Novel dual-lumen microneedle delivers adeno-associated viral vectors in the guinea pig inner ear via the round window membrane.
The clinical need for minimally invasive inner ear diagnostics and therapeutics has grown rapidly in recent years, particularly with the development of gene therapies for treating hearing and balance disorders. These therapies often require delivery of large injectate volumes that can cause hearing...
| Publicado en: | Biomedical Microdevices Vol. 27; no. 2; pp. 1 - 19 |
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| Autores principales: | , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jun2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=185850200&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 185850200 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 13872176 ODN jtl: Biomedical Microdevices issn: 13872176 maglogo: N pubinfo: dt: Jun2025 vid: 27 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 185850200 10.1007/s10544-025-00751-4 185850200 ppf: 1 ppct: 18 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Novel dual-lumen microneedle delivers adeno-associated viral vectors in the guinea pig inner ear via the round window membrane. aug: au: Hammer, Daniella R. Voruz, François Aksit, Aykut Breil, Eugénie Rousset, Francis Senn, Pascal Ilmjärv, Sten Olson, Elizabeth S. Lalwani, Anil K. Kysar, Jeffrey W. affil: https://ror.org/00hj8s172 Department of Mechanical Engineering, Columbia University, 10027, New York, NY, USA sug: ab: The clinical need for minimally invasive inner ear diagnostics and therapeutics has grown rapidly in recent years, particularly with the development of gene therapies for treating hearing and balance disorders. These therapies often require delivery of large injectate volumes that can cause hearing damage. In response to this challenge, dual-lumen microneedles, with two separate fluidic pathways controlled independently by micropumps, were designed for simultaneous aspiration and delivery to the inner ear across the round window membrane (RWM) and were fabricated using 2-photon polymerization (2PP). To assess the proof of concept of the dual-lumen microneedle device, simultaneous injection of 5 µL of adeno-associated virus (AAV) expressing green fluorescent protein (GFP) and aspiration of 5 µL of perilymph was performed in guinea pigs in vivo. Hearing thresholds were measured using auditory brainstem response (ABR) at time points before and 1 week after the procedure. Confocal imaging of the cochlea, the utricle, and the contralateral inner ear was employed to quantify and characterize the spatial distribution of hair cells with AAV transduction. Dual-lumen microneedle devices were found to be functional in the surgical setting. There was hearing loss limited to higher frequencies of 24 kHz and 28 kHz with ABR mean threshold shifts of 13 dB sound pressure level (SPL) (p = 0.03) and 23 dB SPL (p < 0.01), respectively. Furthermore, cochlear AAV transduction with a stereotypical basoapical gradient was observed in all animals (n = 5). Thus, dual-lumen microneedles can facilitate delivery of large volumes of therapeutic material into the inner ear, overcoming the limitations of single-lumen microneedles. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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