Application of Temporary, Cell-Containing Alginate Microcarriers to Facilitate the Fabrication of Spatially Defined Cell Pockets in 3D Collagen Hydrogels.

Mimicking the complexity of natural tissue is a major challenge in the field of tissue engineering. Here, a facile 2-step fabrication method to prepare 3D constructs with distinct regions of high cell concentrations and without the need for elaborate equipment is proposed. The initial incorporation of cells in a sacrificial alginate matrix allows the addition of other, cell relevant biopolymers, such as, collagen to form a spatially confined, interpenetrating network at the microscale. A layered structure at the macroscale can be achieved by incorporating these cell-containing microspheres in thin collagen layers. Cells are locally released by de-gelling the alginate matrix and their attachment to the collagen hydrogel layers has been studied. The use of the murine pre-osteoblast cell line MC3T3-E1 as an example cell line shows that the cells behave differently in their cell migration pattern based on the initial composition of the alginate microspheres.