title: Design for a lithographically patterned bioartificial endocrine pancreas.
abstract: Cell encapsulation provides a means to transplant therapeutic cells for a variety of diseases including diabetes. However, due to the large numbers of cells, approximately on the order of a billion, that need to be transplanted for human diabetes therapy, adequate mass transport of nutrients such as oxygen presents a major challenge. Proof-of-concept for the design of a bioartificial endocrine pancreas (BAEP) that is optimized to minimize hypoxia in a scalable and precise architecture is demonstrated using a combination of simulations and experiments. The BAEP is composed of an array of porous, lithographically patterned polyhedral capsules arrayed on a rolled-up alginate sheet. All the important structural variables such as the capsule dimensions, pore characteristics, and spacing can be precisely engineered and tuned. Further, all cells are encapsulated within a single device with a volume not much greater than the total volume of the encapsulated cells, and no cell within the device is located more than 200 μm from the surrounding medium that facilitates efficient mass transport with the surroundings. Compared with gel-based encapsulation methods, our approach offers unprecedented precision and tunability of structural parameters as well as the volume of the encapsulated cells and consequently the amount of secreted insulin. Our work highlights the utility of lithography and self-assembly in the fabrication of micro- and nanostructured three-dimensional structures that simulate the function of natural endocrine organs.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Park
authors.forename: Yevgeniy V
authors.initials: YV
authors.lastname: Kalinin
authors.forename: Sachin
authors.initials: S
authors.lastname: Kadam
authors.forename: Christina L
authors.initials: CL
authors.lastname: Randall
authors.forename: David H
authors.initials: DH
authors.lastname: Gracias
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D017076:Computer-Aided Design; D004867:Equipment Design; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D049329:Nanostructures; D010100:Oxygen / Q000378:metabolism; D016062:Porosity; D013499:Surface Properties; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D007328:Insulin; D005947:Glucose; D010100:Oxygen
keywords: BioMEMS; Bioartificial pancreas; Cell encapsulation therapy; Diabetes; Insulin; Nanotechnology