invivoid® is the collective name of cell culture methodologies TOPPAN Holdings Inc. and Osaka University has developed together. Each methodology has promising applications according to its own advantages.

Methodology 1 :
CVA(Cell Viscous Assembly) Method


How it works

By adding heparin and type I collagen to cell suspension, a viscous body is formed by the strong aggregation of cells after centrifugation. Adhesion of cells is induced by the collagen, resulting in three-dimensional tissue. Various types of cells in the tissue mutually interact and align themselves, creating tissue with structures such as a network of capillary blood vessels.
A layer of cells up to 300 μm thickness can be fabricated in one step. Tissues with multi-layer structure can easily be constructed by repeating this step.

Key Advantages

Layered Co-Culture

Cell positions in layered tissue can be designed, constructed, and maintained during culture.


Example of tissue with five-layer structure

Self-Assembled Structures

Self-assembled structures, such as capillary blood vessels with vascular endothelial cells, can be formed.


Example of co-cultured liver tissue with sinusoidal network
*green: anti-albumin antibody (Hepatocyte)
*red: anti-CD31 antibody (Sinusoidal Endothelial Cells)

Diverse Cell Sources

- Patient-derived cells
- Cell lines
- iPSC / ESC-derived cells
- etc.


Example of culturing patient-derived primary cancer cells. Cancer cells grew only in invivoid® co-culture model using inexpensive growth factor free medium (DMEM).


Methodology 2 :
CMF(Collagen Microfiber) Method


How it works

Homogenization and lyophilization of collagen sponge creates highly dispersible fragmented collagen fibers.
Unlike the CVA method, this method produces thick, high collagen density tissue.
Tissues up to 5 mm thick can be created in a single step, without the need to layer cells one by one.


Key Advantages

High cell support/water dispersibility

Unlike gelatin or collagen peptides that have been chemically degraded, CMF consists of fine fibers that maintain the inherent water-insolubility of collagen while significantly improving dispersibility.


Comparison with chemically degraded gelatin and collagen peptides

Fine fiber formation through the defibration of collagen

Easily dispersible in culture medium, ideal as a scaffold for cells


Observed images and calculated fiber thickness in optical microscope and scanning electron microscope

Enables the production of collagen-dense tissues with high thickness

Cells are dispersed to the interior and survive even in tissues thicker than 1 mm


3D cellular tissue section using cancer cells and fibroblasts

Thickness and stiffness are controllable

Thickness and stiffness can be controlled by changing the amount of CMF in the tissue


Elastic modulus when CMF amount is controlled and thickness/strength is changed. Cell position control and analysis such as migration progress measurement is also possible.