A novel peptide-based hydrogel that can be injected as a solid may one day be used to repair damaged human tissue, according to scientists at the University of Delaware, USA. The low viscosity gel could be used to deliver cells and pharmaceuticals.

Close up of the hydrogels (Image: Kathy F Atkinson/ University of Delaware, USA)Although insoluble in water, hydrogels are super-absorbent, have high water solvent content and high porosity for diffusion of cells and molecules. ‘[They] are easily made biocompatible and biodegradable,’ says Darrin Pochan, Associate Professor of Materials Science at the University of Delaware.

By producing a hydrogel based on a self-assembling peptide developed by the team (MAX1), researchers wanted to create a material that, once implanted into the human body, could become a scaffold for cells to hold onto and/or to grow new cells, such as fibroblasts, that form connective tissue, and osteoblasts, which form bone.

Smart materials

‘Designing peptides that intra-molecularly fold on cue has proven to be a general design paradigm leading to responsive smart materials – intra-molecular peptide folding [is linked] to the material characteristics,’ explains Pochan. ‘We have developed a hydrogelation system that is defined by this self-assembly.’

The peptide automatically folds into a particular shape in response to environmental stimuli such as pH, temperature, salt, cell growth, culture media and light. This means that the gelation process of the hydrogel is reversible. On exposure to, or removal of, an environmental stimuli, the hydrogel will either self-assemble or unfold, dissolving the nanostructure underlying the scaffold.

Pochan says, ‘Due to the self-assembled nature of the hydrogel, gel mechanical rigidity quickly recovers after the material experiences any amount of shear, such as a syringe injection. This re-healing behaviour provides the opportunity for cell encapsulation and subsequent injection into the body for in vivo tissue regeneration.’

He adds, ‘The ability to inject a solid, not a liquid, that turns into a gel after injection allows us to define a gel-cell construct ex vivo – defining stiffness, morphology, chemistry, cell density and cell distribution – and regain that construct in vivo after injection. Conventional gels and liquids are unable to do that in solution.’

Injectable solids

According to the team, which is also led by Professor Joel Schneider, the novel material is cytocompatible and antimicrobial. ‘We think the area of injectable solids will be huge in tissue engineering and cosmetic surgery,’ says Pochan.

Schneider is collaborating with Dr Joseph Bennett, a surgeon at the Helen F Graham Cancer Center, in Wilmington, USA, who specialises in liver tumours. Schneider says, ‘If almost 70% of [a liver] is lost to disease and removed, the remaining 30% can grow, affording a functional liver.’ The aim is to use hydrogels to deliver hepatocytes to ‘beef up’ the liver before surgery.

Professor Pankaj Vadgama, Director of the Interdisciplinary Research Centre in Biomedical Materials at Queen Mary, University of London, UK, comments, ‘3D hydrogels have been the focus of considerable effort as the support element for cells in the context of tissue engineering.’ He says the ‘most promising attribute’ of the research at Delware is the ability to inject the gel, implanting seeded cells inside the body without surgery.

But there is a long way to go. Vadgama adds, ‘Without adequate vascularisation and a good nutrient/oxygen supply, cells have a hard time even millimetres away from the surface. This technology is [a] valuable model in studying such dynamic processes and how these might couple into microenvironmental changes created by seeded cells.’