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, we propose a facile 2-step fabrication method to prepare three-dimensional constructs with distinct regions of high cell concentrations and without the need for elaborate equipment. 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 showed that the cells behave differently in their cell migration pattern based on the initial composition of the alginate microspheres. This article is protected by copyright. All rights reserved.