Birch Tree Scaffold

by Harald Zähringer, Labtimes 07/2012

Woodpulp is fabricated in tremendous amounts as a raw material for the production of paper. It may, however, also be reconditioned to nanofibrillar cellulose hydrogel, suitable for 3D cell culture.

Cells growing in tissues are embedded in an extracellular matrix composed of fibrous proteins, such as collagen, elastin and laminin, which are interwoven into a nano-fibrillac-network. Three dimensional (3D) cell culture techniques try to mimic the in vivo situation of cells in their natural environment. Instead of attaching to the surface of cell culture dishes as in traditional 2D cell culture, 3D cultured cells are grown on scaffolds that resemble the extracellular matrix. The cells are supported by the scaffold and may form cell-to-cell contacts, spreading in all three dimensions.

Bleached pulp from Finnish birch trees provides the raw material for a new 3D cell culture scaffold, made of nanofibrillar cellulose hydrogel.

Nanofibrillar network

Hydrogels are a very popular type of 3D scaffold. They are composed of cross-linked polymers forming a network of pores that may retain water and enable the transport of nutrients, gases and bioactive agents. Various synthetic or natural polymers, e.g. peptides, polysaccharides, polyethylene glycol and polyvinyl alcohol have been used to prepare hydrogels. However, several cross-linking steps are required to connect the components of these hydrogel matrices. Bacterial cellulose, which doesn’t require cross-linking, has also been used as an alternative fibrous material suitable for the construction of scaffolds for 3D cell culture.

But what about hydrogel scaffolds made of plant cellulose?

A team centred around Marjo Yliperttula from the Division of Biopharmaceutics and Pharmacokinetics at the University of Helsinki explored this question (Bhattacharya et al., J. Control Release, 2012, in press). It is, incidentally, not accidental that a Finnish group took a closer look at this matter. The Finnish pulp and paper industry has a deep knowledge of plant cellulose conditioning and dominates the European paper market. Actually, chances are good that the Tips and Tricks article you read on this page is printed on paper fabricated by a Finnish paper giant.

Yliperttula’s group teamed up with the Finnish pulp and paper company UPM-Kymmene Corporation to produce a nanofibrillar cellulose (NFC) hydrogel from bleached birch pulp applying an industrial fluidiser. To maintain microbiological purity, the whole process was done on sterilised machinery.

Similar to the extracellular matrix

The group first checked some physical and rheological properties of the prepared NFC hydrogel. The diameter of individual fibres is close to seven nanometres and fibre bundles have a fibril width of between 20 and 30 nanometres. These dimensions are very similar to those found for native collagen. According to the authors, the viscosity properties are comparable to that of the extracellular matrix.

The real Lackmus-test for the NFC hydrogel scaffold, however, was the 3D culturing of the hepatic cell lines HepaRG and HepG2. NFC hydrogel brilliantly passed the test. Both cell lines formed three-dimensional multicellular spheroids in native NFC hydrogel and secreted albumin, a typical marker for differentiating hepatocytes. The Finns believe that the beneficial properties of NFC in 3D cell culturing may be traced back to the similar structures of NFC hydrogel and extracellular matrix.

Looks like 3D cell culturers may start ordering their future scaffolds from paper mills.

Last Changed: 06.02.2013