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transplanted cells, uncontrolled cell differentiation, non-sustained delivery of
growth factors, and ineffective engraftment with the host tissue. A tissue engineering approach provides an alternative for treating the damaged brain, as it provides
multifunctional solutions to overcome the limitations of conventional approaches.
In this chapter, we focus on the limitations of current pro-angiogenic therapies using
vascular growth factors and some recent advances using engineered biomaterials
and drug delivery systems for brain tissue repair.
7.2 The Neurovascular Damage after Stroke
The neuron has traditionally been viewed as the centerpiece of the mammalian central nervous system (CNS) because of its fundamental role in neurotransmission.
Thus, the classical approach of neurorepair was solely based on neuroprotection and
neuron cell replacement. Over the past decade, remarkable advances have been
made in understanding the mechanisms of neurorepair, such as neurogenesis (formation of new neurons), angiogenesis (formation of new blood vessels), gliogenesis
(formation of new glial cells), and re-myelinization, among other processes. These
discoveries changed the classical view of brain repair, providing greater understanding of the brain as a whole and supporting the hypothesis that saving neurons alone
may not be sufficient [8]. This concept of a “neurovascular unit” defines tissue
remodeling as a highly dynamic process between vascular, neuronal, and glial cells.
After stroke, these cells respond to injury in a coordinated and synergistic manner,
releasing molecular signals and trophic factors that mutually influence each other to
create a pro-repair environment where tissue regeneration and neurological recovery may take place [32]. In recent years, the promotion of vascular growth and
remodeling in the injured brain is increasingly recognized as a particularly promising approach to treat brain illnesses [9]. This approach has brought confidence that
stimulating the growth of new vessels both in and around the ischemic site may
stabilize brain perfusion and promote tissue repair through neuronal survival, plasticity, and functional recovery [13, 14, 18].
7.3 Spatiotemporal Dynamic of Brain Angiogenesis
At the core of an ischemic incident, the severe energy and glucose loss induces a
rapid neuronal death, leaving behind a necrotic site within minutes after the stroke
onset. However, the surrounding area, called penumbra, has a mild-to-moderate
vascular compromise, where the energy deficit is less severe and collateral vessels
maintain a certain degree of blood flow (Fig. 7.1).
This area may be rescued if blood flow is restored [10]. Increasing evidence, in
both human stroke patients and animal experimental models, suggests that angiogenesis occurs in those penumbra areas [28]. Indeed, an increasing body of evidence
L. R. Nih et al.
transplanted cells, uncontrolled cell differentiation, non-sustained delivery of
growth factors, and ineffective engraftment with the host tissue. A tissue engineering approach provides an alternative for treating the damaged brain, as it provides
multifunctional solutions to overcome the limitations of conventional approaches.
In this chapter, we focus on the limitations of current pro-angiogenic therapies using
vascular growth factors and some recent advances using engineered biomaterials
and drug delivery systems for brain tissue repair.
7.2 The Neurovascular Damage after Stroke
The neuron has traditionally been viewed as the centerpiece of the mammalian central nervous system (CNS) because of its fundamental role in neurotransmission.
Thus, the classical approach of neurorepair was solely based on neuroprotection and
neuron cell replacement. Over the past decade, remarkable advances have been
made in understanding the mechanisms of neurorepair, such as neurogenesis (formation of new neurons), angiogenesis (formation of new blood vessels), gliogenesis
(formation of new glial cells), and re-myelinization, among other processes. These
discoveries changed the classical view of brain repair, providing greater understanding of the brain as a whole and supporting the hypothesis that saving neurons alone
may not be sufficient [8]. This concept of a “neurovascular unit” defines tissue
remodeling as a highly dynamic process between vascular, neuronal, and glial cells.
After stroke, these cells respond to injury in a coordinated and synergistic manner,
releasing molecular signals and trophic factors that mutually influence each other to
create a pro-repair environment where tissue regeneration and neurological recovery may take place [32]. In recent years, the promotion of vascular growth and
remodeling in the injured brain is increasingly recognized as a particularly promising approach to treat brain illnesses [9]. This approach has brought confidence that
stimulating the growth of new vessels both in and around the ischemic site may
stabilize brain perfusion and promote tissue repair through neuronal survival, plasticity, and functional recovery [13, 14, 18].
7.3 Spatiotemporal Dynamic of Brain Angiogenesis
At the core of an ischemic incident, the severe energy and glucose loss induces a
rapid neuronal death, leaving behind a necrotic site within minutes after the stroke
onset. However, the surrounding area, called penumbra, has a mild-to-moderate
vascular compromise, where the energy deficit is less severe and collateral vessels
maintain a certain degree of blood flow (Fig. 7.1).
This area may be rescued if blood flow is restored [10]. Increasing evidence, in
both human stroke patients and animal experimental models, suggests that angiogenesis occurs in those penumbra areas [28]. Indeed, an increasing body of evidence
L. R. Nih et al.