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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].

▷[1] World Health Organization. Deafness and Hearing Loss. https://www.who.int/news-room/fact-sheets/detail/deafness-and-hearing-loss (2025).

▷[2] Smith, R. J. H., Bale, J. F. & White, K. R. Sensorineural hearing loss in children. Lancet 365, 879–890 (2005).

▷[3] 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).

▷[4] Dulon, D. et al. Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome. J Clin Invest 128, 3382–3401 (2018).

▷[5] Lv, J. et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. Lancet 403, 2317–2325 (2024).

▷[6] Liu, S. S. & Yang, R. Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities. Front Neurosci 16, 867453 (2022).

▷[7] Piu, F. et al. OTO-104: a sustained-release dexamethasone hydrogel for the treatment of otic disorders. Otol Neurotol 32, 171–179 (2011).

▷[8] Glueckert, R. et al. Anatomical basis of drug delivery to the inner ear. Hear Res 368, 10–27 (2018).

▷[9] Jaffredo, M. et al. Proof of concept of intracochlear drug administration by laser-assisted bioprinting in mice. Hear Res 438, 108880 (2023).

Raphaël Devillard

Dr. 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