The brain is limited in its capacity to repair following traumatic injury due to limited endogenous stem cell populations, and a physically and chemically inhibitory environment driven by a chronic inflammatory response. Cell therapies can provide a source of new cells to aid tissue regeneration, however survival is often poor, and cells can fail to integrate into the host tissue when injected, thereby diminishing therapeutic effects.

To aid tissue regeneration, biomaterials derived from extracellular matrix (ECM) may be used as scaffolds for cell delivery and are found to possess anti-inflammatory and immune modulating properties. However, the development of ECM materials for the brain have had limited success, due to the complex nature of the tissue and the low yield of material obtained.

The aim of this thesis was to develop a novel ECM biomaterial that may be used to mediate inflammation and improve therapeutic cell delivery outcomes after traumatic brain injury (TBI). Thermo-responsive, mechanically tuneable hydrogels were fabricated from decellularised porcine dura mater tissues, that form gel scaffolds in physiological conditions.

Dural ECM was extensively characterised using proteomic analysis and matrix vesicles were isolated to elucidate the biomolecular composition of these materials. Hydrogels were applied to in vitro assays designed to model important cellular aspects of secondary TBI.

A controlled cortical impact (CCI) mouse model of TBI was implemented to determine hydrogel biocompatibility and suitability as a cell delivery scaffold. Human neural stem cells, dura ECM hydrogel, or their combination, were injected at 7 days post-injury. Functional outcome and modulation of the astrocytic and microglial response were investigated up to 28 days post-transplantation. Findings demonstrated improved outcomes following treatment and promise for the further development of dural ECM hydrogels for the treatment of TBI.