Proof of concept of intracochlear drug administration by laser-assisted bioprinting in mice

• Published in: Hearing research 2023-10, Vol.438, p.108880-108880, Article 108880
• Main Authors: Jaffredo, Manon, Duchamp, Océane, Touya, Nicolas, Bouleau, Yohan, Dulon, Didier, Devillard, Raphael, Bonnard, Damien
• Format: Article
• Language: English
• Subjects: Drug delivery; Hearing loss; Inner ear; Laser-assisted bioprinting
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2023.108880

•Intracochlear drug delivery is a major challenge for future application in humans.•Laser-assisted bioprinting enables precise dexamethasone deposit on the round window membrane.•Round window bioprinting allows intracochlear dexamethasone diffusion in the perilymph, without auditory impairment. Transtympanic administration is used clinically for the injection of gentamicin and/or corticosteroids. This atraumatic route is based on passive diffusion through the round window membrane (RWM). The main limitation of this method is related to the clearance through the Eustachian tube, making the concentration of the therapeutic agent at the intracochlear level uncertain and limited. Moreover, this technique remains unsuitable for molecules of high molecular weight or in the case of gene therapies. The purpose was to study a new technique of intracochlear administration in an atraumatic, direct and controlled manner by laser-assisted bioprinting (LAB). LAB was used to deliver dexamethasone phosphate with thermosensitive hydrogel on the mouse RWM. After validation of the regularity and homogeneity of the pattern, the diffusion in vivo of the dexamethasone into the perilymph after LAB has been confirmed by ELISA. Auditory function measurements showed no hearing impairment suggesting that bioprinting does not induce significant cochlear damage. Hence, the present proof of concept study introduces a promising approach for inner ear drug delivery. [Display omitted]