier, while the microchannels could support high-density cell loading by acting as separate chambers allowing uniform distribution of cells in the scaffold. Alginate hydrogel could permeate into the channels and form a sealing layer after gelation, which could slow down the invasion of host immune cells into the scaffold. The hybrid thin-sheet encapsulation system (∼400 μm thick) could protect allogeneic cells over half-year after intraperitoneal (IP) implantation in immune-competent mice. Such structural membranes and plastic–hydrogel hybrids of thin dimensions could find important applications in cell delivery therapy.