Injectable Hydrogels for Brain Tissue Regeneration after Traumatic Brain Injury
When TBI occurs, brain tissue swells, leading to the release of compounds that cause damage to the healthy tissue around it. This cell deterioration, along with the brain's poor ability to regenerate, leads to the formation of a lesion or cavity at the site that causes prolonged neurological impairment.
Conventional TBI treatments focus on managing brain tissue swelling at the primary site and reducing the effects of the secondary injury to healthy brain tissue. The next step may be neural cell transplantation, but despite moderate progress with other diseases, it has had limited success for TBI repair due to poor donor cell survival and functionality. The ongoing tissue inflammation and scarring at the lesion site, in addition to the lack of supportive tissue structure within the cavity, present a hostile environment that jeopardizes the survival of transplanted cells.
Researchers at Clemson University developed an animal model for building a new vascular network, providing a viable structure in which to place transplanted cells in TBI patients. The study used a contusion model of TBI in adult male rats. Using an injected hydrogel at the TBI lesion cavity, a vasculature network was reconstructed to support the arriving cells. This is the first time a well-structured vasculature network was formed within an injected hydrogel at the TBI lesion cavity without using angiogenic growth factors. CDMRP-funded researchers took it a step further and transplanted neural stem cells with neural differentiation factors to the TBI lesion using the hydrogel as a carrier. Results showed that significant functional recovery was found in the laboratory rats after 8 weeks of treatment.
"For cell replacement at the TBI lesion cavity, there is a critical need to pre-condition the lesion site with a vasculature network to support subsequently arriving neural cells," said Principal Investigator Ning Zhang, Ph.D., Assistant Professor of Bioengineering, Microbiology and Immunology, and Cell Bology and Anatomy at Clemson University. "To this end, we developed an in-situ cross-linking hydrogel with similar mechanical property to that of native brain tissue and cell adhesive motifs so TBI can be treated more effectively."
