polymers. Moreover, in order to use these biomaterials in brain injury therapy, we
should consider that neural progenitor cells (NPCs) receive instructive cues from
chemical and physical sources which affect differentiation and growth. Therefore,
conjugation of specific bioactive molecules/peptides onto the culture surface constitutes a good strategy to gain control on the signals that cells receive from external
stimuli. In this sense, a logical design of materials for tissue engineering applications,
including regeneration of damaged brain tissues, involves the incorporation of adhesive
peptide sequences and cytokines into material constructs to promote cell penetration
and host tissue integration by enabling cell–matrix and cell–cell interactions.
In this chapter, we summarize key results obtained in this field using self-healing
biohydrogels based on collagen type I, including both in vitro and in vivo studies.
2 Collagen and Collagen Hydrogels
Collagen is the main structural protein found in the ECM of connective tissues in the
body. It is the most abundant protein in mammals, and it represents approximately
30% of the whole-body protein content [8]. From a chemical point of view,
collagens are trimeric molecules composed of three polypeptide α-chains, which
contain the repeating sequence (G-X-Y) n , where X is normally proline and Y is
hydroxyproline. Such repeating pattern allows the formation of a triple helix,
so-termed tropocollagen, which is the most characteristic structural feature of the
collagen protein family. It is well established that subsequent stabilization upon
further packing of the tropocollagen subunits into fibrils eventually forms a 3D
collagen hydrogel. There are 29 collagen types reported in the literature, which differ
in size, structure, and functions [9].
Collagen [10] and hyaluronic acid (HA) [11] are the most common natural
polymers in neural tissue engineering. In particular, it has been reported that collagen
hydrogel scaffolds infused with nerve growth factor are capable of improving cell
viability in vitro [12]. Moreover, neurons cultured in collagen hydrogels have been
found to retain their capacity to generate spontaneous post-synaptic potentials,
demonstrating functional synapse formation [13]. Importantly, collagen hydrogels
without additional topographical features have also been used to treat spinal cord
injury in rats in vivo. The results have showed that these gels are biocompatible,
support axonal growth, and can improve limited functional recovery. In addition,
collagen-based hydrogels have also been used to differentiate NPCs into neurons
and glial cells and to support neurite outgrowth of CNS neurons [14].
Collagen type IV is widely presented in the adult nervous system where it forms
basement membranes of the BBB and neuromuscular junctions, being also associated to neurogenesis in the embryonic and adult brain. Collagen type I (hereinafter
referred to as collagen I) is one of the collagen types found in fractone, an extracellular matrix structure, which is present in the lateral wall of the ventricles. This is
relevant because such location constitutes one of the main neural stem cell (NSC)
niches in the adult brain [9]. As NSCs retain the ability to self-renew and produce the
major cell types of the brain, they have been on the focus of restorative therapy for
358
R. de la Cruz and D. D. Díaz
should consider that neural progenitor cells (NPCs) receive instructive cues from
chemical and physical sources which affect differentiation and growth. Therefore,
conjugation of specific bioactive molecules/peptides onto the culture surface constitutes a good strategy to gain control on the signals that cells receive from external
stimuli. In this sense, a logical design of materials for tissue engineering applications,
including regeneration of damaged brain tissues, involves the incorporation of adhesive
peptide sequences and cytokines into material constructs to promote cell penetration
and host tissue integration by enabling cell–matrix and cell–cell interactions.
In this chapter, we summarize key results obtained in this field using self-healing
biohydrogels based on collagen type I, including both in vitro and in vivo studies.
2 Collagen and Collagen Hydrogels
Collagen is the main structural protein found in the ECM of connective tissues in the
body. It is the most abundant protein in mammals, and it represents approximately
30% of the whole-body protein content [8]. From a chemical point of view,
collagens are trimeric molecules composed of three polypeptide α-chains, which
contain the repeating sequence (G-X-Y) n , where X is normally proline and Y is
hydroxyproline. Such repeating pattern allows the formation of a triple helix,
so-termed tropocollagen, which is the most characteristic structural feature of the
collagen protein family. It is well established that subsequent stabilization upon
further packing of the tropocollagen subunits into fibrils eventually forms a 3D
collagen hydrogel. There are 29 collagen types reported in the literature, which differ
in size, structure, and functions [9].
Collagen [10] and hyaluronic acid (HA) [11] are the most common natural
polymers in neural tissue engineering. In particular, it has been reported that collagen
hydrogel scaffolds infused with nerve growth factor are capable of improving cell
viability in vitro [12]. Moreover, neurons cultured in collagen hydrogels have been
found to retain their capacity to generate spontaneous post-synaptic potentials,
demonstrating functional synapse formation [13]. Importantly, collagen hydrogels
without additional topographical features have also been used to treat spinal cord
injury in rats in vivo. The results have showed that these gels are biocompatible,
support axonal growth, and can improve limited functional recovery. In addition,
collagen-based hydrogels have also been used to differentiate NPCs into neurons
and glial cells and to support neurite outgrowth of CNS neurons [14].
Collagen type IV is widely presented in the adult nervous system where it forms
basement membranes of the BBB and neuromuscular junctions, being also associated to neurogenesis in the embryonic and adult brain. Collagen type I (hereinafter
referred to as collagen I) is one of the collagen types found in fractone, an extracellular matrix structure, which is present in the lateral wall of the ventricles. This is
relevant because such location constitutes one of the main neural stem cell (NSC)
niches in the adult brain [9]. As NSCs retain the ability to self-renew and produce the
major cell types of the brain, they have been on the focus of restorative therapy for
358
R. de la Cruz and D. D. Díaz