A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts
Functional recovery in penetrating neurological injury is hampered by a lack of clinical regenerative therapies. Biomaterial therapies show promise as medical materials for neural repair through immunomodulation, structural support, and delivery of therapeutic biomolecules. However, a lack of facile...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2025-12-01
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| Series: | Neural Regeneration Research |
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| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-24-00422 |
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| author | Jessica Wiseman Raja Haseeb Basit Akihiro Suto Sagnik Middya Bushra Kabiri Michael Evans Vinoj George Christopher Adams George Malliaras Divya Maitreyi Chari |
| author_facet | Jessica Wiseman Raja Haseeb Basit Akihiro Suto Sagnik Middya Bushra Kabiri Michael Evans Vinoj George Christopher Adams George Malliaras Divya Maitreyi Chari |
| author_sort | Jessica Wiseman |
| collection | DOAJ |
| description | Functional recovery in penetrating neurological injury is hampered by a lack of clinical regenerative therapies. Biomaterial therapies show promise as medical materials for neural repair through immunomodulation, structural support, and delivery of therapeutic biomolecules. However, a lack of facile and pathology-mimetic models for therapeutic testing is a bottleneck in neural tissue engineering research. We have deployed a two-dimensional, high-density multicellular cortical brain sheet to develop a facile model of injury (macrotransection/scratch wound) in vitro. The model encompasses the major neural cell types involved in pathological responses post-injury. Critically, we observed hallmark pathological responses in injury foci including cell scarring, immune cell infiltration, precursor cell migration, and short-range axonal sprouting. Delivering test magnetic particles to evaluate the potential of the model for biomaterial screening shows a high uptake of introduced magnetic particles by injury-activated immune cells, mimicking in vivo findings. Finally, we proved it is feasible to create reproducible traumatic injuries in the brain sheet (in multielectrode array devices in situ) characterized by focal loss of electrical spiking in injury sites, offering the potential for longer term, electrophysiology plus histology assays. To our knowledge, this is the first in vitro simulation of transecting injury in a two-dimensional multicellular cortical brain cell sheet, that allows for combined histological and electrophysiological readouts of damage/repair. The patho-mimicry and adaptability of this simplified model of brain injury could benefit the testing of biomaterial therapeutics in regenerative neurology, with the option for functional electrophysiological readouts. |
| format | Article |
| id | doaj-art-59828f13b0524a20a5e9d029ae0c83fe |
| institution | Kabale University |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-59828f13b0524a20a5e9d029ae0c83fe2025-02-06T09:58:39ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-12-0120123539355210.4103/NRR.NRR-D-24-00422A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readoutsJessica WisemanRaja Haseeb BasitAkihiro SutoSagnik MiddyaBushra KabiriMichael EvansVinoj GeorgeChristopher AdamsGeorge MalliarasDivya Maitreyi ChariFunctional recovery in penetrating neurological injury is hampered by a lack of clinical regenerative therapies. Biomaterial therapies show promise as medical materials for neural repair through immunomodulation, structural support, and delivery of therapeutic biomolecules. However, a lack of facile and pathology-mimetic models for therapeutic testing is a bottleneck in neural tissue engineering research. We have deployed a two-dimensional, high-density multicellular cortical brain sheet to develop a facile model of injury (macrotransection/scratch wound) in vitro. The model encompasses the major neural cell types involved in pathological responses post-injury. Critically, we observed hallmark pathological responses in injury foci including cell scarring, immune cell infiltration, precursor cell migration, and short-range axonal sprouting. Delivering test magnetic particles to evaluate the potential of the model for biomaterial screening shows a high uptake of introduced magnetic particles by injury-activated immune cells, mimicking in vivo findings. Finally, we proved it is feasible to create reproducible traumatic injuries in the brain sheet (in multielectrode array devices in situ) characterized by focal loss of electrical spiking in injury sites, offering the potential for longer term, electrophysiology plus histology assays. To our knowledge, this is the first in vitro simulation of transecting injury in a two-dimensional multicellular cortical brain cell sheet, that allows for combined histological and electrophysiological readouts of damage/repair. The patho-mimicry and adaptability of this simplified model of brain injury could benefit the testing of biomaterial therapeutics in regenerative neurology, with the option for functional electrophysiological readouts.https://journals.lww.com/10.4103/NRR.NRR-D-24-00422in vitro modellingmultielectrode array interfacingnanoparticlesneuromaterialsscratch assaytransecting injurytraumatic brain injury |
| spellingShingle | Jessica Wiseman Raja Haseeb Basit Akihiro Suto Sagnik Middya Bushra Kabiri Michael Evans Vinoj George Christopher Adams George Malliaras Divya Maitreyi Chari A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts Neural Regeneration Research in vitro modelling multielectrode array interfacing nanoparticles neuromaterials scratch assay transecting injury traumatic brain injury |
| title | A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts |
| title_full | A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts |
| title_fullStr | A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts |
| title_full_unstemmed | A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts |
| title_short | A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts |
| title_sort | macro transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts |
| topic | in vitro modelling multielectrode array interfacing nanoparticles neuromaterials scratch assay transecting injury traumatic brain injury |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-24-00422 |
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