Title:
In Vitro Construction of Vascularized 3D-Human Tissue Models for Tissue Engineering & Drug Delivery System

 

Michiya Matsusaki (Associate professor)
Department of Applied Chemistry, Graduate School of Engineering, Osaka University

 

Abstract:
In vitro development of highly-organized three dimensional (3D)-engineered tissues consist of multiple types of cells and ECM, which possess a similar structure and function as natural tissues, is a key challenge for tissue engineering and pharmaceutical assay. Especially modulation of 3D-cell-cell interaction inside the 3D-artificial tissues is one of the significant issues.
We have developed a simple and unique bottom-up approach, “hierarchical cell manipulation”, using nanometer-sized Layer-by-Layer films consisting of fibronectin and gelatin (FN-G) as a nano-extracellular matrix (nano-ECM) [1]. The FN-G nanofilms were prepared directly on the cell surface, and we discovered that at least 6 nm thick FN-G films acted as a stable adhesive surface for adhesion of the second cell layer. We have also developed a rapid bottom-up approach, “cell-accumulation technique”, by a single cell coating using FN-G nanofilms, because the fabrication of two-layers (2L) was limitation through the above technique due to the time required for stable cell adhesion [2]. This rapid approach easily provided more than twenty-layered (over 150 µm) 3D-tissues after only one day of incubation. Moreover, fully and homogeneously vascularized tissues of 1 cm width and 100 µm height were obtained by a sandwich culture of the endothelial cells. The hierarchical cell manipulations will be promising to achieve one of the dreams of biomedical field, in vitro automatic creation of artificial 3D-tissue models [3]. We are demonstrating in vitro reconstruction of metastasis early processes, invasion, intravasation, mobilization and extravasation of human invasive carcinomas using artificial 3D-blood and lymphatic capillaries.

 

References:
[1] M. Matsusaki et al, Angew. Chem. Int. Ed., 46, 4689 (2007).
[2] M. Matsusaki et al., Adv. Mater. 24, 454 (2012).
[3] M. Matsusaki et al., Adv. Healthcare Mater. 2, 534 (2013).