Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study
Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulat...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7031 |
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| author | Zhuo-Hao Liu Yin-Cheng Huang Chang-Yi Kuo Chao-Ying Kuo Chieh-Yu Chin Ping K. Yip Jyh-Ping Chen |
| author_facet | Zhuo-Hao Liu Yin-Cheng Huang Chang-Yi Kuo Chao-Ying Kuo Chieh-Yu Chin Ping K. Yip Jyh-Ping Chen |
| author_sort | Zhuo-Hao Liu |
| collection | DOAJ |
| description | Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 μM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI. |
| first_indexed | 2024-03-10T16:05:15Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:05:15Z |
| publishDate | 2020-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0113856672d54a909d15591da1f0d63a2023-11-20T14:56:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119703110.3390/ijms21197031Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo StudyZhuo-Hao Liu0Yin-Cheng Huang1Chang-Yi Kuo2Chao-Ying Kuo3Chieh-Yu Chin4Ping K. Yip5Jyh-Ping Chen6Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University School of Medicine, Kwei-San, Taoyuan 33305, TaiwanDepartment of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University School of Medicine, Kwei-San, Taoyuan 33305, TaiwanDepartment of Chemical and Materials and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanDepartment of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University School of Medicine, Kwei-San, Taoyuan 33305, TaiwanDepartment of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University School of Medicine, Kwei-San, Taoyuan 33305, TaiwanQueen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Neuroscience, Surgery & Trauma, London E1 2AT, UKDepartment of Chemical and Materials and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanSpinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 μM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI.https://www.mdpi.com/1422-0067/21/19/7031nanofiberspinal cord injurydocosahexaenoic acidregenerative medicinepoly(lactic acid) |
| spellingShingle | Zhuo-Hao Liu Yin-Cheng Huang Chang-Yi Kuo Chao-Ying Kuo Chieh-Yu Chin Ping K. Yip Jyh-Ping Chen Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study International Journal of Molecular Sciences nanofiber spinal cord injury docosahexaenoic acid regenerative medicine poly(lactic acid) |
| title | Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study |
| title_full | Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study |
| title_fullStr | Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study |
| title_full_unstemmed | Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study |
| title_short | Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study |
| title_sort | docosahexaenoic acid loaded polylactic acid core shell nanofiber membranes for regenerative medicine after spinal cord injury in vitro and in vivo study |
| topic | nanofiber spinal cord injury docosahexaenoic acid regenerative medicine poly(lactic acid) |
| url | https://www.mdpi.com/1422-0067/21/19/7031 |
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