Spatial Control of Mechanical Factors: a New Design Rationale for Nerve Tissue Engineering

Peripheral nerve injuries (PNI) result from traumatic injury, surgery or repetitive compression, and are reported in 3-5% of all trauma patients. The impact ranges from severe (major loss of sensory/motor function and/or intractable neuropathic pain) to mild (some sensory and/or motor deficits) and in both cases, is devastating for the patient. PNI affect ∼1M people in Europe and the US p.a. of whom 660,000 have surgery. PNI has high healthcare, unemployment, rehabilitation, societal costs and affects mostly young people. The current surgical practice for nerve gaps >3 cm is to bridge the site of injury with a graft taken from the patient. However, this involves additional time, cost and damage to a healthy nerve, limited supply, and unsatisfactory functional recovery (50% of the cases). For these reasons, research has focused on developing artificial nerve conduits to replace grafts, but to-date those available for clinical use do not match and/or exceed the functional performance of the autograft. This project develops a rational basis for promoting neurite growth through tissue-engineered conduits for peripheral nerve repair, by exploiting the response of cells to spatial variations in mechanical properties of conduits to inform their design. This is achieved through an interdisciplinary approach, that combines in vitro experimentation with mathematical modelling. First of all, the mechanical and structural properties of RAFTStabilised collagen gels (RsC) are explored, physiologically coherent RsC stiffness gradients are fabricated and characterised as well as the neuronal response to them. Finally, a predictive framework to inform the design of nerve conduits is parameterised and tested using experimental results and literature. The use of this multidisciplinary approach can help tissue engineers in the development of novel tissue repair solutions, as well as informing mathematical models of neurite behaviour which can contribute to the design process

Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons

Acknowledgements: This research was funded in whole, or in part, by the UKRI EPSRC Healthcare Technologies Challenge Award EP/N020987/1. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Additionally, the authors acknowledge James Fisk for machining the airtight box to contain the isoflurane and Risto Martin for his assistance with the syringe pump, vaporiser and compressed air noise damping table. The authors also acknowledge Dr. Jacob Seifert and Zuzana Coculova for their insight on the loss tangent.General anaesthetics are widely used for their analgesic, immobilising, and hypnotic effects. The mechanisms underlying these effects remain unclear, but likely arise from alterations to cell microstructure, and potentially mechanics. Here we investigate this hypothesis using a custom experimental setup combining calcium imaging and nanoindentation to quantify the firing activity and mechanical properties of dorsal root ganglion-derived neurons exposed to a clinical concentration of 1% isoflurane gas, a halogenated ether commonly used in general anaesthesia. We found that cell viscoelasticity and functional activity are simultaneously and dynamically altered by isoflurane at different stages of exposure. Particularly, cell firing count correlated linearly with the neuronal loss tangent, the ratio of mechanical energy dissipation and storage by the cell. Our results demonstrate that anaesthetics affect cells as a whole, reconciling seemingly contradictory theories of how anaesthetics operate, and highlight the importance of considering cell mechanics in neuronal functions, anaesthesia, and clinical neuroscience in general

Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons

AbstractGeneral anaesthetics are widely used for their analgesic, immobilising, and hypnotic effects. The mechanisms underlying these effects remain unclear, but likely arise from alterations to cell microstructure, and potentially mechanics. Here we investigate this hypothesis using a custom experimental setup combining calcium imaging and nanoindentation to quantify the firing activity and mechanical properties of dorsal root ganglion-derived neurons exposed to a clinical concentration of 1% isoflurane gas, a halogenated ether commonly used in general anaesthesia. We found that cell viscoelasticity and functional activity are simultaneously and dynamically altered by isoflurane at different stages of exposure. Particularly, cell firing count correlated linearly with the neuronal loss tangent, the ratio of mechanical energy dissipation and storage by the cell. Our results demonstrate that anaesthetics affect cells as a whole, reconciling seemingly contradictory theories of how anaesthetics operate, and highlight the importance of considering cell mechanics in neuronal functions, anaesthesia, and clinical neuroscience in general.</jats:p

Predator crown-of-thorns starfish (Acanthaster planci) outbreak, mass mortality of corals, and cascading effects on reef fish and benthic communities

