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Developing Inner Ear Organoids in Ultrasound-Activated Piezoelectric Hydrogel for Assessing Ototoxicity
Yue Zhi1, Hui Zhang2, Jingjing Gan2
1Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China.
Researchers developed functional inner ear organoids (IEOs) using piezoelectric hydrogels and electrical stimulation. This innovative model effectively screens drugs for hearing loss and balance disorders, mitigating cisplatin-induced ototoxicity.
Area of Science:
- Biotechnology
- Regenerative Medicine
- Neuroscience
Background:
- Organoids are valuable for drug evaluation but their use in differentiating inner ear organoids (IEOs) for hearing and balance dysfunction is underexplored.
- Developing functional IEOs is crucial for identifying drug candidates targeting ototoxicity and neuropathy.
Purpose of the Study:
- To present a novel method for directed self-organization and differentiation of human induced pluripotent stem cells into IEOs.
- To investigate the potential of piezoelectric stimulation for enhancing auditory neuron development within IEOs.
- To establish a drug screening platform for ototoxicity and neuropathy using bioengineered IEOs.
Main Methods:
- Directed self-organization of human induced pluripotent stem cells within barium titanate-doped GelMA hydrogel.
- Utilizing the hydrogel's piezoelectric potential for electrical stimulation via ultrasonics to promote neuronal differentiation.
- Culturing and characterizing bioengineered IEOs, including hair cells and sensory neurons.
- Drug testing using resveratrol to assess mitigation of cisplatin-induced toxicity in IEOs.
Main Results:
- Successfully generated IEOs with highly differentiated auditory neurons and functional hair cells and sensory neurons.
- Electrical stimulation via piezoelectric hydrogel accelerated auditory neuron differentiation and maturation.
- The IEO model demonstrated resveratrol's efficacy in protecting against cisplatin-induced hair cell and sensory neuron toxicity.
- Established a functional drug screening system for ototoxicity and neuropathy.
Conclusions:
- The electrical stimulation-based approach using piezoelectric hydrogels offers a promising platform for creating reliable and functional IEOs.
- Bioengineered IEOs serve as an innovative drug screening system for preventing cisplatin-induced ototoxicity and neuropathy.
- This model advances the development of therapeutic strategies for hearing and balance disorders.
