Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume.

Abstract

In situ gelation of ECM is essential for its retention within a tissue cavity. The brain is a unique environment with restricted access that necessitates image-guided delivery through a thin needle to access tissue cavities caused by stroke, as well as other conditions, such as traumatic brain injury or glioma resection. Knowledge about a brain tissue response to implanted hydrogels remains limited, especially in terms of long-term effects and potential impact on behavioral function. We here address the long-term retention of hydrogel within the brain environment, its impact on behavioral function, as well as its ability to reduce further tissue deformation caused by stroke. This study highlights considerable differences in the brain's long-term response to an ECM hydrogel compared to peripheral soft tissue. It underlines the importance of understanding the effect of the structural presence of a hydrogel within a cavity upon host brain tissue and behavioral function. As demonstrated herein, ECM hydrogel can fill a cavity long-term to reduce further progression of the cavity, while potentially serving as a reservoir for local drug or cell delivery.