The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment.

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Background Human brain models and pharmacological models of brain diseases are in high demand for drug screening because animal models have been found to be less than ideal for fully representing the human brain and are likely to fail during drug screening and testing; therefore, the construction of brain-like tissues is necessary. Due to the complexity of cortical tissue, the in vitro construction of brain-like tissue models has been restricted to mostly two-dimensional (2D) models and, on a limited scale, three-dimensional (3D) models. Methods In this study, 3D tissue blocks encapsulating neurons and astrocytes were constructed and cultured in vitro to mimic the cortex of the brain and to investigate the effects of astrocytes on the growth of neurons in a 3D culture. Results The results indicated that such methodology can provide a 3D culture environment suitable for neurons and astrocytes to live and function. When both cells were evenly mixed and cultured in a 3D manner, the astrocytes, which showed better outgrowth and a higher proliferation rate, benefited more than the neurons. On the other hand, the neurons benefited, showing longer axons and a denser network of dendrites, when they were accompanied by astrocytes at a certain distance. Conclusion In conclusion, astrocytes stimulated the outgrowth of neurons in a 3D culture environment in vitro. Regardless, the spatial relationship between both types of cells should be controlled. Thus, culturing cells in a 3D manner is necessary to investigate the correlations between them. This study provides a foundation for biofabricating 3D neurons’ cultures to allow for a deeper insight into the relationship between astrocytes or other glial cells and neurons in a 3D culture that is similar to the natural environment of the brain.

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Tissue-engineered cartilage (TEC) remains a potential alternative for the repair of articular cartilage defects. However, there has been a significant different between the properties of TEC and those of natural cartilage. Studies have shown that mechanical stimulation such as compressive load can help regulate matrix remodelling in TEC, thus affecting its biomechanical properties. However, the influences of shear induced from the tissue fluid phase have not been well studied and may play an important role in tissue regeneration especially when integrated with the compressive load. Therefore, the aim of this study was to quantitatively investigate the effects of combined loading mechanisms on TEC in vitro. A bespoke biosimulator was built to incorporate the coupled motion of compression, friction and shear. The specimens, encapsulating freshly isolated rabbit chondrocytes in a hydrogel, were cultured within the biosimulator under various mechanical stimulations for 4 weeks, and the tissue activity, matrix contents and the mechanical properties were examined. Study groups were categorized according to different mechanical stimulation combinations, including strain (5-20% at 5% intervals) and frequency (0.25 Hz, 0.5 Hz, 1 Hz), and the effects on tissue behaviour were investigated. During the dynamic culture process, a combined load was applied to simulate the combined effects of compression, friction and shear on articular cartilage during human movement. The results indicated that a larger strain and higher frequency were more favourable for the specimen in terms of the cell proliferation and extracellular matrix synthesis. Moreover, the combined mechanical stimulation was more beneficial to matrix remodelling than the single loading motion. However, the contribution of the combined mechanical stimulation to the engineered cartilaginous tissue matrix was not sufficient to impede biodegradation of the tissue with culture time.