Hot communication: Enzyme-triggered cell attachment to hydrogel surfaces

Hot communication: Enzyme-triggered cell attachment to hydrogel surfaces

1. Could you explain the significance of your article to the non-specialist?
In living systems, the behaviour of cells (differentiation, migration, etc) is dictated by biochemical signals in the gel-like material that surrounds them. A number of these ligands are activated when required in response to enzymes that are secreted by the cells, thereby providing molecular feed-back systems that allow cells to adapt to their environment. We set out to mimic such a process in man-made material and develop surfaces that can be switched between a bio-inert and bioactive state in response to an enzyme. Our proof-of-concept system is based on a surface-bound peptide ligand that instructs cells to attach. We rendered this ligand switchable between a non cell adhesive (off) state and an adhesive (on) state. This switchable ligand was immobilised on a hydrogel surface, providing an inert surface that be rendered cell adhesive on-demand.
"The work has been developed in the context of developing smart implant coatings"

2. What has motivated you to conduct this work?
We are interested in the ingenious solutions that nature has devised for designing functional materials. It is a major challenge to accurately mimic these methods and put them to use in new and useful materials for biology and medicine. The ability to develop materials that can direct a complex biological system such as a cell attachment by using very simple systems is challenging, and it also has useful applications. The work described in this article is developed in the context of developing smart implant coatings, in collaboration with one of the UK's leading medical devices companies (Smith & Nephew).

3. Where do you see this work developing in the future?
To our knowledge this is the first example of a synthetic enzyme-responsive surface that directs cell behaviour and we expect other systems to emerge. Future systems may trigger more complex cell behaviour, including directed wound healing and stem cell differentiation in the context of organ repair.

4. Are there any particular challenges facing future research in this area?
One important scientific challenge is to identify the biochemical signals that direct medically relevant cell behaviour and to incorporate these signals onto 2D surfaces or in a 3D scaffold gel matrix materials where they are only activated when required. Close collaborations between (stem) cell biologists, biomedical engineers, chemists, and materials scientists may ultimately give rise to a range of materials that guide cell behaviour in pre-defined ways. The main challenge is to closely mimic biology, while keeping the systems simple, cheap, robust and reproducible thereby combining the advantages of synthetic systems with the versatility of biology.