Bioengineers at Harvard University have developed an elastic material that can be injected into the body to deliver drugs or stem cells before degrading safely.
The biocompatible technology, described in the Proceedings of the National Academy of Sciences, could find use in minimally invasive therapeutic applications, including regenerative medicine.
‘What we’ve created is a three-dimensional structure that you could use to influence the cells in the tissue surrounding it and perhaps promote tissue formation,’ said principal investigator David J Mooney, the Robert P Pinkas Family professor of bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS) and a core faculty member at the Wyss Institute for Biologically Inspired Engineering at the university.
‘The simplest application is when you want bulking,’ Mooney said in a statement. ‘If you want to introduce some material into the body to replace tissue that’s been lost or that is deficient, this would be ideal. In other situations, you could use it to transplant stem cells if you’re trying to promote tissue regeneration, or you might want to transplant immune cells if you’re looking at immunotherapy.’
Consisting primarily of alginate, a seaweed-based jelly, the injectable sponge contains networks of large pores, which allow liquids and large molecules to easily flow through it.
Mooney and his research team demonstrated that live cells can be attached to the walls of this network and delivered intact along with the sponge through a small-bore needle.
Mooney’s team also demonstrated that the sponge can hold large and small proteins and drugs within the alginate jelly itself, which are gradually released as the biocompatible matrix starts to break down inside the body.
Normally, a scaffold such as this would have to be implanted surgically. Gels can also be injected, but until now these gels would not have carried any inherent structure; they would simply flow to fill whatever space was available.
‘Our scaffolds can be designed in any size and shape and injected in situ as a safe, preformed, fully characterised, sterile and controlled delivery device for cells and drugs,’ said lead author Sidi Bencherif, a postdoctoral research associate in Mooney’s lab at SEAS and at the Wyss Institute.
The sponge-like gel is formed through cryogelation; as the water in the alginate solution starts to freeze, pure ice crystals form, which makes the surrounding gel more concentrated as it sets.
Later on, the ice crystals melt, leaving behind a network of pores. By carefully calibrating this mixture and the timing of the freezing process, Mooney, Bencherif and colleagues found that they could produce a strong and compressible gel.
Bencherif said: ‘These injectable cryogels will be especially useful for a number of clinical applications, including cell therapy, tissue engineering, dermal filler in cosmetics, drug delivery and scaffold-based immunotherapy.
‘Furthermore, the ability of these materials to reassume specific, predefined shapes after injection is likely to be useful in applications such as tissue patches where one desires a patch of a specific size and shape and where one desires to fill a large defect site with multiple smaller objects.
‘These could pack in such a manner to leave voids that enhance diffusional transport to and from the objects and the host, and promote vascularisation around each object.’