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Linkedin biotis-bordeaux

Secretary Email

33 (0)5 57 57 14 88

Bioingénierie Tissulaire (BioTis)

Physical Address:

Batiment BBS (Bordeaux Biologie Santé), 5e étage

2, rue du Dr Hoffmann Martinot,

33000, Bordeaux, France

Mailing Address:

Université de Bordeaux, Campus Carreire

146, rue Léo Saignat, Case 84,

33076, Bordeaux Cedex, France

Development of an Innovative Medical Device for Laser-Assisted Drug Delivery (LADD)

Abstract

Reference

Project Leader

According to the World Health Organization, 430 million people worldwide currently experience disabling hearing loss, about 5% of the global population, and this number is expected to surpass 700 million by 2050 (1). Most congenital and early-onset hearing losses are of genetic origin (2), and many are not amenable to conventional pharmacotherapy. Gene therapy has therefore emerged as a promising approach, with proof-of-concept studies demonstrating hearing restoration in mouse models carrying Otof (DFNB9) or Clrn1 (Usher syndrome type IIIA) mutations (3,4).

▷World Health Organization. Deafness and Hearing Loss. https://www.who.int/news-room/fact-sheets/detail/deafness-and-hearing-loss (2025).

▷Smith, R. J. H., Bale, J. F. & White, K. R. Sensorineural hearing loss in children. Lancet 365, 879–890 (2005).

▷Akil, O. et al. Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model. Proc Natl Acad Sci U S A 116, 4496–4501 (2019).

▷Dulon, D. et al. Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome. J Clin Invest 128, 3382–3401 (2018).

▷Lv, J. et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. Lancet 403, 2317–2325 (2024).

▷Liu, S. S. & Yang, R. Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities. Front Neurosci 16, 867453 (2022).

▷Piu, F. et al. OTO-104: a sustained-release dexamethasone hydrogel for the treatment of otic disorders. Otol Neurotol 32, 171–179 (2011).

▷Glueckert, R. et al. Anatomical basis of drug delivery to the inner ear. Hear Res 368, 10–27 (2018).

▷Jaffredo, M. et al. Proof of concept of intracochlear drug administration by laser-assisted bioprinting in mice. Hear Res 438, 108880 (2023).

Raphaël Devillard

Olivia Kérourédan

In Otof knock-out mice, a single intracochlear injection of recombinant AAV2-Otof restores otoferlin expression and rescues hearing (3), while Clrn1 supplementation prevents progressive auditory decline in inducible KO models (4). Recent clinical trial data in DFNB9 patients further support the translational potential of AAV-based therapies (5). However, delivering therapeutic vectors safely and precisely to the inner ear remains a major challenge. Transtympanic injections are minimally invasive but result in uncontrolled diffusion, low intracochlear bioavailability, and off-target spread. Intracochlear injections improve dosing accuracy but are invasive, operator-dependent, and carry risks of trauma, fibrosis, and long-term cochlear damage (6,7). The cochlea’s anatomy, including the blood–labyrinth barrier and limited accessibility of the round window membrane (RWM), further complicates targeted delivery (8). To address these limitations, our team has developed an innovative Laser-Assisted Drug Delivery (LADD) device inspired by Laser-Assisted Bioprinting. Using a nanosecond fiber laser, the system generates a controlled jet that deposits therapeutic agents directly onto the RWM with micrometric precision, without perforation or invasive access (9).

The device aims to:

i/ improve the accuracy and reproducibility of RWM deposition;

ii/ enable localized delivery of corticosteroids, nanoparticles, or viral vectors (AAV);

iii/ provide a platform for future cochlear gene therapy.

Preclinical studies show safe laser parameters, preserved auditory function, and effective dexamethasone diffusion, supporting further development toward clinical translation.

Bedoux Agathe

Collaborator