Background: Approximately 700,000 Australians suffer from a brain injury, along with the time and financial burden on our healthcare system. However, there is no long-lasting approved treatments for brain injury. Engineered biomaterials for delivery and support of cells hold significant promise for the replacement and repair of damaged or diseased brain tissues. Currently, there are critical issues of their use post-transplantation; namely, hypoxia, poor cell survival and cell differentiation.

Methods: In this work, we have engineered oxygenating hydrogels by protein-engineering techniques and solid-phase peptide synthesis. We have characterised those oxygenating hydrogels and explored oxygen release kinetics, followed by the assessment of the functional integration in vivo after 28 days.

Results: The oxygenating hydrogels can perform nanofibrous scaffolds with mechanical support, as well as being the functional state for oxygen binding and releasing. The oxygenating hydrogels have no effect on host inflammatory response while supporting cell survival and graft innervation. Most importantly, the oxygenating hydrogel can promote the differentiation of primary stem cells into neurons, which are considered essential for brain injury.

Discussions and Conclusions: We have successfully engineered oxygenating hydrogels that are capable of concomitantly delivering stem cells and oxygen within the brain to support engraftment. These oxygenating hydrogels can promote extensive innervation, ensuring functional synaptic connectivity while increasing of neuronal differentiation, demonstrating modulating cell fate specification. These oxygenating hydrogels are the promising approach for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.