Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord
Biomaterials are being developed as therapeutics for spinal cord injury (SCI) that can stabilize and bridge acute lesions and mediate the delivery of transgenes, providing a localized and sustained reservoir of regenerative factors. For clinical use, direct injection of biomaterial scaffolds is pref...
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2021-03-01
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Series: | APL Bioengineering |
Online Access: | http://dx.doi.org/10.1063/5.0035291 |
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doaj-22347fddcd3e4649b5ee54ed2b0248bc2021-04-02T15:43:59ZengAIP Publishing LLCAPL Bioengineering2473-28772021-03-0151016104016104-1810.1063/5.0035291Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cordArshia Ehsanipour0Mayilone Sathialingam1Laila M. Rad2Joseph de Rutte3Rebecca D. Bierman4Jesse Liang5Weikun Xiao6Dino Di Carlo7Stephanie K. Seidlits8 Department of Bioengineering, University of California, Los Angeles, California 90095, USA Department of Bioengineering, University of California, Los Angeles, California 90095, USA Department of Bioengineering, University of California, Los Angeles, California 90095, USA Department of Bioengineering, University of California, Los Angeles, California 90095, USA Department of Bioengineering, University of California, Los Angeles, California 90095, USA Department of Bioengineering, University of California, Los Angeles, California 90095, USA Department of Bioengineering, University of California, Los Angeles, California 90095, USA Department of Bioengineering, University of California, Los Angeles, California 90095, USA Department of Bioengineering, University of California, Los Angeles, California 90095, USABiomaterials are being developed as therapeutics for spinal cord injury (SCI) that can stabilize and bridge acute lesions and mediate the delivery of transgenes, providing a localized and sustained reservoir of regenerative factors. For clinical use, direct injection of biomaterial scaffolds is preferred to enable conformation to unique lesions and minimize tissue damage. While an interconnected network of cell-sized macropores is necessary for rapid host cell infiltration into—and thus integration of host tissue with—implanted scaffolds, injectable biomaterials have generally suffered from a lack of control over the macrostructure. As genetic vectors have short lifetimes in vivo, rapid host cell infiltration into scaffolds is a prerequisite for efficient biomaterial-mediated delivery of transgenes. We present scaffolds that can be injected and assembled in situ from hyaluronic acid (HA)-based, spherical microparticles to form scaffolds with a network of macropores (∼10 μm). The results demonstrate that addition of regularly sized macropores to traditional hydrogel scaffolds, which have nanopores (∼10 nm), significantly increases the expression of locally delivered transgene to the spinal cord after a thoracic injury. Maximal cell and axon infiltration into scaffolds was observed in scaffolds with more regularly sized macropores. The delivery of lentiviral vectors encoding the brain-derived neurotrophic factor (BDNF), but not neurotrophin-3, from these scaffolds further increased total numbers and myelination of infiltrating axons. Modest improvements to the hindlimb function were observed with BDNF delivery. The results demonstrate the utility of macroporous and injectable HA scaffolds as a platform for localized gene therapies after SCI.http://dx.doi.org/10.1063/5.0035291 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arshia Ehsanipour Mayilone Sathialingam Laila M. Rad Joseph de Rutte Rebecca D. Bierman Jesse Liang Weikun Xiao Dino Di Carlo Stephanie K. Seidlits |
spellingShingle |
Arshia Ehsanipour Mayilone Sathialingam Laila M. Rad Joseph de Rutte Rebecca D. Bierman Jesse Liang Weikun Xiao Dino Di Carlo Stephanie K. Seidlits Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord APL Bioengineering |
author_facet |
Arshia Ehsanipour Mayilone Sathialingam Laila M. Rad Joseph de Rutte Rebecca D. Bierman Jesse Liang Weikun Xiao Dino Di Carlo Stephanie K. Seidlits |
author_sort |
Arshia Ehsanipour |
title |
Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord |
title_short |
Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord |
title_full |
Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord |
title_fullStr |
Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord |
title_full_unstemmed |
Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord |
title_sort |
injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord |
publisher |
AIP Publishing LLC |
series |
APL Bioengineering |
issn |
2473-2877 |
publishDate |
2021-03-01 |
description |
Biomaterials are being developed as therapeutics for spinal cord injury (SCI) that can stabilize and bridge acute lesions and mediate the delivery of transgenes, providing a localized and sustained reservoir of regenerative factors. For clinical use, direct injection of biomaterial scaffolds is preferred to enable conformation to unique lesions and minimize tissue damage. While an interconnected network of cell-sized macropores is necessary for rapid host cell infiltration into—and thus integration of host tissue with—implanted scaffolds, injectable biomaterials have generally suffered from a lack of control over the macrostructure. As genetic vectors have short lifetimes in vivo, rapid host cell infiltration into scaffolds is a prerequisite for efficient biomaterial-mediated delivery of transgenes. We present scaffolds that can be injected and assembled in situ from hyaluronic acid (HA)-based, spherical microparticles to form scaffolds with a network of macropores (∼10 μm). The results demonstrate that addition of regularly sized macropores to traditional hydrogel scaffolds, which have nanopores (∼10 nm), significantly increases the expression of locally delivered transgene to the spinal cord after a thoracic injury. Maximal cell and axon infiltration into scaffolds was observed in scaffolds with more regularly sized macropores. The delivery of lentiviral vectors encoding the brain-derived neurotrophic factor (BDNF), but not neurotrophin-3, from these scaffolds further increased total numbers and myelination of infiltrating axons. Modest improvements to the hindlimb function were observed with BDNF delivery. The results demonstrate the utility of macroporous and injectable HA scaffolds as a platform for localized gene therapies after SCI. |
url |
http://dx.doi.org/10.1063/5.0035291 |
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