Another dimension in cell biology

PuraMatrix, made from peptide hydrogels, is already finding applications in cell-based assays and research into cell migration and invasion, neurite outgrowth, hepatocyte functionality and toxicity, according to 3DM's president, Zen Chu.

It has been understood for more than a decade that cells behave very differently when they are in three dimensions, but designing an in vitro​ environment that can mimic the in vivo​ state has been difficult. In the body, cells are affected by signals from their neighbours and the extracellular matrix (ECM) that surrounds them, and these signals are absent in a 2D plate.

This raises the fundamental question of the reliability of data generated in cell-based screening. If the readout from these cells does not reflect their state in vivo​, then companies may be missing potentially valuable drugs in their drug screens, or bringing forward compounds on spurious grounds.

3DM's PuraMatrix hydrogels can be used to create defined three-dimensional microenvironments that more closely mimic the natural environment for a cell, said Chu. Importantly, the gels are supplied in a 'bare' state, meaning that researchers can modify them by adding in signals - such as growth factors, cytokines or even other cell types - to make them behave in a manner closer to their natural state.

And 3DM claims that using these cellular scaffolds leads to an improvement in the quality of data if generated in whole cell assays. This is a view held by Mihael Polymeropoulos, a noted cell biologist and formerly head of pharmacogenetics at Novartis, who said in an article in Nature​ (21 August 2003 issue) that "in 10 years, anyone trying to use 2D analyses to get relevant and novel biological information will find it difficult to get funded."​

The US National Institutes of Health has earmarked $40 million for cell culture research - with a particular focus on 3D technologies - in recognition of the importance of these factors.

Aside from a hike in data quality, another advantage is that tissue-like structures can be made for assay purposes, potentially cutting down on the number of animals used for expensive in vivo​ testing, according to 3DM.

Drug discovery efforts at major pharmaceutical and biotechnology companies are beginning to adopt 3D culture techniques in their cell-based assays, especially in the context of drug screening, toxicology assays, high content screening, and bioproduction, it said.

Competitive position​

Chu told In-Pharmatechnologist.com that PuraMatrix has advantages over other products used to generate 3D environments in cell culture. For example, animal-based products (which tend to be derived from collagen or gelatine) can generate their own signals that can effect the behaviour of cells.

Meanwhile, synthetic rivals, such as Becton Dickinson's Matrigel, cannot create matrices that are small enough to reflect the natural ECM environment, with fibres that are three times the size of those achievable using PuraMatrix. Aside from BD and 3DM, just about all the other matrices used are home-grown in the lab, noted Chu.

3DM will be showcasing the materials, which are already on sale through 3DM's website, at the 43rd annual conference of the American Society for Cell Biology (ASCB) in San Francisco, starting this Saturday.

There are currently three grades of PuraMatrix available. The regular, research-grade product is already available from the manufacturer but will be distributed on a worldwide basis by an international supplier starting next year, said the firm.

A second, stronger product - PuraMatrixCST - is a stronger version of the gel that is mouldable into shapes and can withstand physical loading in combination with cell culture conditions. This has already been used to create cartilage tissue ex vivo​ of a quality that has never been achieved before.

Finally, 3DM has developed PuraMatrixGMP, a clinical grade of the gel that can be used for biopharmaceutical production and the expansion of cells used in cell-based therapies. This is due to reach the market next year.

For more information on these products, visit 3DM's website​ or e-mail fnyrf@chenzngevk.pbz​.