Living scaffolds for neuroregeneration

Struzyna, Laura A.; Katiyar, Kritika S.; Cullen, D. Kacy

doi:10.1016/j.cossms.2014.07.004

Cited by 65 publications

(107 citation statements)

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“…Here, we are pursuing the creation of tissue engineered “living scaffolds” to facilitate nervous system regeneration [15–21]. Living scaffolds derive from a combination of biomaterial and cell-based techniques to create preformed constructs consisting of living cells in a defined, often anisotropic, three-dimensional (3-D) [15,16] architecture. Of note, the engineering of living constructs with defined 3-D cytoarchitecture is what differentiates this approach from more conventional “cell seeding” strategies.…”

Section: Introductionmentioning

confidence: 99%

Transplantable living scaffolds comprised of micro-tissue engineered aligned astrocyte networks to facilitate central nervous system regeneration

et al. 2016

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Neurotrauma, stroke, and neurodegenerative disease may result in widespread loss of neural cells as well as the complex interconnectivity necessary for proper central nervous system function, generally resulting in permanent functional deficits. Potential regenerative strategies involve the recruitment of endogenous neural stem cells and/or directed axonal regeneration through the use of tissue engineered “living scaffolds” built to mimic features of three-dimensional (3-D) in vivo migratory or guidance pathways. Accordingly, we devised a novel biomaterial encasement scheme using tubular hydrogel-collagen micro-columns that facilitated the self-assembly of seeded astrocytes into 3-D living scaffolds consisting of long, cable-like aligned astrocytic networks. Here, robust astrocyte alignment was achieved within a micro-column inner diameter (ID) of 180 μm or 300–350 μm but not 1.0 mm, suggesting that radius of curvature dictated the extent of alignment. Moreover, within small ID micro-columns, >70% of the astrocytes assumed a bi-polar morphology, versus ~10% in larger micro-columns or planar surfaces. Cell–cell interactions also influenced the aligned architecture, as extensive astrocyte-collagen contraction was achieved at high (9–12 × 105 cells/mL) but not lower (2–6 × 105 cells/mL) seeding densities. This high density micro-column seeding led to the formation of ultra-dense 3-D “bundles” of aligned bi-polar astrocytes within collagen measuring up to 150 μm in diameter yet extending to a remarkable length of over 2.5 cm. Importantly, co-seeded neurons extended neurites directly along the aligned astrocytic bundles, demonstrating permissive cues for neurite extension. These transplantable cable-like astrocytic networks structurally mimic the glial tube that guides neuronal progenitor migration in vivo along the rostral migratory stream, and therefore may be useful to guide progenitor cells to repopulate sites of widespread neurodegeneration. Statement of Significance This manuscript details our development of novel micro-tissue engineering techniques to generate robust networks of longitudinally aligned astrocytes within transplantable micro-column hydrogels. We report a novel biomaterial encasement scheme that facilitated the self-assembly of seeded astrocytes into long, aligned regenerative pathways. These miniature “living scaffold” constructs physically emulate the glial tube – a pathway in the brain consisting of aligned astrocytes that guide the migration of neuronal progenitor cells – and therefore may facilitate directed neuronal migration for central nervous system repair. The small size and self-contained design of these aligned astrocyte constructs will permit minimally invasive transplantation in models of central nervous system injury in future studies.

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Section: Introductionmentioning

confidence: 99%

Transplantable living scaffolds comprised of micro-tissue engineered aligned astrocyte networks to facilitate central nervous system regeneration

et al. 2016

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“…Hepatocyte growth factor containing microspheres also increased neuroblast migration from the SVZ to the strokeinjured tissue in the same model (Nakaguchi et al, 2012). FGF-2 in heparin-chitosan scaffolds demonstrates sustained survival and growth of NSC, where these multifunctional, biocompatible microspheres are optimized for NSC grafting (Struzyna et al, 2014). The use of stem cells and growth factors in conjunction with biocompatible and degradable scaffolds shows high potential to create a microenvironment that promotes functional recovery following injury.…”

Section: Considerations For Development Of An Ideal Scaffoldmentioning

confidence: 97%

Stroke Repair via Biomimicry of the Subventricular Zone

Matta

Gonzalez

2018

Front. Mater.

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Stroke is among the leading causes of death and disability worldwide, 85% of which are ischemic. Current stroke therapies are limited by a narrow effective therapeutic time and fail to effectively complete the recovery of the damaged area. Magnetic resonance imaging of the subventricular zone (SVZ) following infarct/stroke has allowed visualization of new axonal connections and projections being formed, while new immature neurons migrate from the SVZ to the peri-infarct area. Such studies suggest that the SVZ is a primary source of regenerative cells for the repair and regeneration of stroke-damaged neurons and tissue. Therefore, the development of tissue engineered scaffolds that serve as a bioreplicative SVZ niche would support the survival of multiple cell types that reside in the SVZ. Essential to replication of the human SVZ microenvironment is the establishment of microvasculature that regulates both the healthy and stroke-injured blood-brain barrier, which is dysregulated poststroke. In order to reproduce this niche, understanding how cells interact in this environment is critical, in particular neural stem cells, endothelial cells, pericytes, ependymal cells, and microglia. Remodeling and repair of the matrix-rich SVZ niche by endogenous reparative mechanisms may then support functional recovery when enhanced by an artificial niche that supports the survival and proliferation of migrating vascular and neuronal cells. Critical considerations to mimic this area include an understanding of resident cell types, delivery method, and the use of biocompatible materials. Controlling stem cell survival, differentiation, and migration are key factors to consider when transplanting stem cells. Here, we discuss the role of the SVZ architecture and resident cells in the promotion and enhancement of endogenous repair mechanisms. We elucidate the interplay between the extracellular matrix composition and cell interactions prior to and following stroke. Finally, we review current cell and neuronal niche biomimetic materials that allow for a tissue-engineered approach in order to promote structural and functional restoration of neural circuitry. By creating an artificial mimetic SVZ, tissue engineers can strive to facilitate tissue regeneration and functional recovery.

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“…The recent findings show that an ideal implant for peripheral nerve tissue regeneration (PNTR) should both physically and biochemically resemble properties of a peripheral nerve extracellular matrix. First of all, the NGC should be in the form of a semipermeable hydrogel membrane that incorporates haptotactic, chemotactic, and mechanical cues to spatiotemporally navigate the nerve cell outgrowth as well as ensures the avoidance of inappropriate connections (Struzyna et al, 2014). Recent studies have shown that nervous cells are also sensitive to topographical cues (Stoll et al, 2014).…”

Section: Introductionmentioning

confidence: 98%