Background Inner ear is crucial for maintaining normal functions of human sensory perception. However, current perceptual reconstruction is mostly limited to symptomatic relief and lacks a radical cure for irreversible damage. The development of new strategies for the fundamental treatment of inner ear diseases has become a major challenge in the biomedical field. Inner ear organoids are an emerging platform for researching inner ear diseases. This is due to their highly biomimetic properties, personalization potential, high-throughput screening capabilities and standardized production. Constructing biomimetic inner ear organoids is vital for understanding physiological mechanisms and developing new therapies. However, current approaches to inner ear organoid construction lack morphological fidelity. Consequently, hair cells (HCs) and spiral ganglion neurons (SGNs) remain functionally immature and fail to accurately recapitulate normal inner ear physiology. It is urgent to explore the strategies for constructing highly bionic inner ear organoids. Technology Advanced 3D bioprinting technology has the potential to enable the construction of high-fidelity inner ear organoids. Against to the existing approaches, 3D bioprinting achieves high-fidelity construction of inner ear organoids through precision spatial assembly of cell-laden bioinks. Results This article explores the link between 3D bioprinting and inner ear organoid construction. A 3D bioprinting strategy for the construction of inner ear organoid was proposed. Thereafter, the future applications of 3D bioprinted inner ear organoid are envisioned. Eventually, the challenges and opportunities of using 3D bioprinting to build inner ear organoids were discussed.
Ageing plays a pivotal role in spinal cord (SC)-related disorders, but the impact of ageing on the SC, especially with respect to its material properties, remains poorly understood. Prior investigations have primarily focused on static uniaxial testing, leaving dynamic mechanical assessment significantly unexplored. Addressing this research deficit, this investigation delivers an extensive examination of mechanical and viscoelastic characteristics in aged SC specimens utilizing rat models. Essential measurements encompassing elasticity and viscoelasticity, specifically peak force, moduli, and hysteresis, are documented. This investigation uniquely emphasizes the intricate aspects of aged tissue behavior, including frequency-dependent responses, non-linear properties, and conditioning phenomena. For the first time, this study emphasizes the complex characteristics of aged tissue response, such as frequency dependence, non-linearity, and conditioning effects. Furthermore, the influence of preconditioning and conditioning is examined, revealing regional dependencies. These results highlight the inadequacy of current models that assume isotropic, linear elasticity, and homogeneity in representing the SC. The findings establish fundamental material property data essential for subsequent research comparing normal and pathological SC mechanics, advancing computational modeling capabilities and deepening the comprehension of SC structure-function relationships.
The transdermal delivery of macromolecular drugs has long been limited by the barrier effect of the stratum corneum and the underlying active epidermis. A recent study published in Nature proposed a non-invasive transdermal delivery strategy based on poly[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate] (OP). This strategy takes advantage of the pH gradient from the acidic surface to the neutral deep layers of the skin to achieve efficient penetration of OP and OP-insulin through the stratum corneum, active epidermis, and dermis. OP-insulin possesses full-thickness skin permeability, enabling it to penetrate all skin layers and subsequently enter the systemic circulation. It also facilitates intratissue diffusion through membrane surface hopping and intercellular contact transfer. Experiments in mice and minipigs demonstrated that locally administered OP-insulin could rapidly enter the bloodstream and exhibited broad tissue distribution, as evidenced by fluorescence accumulation in organs such as the liver, fat, and muscle. This study showcases the potential of transdermal delivery strategies that combine material chemistry with the characteristics of the skin microenvironment for the non-invasive delivery of macromolecular drugs, offering new therapeutic approaches for diseases such as diabetes.
