Extracellular matrix (ECM) hydrogel promotes tissue regeneration in many peripheral soft tissues. However, the brain has generally been considered to lack the potential for tissue regeneration. In their study published in Acta Biomaterialia, McGowan Institute for Regenerative Medicine affiliated faculty member Michel Modo, PhD, Professor in the Department of Radiology at the University of Pittsburgh with secondary appointments in the Department of Bioengineering and the Center for Neural Basis of Cognition, and McGowan Institute Deputy Director Stephen Badylak, DVM, PhD, MD, Professor in the Department of Surgery at the University of Pittsburgh and Director of the Center for Pre-Clinical Tissue Engineering within the Institute, demonstrated that tissue regeneration in the brain can be achieved using implantation of ECM hydrogel into a tissue cavity. They and the research team further demonstrated that a structure-function relationship is key to promote tissue regeneration in the brain. This approach offers new avenues for the future treatment of chronic tissue damage caused by stroke and other acute brain injuries.
The scientists concluded that the present study suggests that implantation of ECM hydrogel can lead to an induced regeneration of brain tissue. Although further optimization and a better mechanistic understanding is required to afford greater control over the processes involved in tissue regeneration, in situ engineering of brain tissue using inductive biomaterials is encouraging and opens new therapeutic avenues.
Read the paper’s abstract:
The brain is considered to have a limited capacity to repair damaged tissue and no regenerative capacity following injury. Tissue lost after a stroke is therefore not spontaneously replaced. Extracellular matrix (ECM)-based hydrogels implanted into the stroke cavity can attract endogenous cells. These hydrogels can be formulated at different protein concentrations that govern their rheological and inductive properties. We evaluated histologically 0, 3, 4 and 8 mg/mL of porcine-derived urinary bladder matrix (UBM)-ECM hydrogel concentrations implanted in a 14-day old stroke cavity. Less concentrated hydrogels (3 and 4 mg/mL) were efficiently degraded with a 95% decrease in volume by 90 days, whereas only 32% of the more concentrated and stiffer hydrogel (8 mg/mL) was resorbed. Macrophage infiltration and density within the bioscaffold progressively increased in the less concentrated hydrogels and decreased in the 8 mg/mL hydrogels. The less concentrated hydrogels showed a robust invasion of endothelial cells with neovascularization. No neovascularization occurred with the stiffer hydrogel. Invasion of neural cells increased with time in all hydrogel concentrations. Differentiation of neural progenitors into mature neurons with axonal projections was evident, as well as a robust invasion of oligodendrocytes. However, relatively few astrocytes were present in the ECM hydrogel, although some were present in the newly forming tissue between degrading scaffold patches. Implantation of an ECM hydrogel partially induced neural tissue restoration, but a more complete understanding is required to evaluate its potential therapeutic application.
Abstract (Biodegradation of ECM hydrogel promotes endogenous brain tissue restoration in a rat model of stroke. Harmanvir Ghuman, Carrinton Mauney, Julia Donnelly, Andre R. Massensini, Stephen F. Badylak, Michel Modo. Acta Biomaterialia; online 16 September 2018.)