Impact of microchannel width on axons for brain-on-chip applications.

Technologies for axon guidance for in vitro disease models and bottom up investigations are increasingly being used in neuroscience research. One of the most prevalent patterning methods is using polydimethylsiloxane (PDMS) microstructures due to compatibility with microscopy and electrophysiology which enables systematic tracking of axon development with precision and efficiency. Previous investigations of these guidance platforms have noted axons tend to follow edges and avoid sharp turns; however, the specific impact of spatial constraints remains only partially explored. We investigated the influence of microchannel width beyond a constriction point, as well as the number of available microchannels, on axon growth dynamics. Further, by manipulating the size of micron/submicron-sized PDMS tunnels we investigated the space restriction that prevents growth cone penetration showing that restrictions smaller than 350 nm were sufficient to exclude axons. This research offers insights into the interplay of spatial constraints, axon development, and neural behavior. The findings are important for designing in vitro platforms and in vivo neural interfaces for both fundamental neuroscience and translational applications in rapidly evolving neural implant technologies.

Photopatterning of conductive hydrogels which exhibit tissue-like properties.

Hydrogels are three-dimensional, highly tunable material systems that can match the properties of extracellular matrices. In addition to being widely used to grow and modulate cell behavior, hydrogels can be made conductive to further modulate electrically active cells, such as neurons, and even incorporated into multielectrode arrays to interface with tissues. To enable conductive hydrogels, graphene flakes can be mechanically suspended into a hydrogel precursor. The conductivity of the hydrogel can be increased by increasing the weight percentage of graphene flakes in the precursor while maintaining the mechanical properties of the formed gel similar to the properties of neural tissue. By using a photocrosslinkable hydrogel matrix, such as gelatin methacrylate, with a photoabsorber, the conductive precursor solutions can be crosslinked into predefined complex patterns. Finally, the formulations can be used to support the growth of sensory neurons, derived from human induced pluripotent stem cells, for more than 7 weeks while the neurons remain viable. These scaffolds can be patterned into components of multielectrode arrays, to enable ultrasoft electrodes with tissue-matched properties for further interactions, both in vitro and in vivo, with the nervous systems.

Engineering an in vitro retinothalamic nerve model.

Understanding the retinogeniculate pathway in vitro can offer insights into its development and potential for future therapeutic applications. This study presents a Polydimethylsiloxane-based two-chamber system with axon guidance channels, designed to replicate unidirectional retinogeniculate signal transmission in vitro. Using embryonic rat retinas, we developed a model where retinal spheroids innervate thalamic targets through up to 6 mm long microfluidic channels. Using a combination of electrical stimulation and functional calcium imaging we assessed how channel length and electrical stimulation frequency affects thalamic target response. In the presented model we integrated up to 20 identical functional retinothalamic neural networks aligned on a single transparent microelectrode array, enhancing the robustness and quality of recorded functional data. We found that network integrity depends on channel length, with 0.5-2 mm channels maintaining over 90% morphological and 50% functional integrity. A reduced network integrity was recorded in longer channels. The results indicate a notable reduction in forward spike propagation in channels longer than 4 mm. Additionally, spike conduction fidelity decreased with increasing channel length. Yet, stimulation-induced thalamic target activity remained unaffected by channel length. Finally, the study found that a sustained thalamic calcium response could be elicited with stimulation frequencies up to 31 Hz, with higher frequencies leading to transient responses. In conclusion, this study presents a high-throughput platform that demonstrates how channel length affects retina to brain network formation and signal transmission in vitro.

Gamification of Physical Therapy Exercises Using Commercial Entertainment Content: A Safety and Feasibility Study.

Independent physiotherapy at home is a crucial element of rehabilitative care for a wide range of conditions as it constitutes a large portion of the overall therapy dose. However, up to 80% of individuals who are prescribed at-home physiotherapy do not consistently adhere to their treatment schedule, resulting in poor treatment outcomes. This is likely due to a lack of motivation and progress tracking in the current standard of care. We have developed a novel software prototype that allows users to control commercial entertainment content, such as video games or interactive music videos, with their movements during physiotherapy. By connecting therapy to proven entertainment content, we aim to improve on the current motivational deficits. This study investigated the safety and feasibility of this concept in a controlled environment over four physical therapy sessions with seven patients suffering from musculoskeletal and neurological conditions. As a secondary outcome, patients were asked about their enjoyment, perceived competence and effort using the Intrinsic Motivation Inventory (IMI) questionnaire. All participants were able to interact with the presented entertainment content and completed the study with no adverse events. Despite the diversity in pathology, age and training scenarios, the entertainment content maintained the patients' enjoyment with a high average rate of 6/7 on the IMI scale. Interacting with commercial entertainment content by doing physical therapy exercises was feasible, safe, and well-received over the six-week study period.