https://www.sciencedirect.com/science/article/pii/S1742706118305373
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.
Statement of Significance
Extracellular
matrix hydrogel promotes tissue regeneration in many peripheral soft
tissues. However, the brain has generally been considered to lack the
potential for tissue regeneration. We here demonstrate that tissue
regeneration in the brain can be achieved using implantation of ECM
hydrogel into a tissue cavity. We here demonstrate that a
structure-function relationship is key to promote tissue regeneration in
the brain. Specifically, weaker hydrogels that were retained in the
cavity underwent an efficient biodegradation within 14 days
post-implantation to promote a tissue restoration within the lesion
cavity. In contrast, stiffer ECM hydrogel only underwent minor
biodegradation and did not lead to a tissue restoration. Inductive
hydrogels weaker than brain tissue provide the appropriate condition to
promote an endogenous regenerative response that restores tissue in a
cavity. This approach offers new avenues for the future treatment of
chronic tissue damage caused by stroke and other acute brain injuries.
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