into the graft regions to release various cytotoxic cytokines. It was previously
reported that the use of materials such as hydrogels would be beneficial to the
protection of transplanted cells from inflammatory responses in the brain. NakajiHirabayashi’s results demonstrated that the infiltration of microglia is inhibited at the
early stage after transplantation, most likely due to the effect that the collagen
hydrogel acts as a physical barrier against microglial infiltration. Although a collagen hydrogel itself may also initiate inflammation, it was speculated that this is
overwhelmed by the effect of isolating graft cells from microglia.
5 Concluding Remarks
In conclusion, taking advantage of their tunable physical, chemical, and biological
properties, 3D biohydrogels made of collagen type I have shown great potential for
brain injury therapy. Among other features, these hydrogels are biocompatible,
noncytotoxic, and self-healable after injection, which is a major requirement for
in vivo applications in neuroregeneration. Although collagen does not naturally
occur in the brain, it has been demonstrated that collagen type I, which resides in
the basal lamina of the subventricular zone in adults, supports neural cell attachment,
axonal growth, and cell proliferation due to its intrinsic content of specific cellsignaling domains.
The results derived from the studies summarized in this chapter illustrate the
importance of several aspects such as (1) the necessary optimization of cell systems
before attempting cell replacement in vivo, (2) the combination of the gel matrix
with adhesive peptide sequences and proteins with appropriate cell attachment sites,
(3) the use of SCs and their alignment within the guidance channels for the
regeneration process, and (4) the appropriate stiffness, growth factor sequestering
ability, and injectability feature of the biohydrogel system.
Despite the promising results obtained during the last decade in both in vitro and
in vivo models, more detailed mechanistic studies are still necessary to understand
the function of collagens in the brain, which should be correlated to the effects
obtained during the use of their hydrogels in brain therapy. For instance, additional
studies are still necessary to visualize the interactions of collagens with other ECM
molecules, cell surface receptors, and downstream signaling pathways, which is
critical to understand the underlying connection between the presence of collagen
and certain pathogenesis in the nervous system. Furthermore, future studies involving specific functionalization of the collagen hydrogel would be important to release
on demand biological cues, glial scar modulating enzymes, or pro-survival factors
for in vivo therapy. In addition, advances in microfabrication techniques will likely
expand the use of biohydrogel scaffolds in neuroregeneration. In any event, any new
developed collagen-based hydrogel should be thoroughly tested for immuno-/
allergenicity prior to their use in clinical applications.
Self-Healing Collagen-Based Hydrogel for Brain Injury Therapy
375
reported that the use of materials such as hydrogels would be beneficial to the
protection of transplanted cells from inflammatory responses in the brain. NakajiHirabayashi’s results demonstrated that the infiltration of microglia is inhibited at the
early stage after transplantation, most likely due to the effect that the collagen
hydrogel acts as a physical barrier against microglial infiltration. Although a collagen hydrogel itself may also initiate inflammation, it was speculated that this is
overwhelmed by the effect of isolating graft cells from microglia.
5 Concluding Remarks
In conclusion, taking advantage of their tunable physical, chemical, and biological
properties, 3D biohydrogels made of collagen type I have shown great potential for
brain injury therapy. Among other features, these hydrogels are biocompatible,
noncytotoxic, and self-healable after injection, which is a major requirement for
in vivo applications in neuroregeneration. Although collagen does not naturally
occur in the brain, it has been demonstrated that collagen type I, which resides in
the basal lamina of the subventricular zone in adults, supports neural cell attachment,
axonal growth, and cell proliferation due to its intrinsic content of specific cellsignaling domains.
The results derived from the studies summarized in this chapter illustrate the
importance of several aspects such as (1) the necessary optimization of cell systems
before attempting cell replacement in vivo, (2) the combination of the gel matrix
with adhesive peptide sequences and proteins with appropriate cell attachment sites,
(3) the use of SCs and their alignment within the guidance channels for the
regeneration process, and (4) the appropriate stiffness, growth factor sequestering
ability, and injectability feature of the biohydrogel system.
Despite the promising results obtained during the last decade in both in vitro and
in vivo models, more detailed mechanistic studies are still necessary to understand
the function of collagens in the brain, which should be correlated to the effects
obtained during the use of their hydrogels in brain therapy. For instance, additional
studies are still necessary to visualize the interactions of collagens with other ECM
molecules, cell surface receptors, and downstream signaling pathways, which is
critical to understand the underlying connection between the presence of collagen
and certain pathogenesis in the nervous system. Furthermore, future studies involving specific functionalization of the collagen hydrogel would be important to release
on demand biological cues, glial scar modulating enzymes, or pro-survival factors
for in vivo therapy. In addition, advances in microfabrication techniques will likely
expand the use of biohydrogel scaffolds in neuroregeneration. In any event, any new
developed collagen-based hydrogel should be thoroughly tested for immuno-/
allergenicity prior to their use in clinical applications.
Self-Healing Collagen-Based Hydrogel for Brain Injury Therapy
375