The viability of xenotransplanted cells could be dramatically improved through immunoisolation by permselective encapsulation. The ideal capsule would simultaneously protect the cell from immunological attack, transport nutrients, and release therapeutic cell metabolites (e.g., insulin). Despite recent progress, persistent challenges include the lack of fine control over pore size and encapsulation thickness, the latter leading to mass transport limitations, cell necrosis, and slow cellular response to external stimuli. Material instability and bio-incompatibility also challenge cell encapsulation.
An exploratory research effort is proposed for the formation of permselective coatings on porcine pancreatic islets using silica nanoparticles. Such coatings may allow unprecedented control over thickness, pore size and active chemical functionality. The proposed work will benefit from collaborations with The Diabetes Institute at the University of Minnesota and derives from the recent identification of a benign (i.e., near-physiological conditions) and controllable means for synthesizing stable silica nanoparticles from 5 to 40 nm, and their ordering into colloidal crystal arrays and thin films.
The infliction of more than twenty million Americans with diabetes motivates the proposed research which aims to realize a novel and potentially high impact solution to the challenging problem of islet xenotransplantation. The success of the proposed initiative is of direct interest to the development of novel permselective membrane materials and applications. In addition, it stands to establish fundamental understanding of nanoparticle-cell association for mass transport control, the implications of which may ultimately influence targeted drug and DNA delivery and non-invasive cellular imaging and tracking.
