Method and apparatus for spatial control of cellular growth
A three-dimensional cell growth containment article is described, which includes a molded body channelized by removal of sacrificial channelizing element(s) therefrom, so that the molded body contains one or more channel(s) therein, with a matrix material in at least one of such channel(s) that is supportive of three-dimensional cell growth in the matrix material. A method for making such articles is also described, in which a molded body is formed with one or more sacrificial channelizing element(s) therein, following which the sacrificial channelizing element(s) are removed. The three-dimensional cell growth containment articles of the present disclosure may be utilized in any applications in which there exists a need to reproducibly generate three-dimensional cellular structures, e.g., islet transplantation for diabetes treatment, transplantation of hormone secreting cells, cellular scaffolds for wound healing, and generation of tissue engineering structures to regain structural usefulness for orthopedic applications.
1 . A three-dimensional cell growth containment article for in vivo insulin production in a human or veterinary subject, said article comprising a molded body containing a hollow core therein, with a three-dimensional cellular scaffold comprising matrix material contained in said hollow core, comprising a three-dimensional cell population of islet cells in the matrix material for said in vivo insulin production in a human or veterinary subject when introduced into said subject, wherein the molded body is sufficiently permeable for insulin, glucose, and oxygen exchange in said subject without allowing antibodies to reach the islet cells, wherein the matrix material comprises alginate cross-linked with calcium cations and a cell attachment signal agent comprising arginylglycylaspartic acid (RGD), and wherein the molded body is multi-layered, with the hollow core circumscribed by an alginate-polyacrylamide layer, and an outermost layer comprising high-G alginate and vascular endothelial growth factor C (VEGF-C).
2 . The three-dimensional cell growth containment article of claim 1 , wherein the high-G alginate has a G:M ratio of guluronic acid (G):mannuronic acid (M) that is greater than 1.5.