Authors: Harmanvir Ghuman, Carrinton Mauney, Julia Donnelly, Andre R. Massensini, Stephen F. Badylak, Michel Modo
Summary: 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.
Source: Acta Biomaterialia; online 16 September 2018