Outbreaks of the coral-killing seastar Acanthaster planci are intense disturbances that can decimate coral reefs. These events consist of the emergence of large swarms of the predatory seastar that feed on reef-building corals, often leading to widespread devastation of coral populations. While cyclic occurrences of such outbreaks are reported from many tropical reefs throughout the Indo-Pacific, their causes are hotly debated, and the spatio-temporal dynamics of the outbreaks and impacts to reef communities remain unclear. Based on observations of a recent event around the island of Moorea, French Polynesia, we show that Acanthaster outbreaks are methodic, slow-paced, and diffusive biological disturbances. Acanthaster outbreaks on insular reef systems like Moorea's appear to originate from restricted areas confined to the ocean-exposed base of reefs. Elevated Acanthaster densities then progressively spread to adjacent and shallower locations by migrations of seastars in aggregative waves that eventually affect the entire reef system. The directional migration across reefs appears to be a search for prey as reef portions affected by dense seastar aggregations are rapidly depleted of living corals and subsequently left behind. Coral decline on impacted reefs occurs by the sequential consumption of species in the order of Acanthaster feeding preferences. Acanthaster outbreaks thus result in predictable alteration of the coral community structure. The outbreak we report here is among the most intense and devastating ever reported. Using a hierarchical, multi-scale approach, we also show how sessile benthic communities and resident coral-feeding fish assemblages were subsequently affected by the decline of corals. By elucidating the processes involved in an Acanthaster outbreak, our study contributes to comprehending this widespread disturbance and should thus benefit targeted management actions for coral reef ecosystems

MASCOT operations on Ryugu - focus on some specific tasks

Hayabusa2 is an asteroid sample return mission operated by the Japanese space agency, JAXA. It was launched in December 2014. In July 2018, the spacecraft has reached the mission target after a 4-year-long cruise. The objective is a C-type primordial asteroid called Ryugu, in search of organic and hydrated minerals that might give essential clues for the solar system formation. The small lander MASCOT (Mobile Asteroid surface SCOuT) carried aboard Hayabusa2 landed on the surface on the 3rd of October 2018 for reliminary in-situ investigations while the probe is aiming to study Ryugu on a global scale and to return samples to Earth. MASCOT was jointly developed by the German Aerospace Centre (DLR) and the Centre National d'Etudes Spatiales (CNES). It is equipped with a sensor suite consisting of four fully-fledged instruments. DLR was responsible for developing the MASCOT lander and ground segment, and was in charge of planning and conducting lander joint operations from MUSC. CNES supplied the hyperspectral IR spectrometer (MicrOmega, IAS Paris), antennae and power system, provided a support to operations and was in charge of the flight dynamics aspects of the mission. The 17 hours of on-asteroid operations exceeded expectations and the overall landing and operations were a huge success. Indeed, the characteristics of the Ryugu asteroid such as the shape and the gravity were known only after arrival of Hayabusa2 in July 2018 and the operating ccontext was very constrained but did not provide from fulfilling the objectives. This paper is a complement to the overall paper on MASCOT landing and first results. It will focus on several operational tasks such as communication and power subsystems assessments as well as flight dynamics computations needed in real time and for postprocessing

MASCOT - a Mobile Lander on-board Hayabusa2 Spacecraft - Operations on Ryugu

MASCOT (‘Mobile Asteroid Surface Scout’) is a 10 kg mobile surface science package part of JAXA’s Hayabusa2 sample return mission. The mission was launched in December 2014 from Tanegashima Space Center, Japan. The Hayabusa2 spacecraft reached the target asteroid in summer 2018. After a mapping phase of the asteroid and a landing site selection process the MASCOT lander was deployed to the surface on the 3rd of October 2018. MASCOT operated successfully for about 17 hours on the surface of Ryugu. It performed three relocation manoeuvres and one “Mini-Move” and returned 128 MBytes of data. MASCOT has been developed by the German Aerospace Center (DLR) in cooperation with the Centre National d’Etudes Spatiales (CNES). The main objectives were to perform in-situ investigations of the asteroid surface and to support the sampling site selection for the mother spacecraft. These objectives could be reached successfully. On 6th December 2020 (JST) Hayabusa returned successfully asteroid samples to the Earth

The MASCOT lander aboard Hayabusa2: The in-situ exploration of NEA (162173) Ryugu

After 3.5 years of cruise, and about 3 months in the vicinity of its target, the MASCOT lander was deployed successfully on October 3, 2018 by the Hayabusa2 spacecraft onto the C-type near-Earth asteroid (162173) Ryugu. After a free-fall of 5 ​min 51 ​s from an altitude of 41 ​m MASCOT experienced its first contact with the asteroid hitting a big boulder. The lander bounced for ~11 ​min 3 ​s before it came to rest. MASCOT was able to perform science measurements with its payload suite at 3 different locations on the surface of Ryugu. It investigated the fine-scale structure, multispectral reflectance, thermal characteristics and magnetic properties. The surface consists of very rugged terrain littered with large surface boulders. The in-situ measurements confirmed the absence of fine particles and dust as already implied by the remote sensing instruments aboard the Hayabusa2 spacecraft. After about 17 ​h of operations, the MASCOT mission terminated with the last communication contact as its primary batteries depleted. This paper summarizes the MASCOT mission covering its four years of in-flight operations, its preparation for the descent, landing and in-situ investigation on the asteroid Ryugu until the end of its operation