Engineered neural tissue made using hydrogels derived from decellularised tissues for the regeneration of peripheral nerves.

Engineered neural tissue (EngNT) promotes in vivo axonal regeneration. Decellularised materials (dECM) are complex biologic scaffolds that can improve the cellular environment and also encourage positive tissue remodelling in vivo. We hypothesised that we could incorporate a hydrogel derived from a decellularised tissue (dECMh) into EngNT, thereby providing an alternative to the currently used purified collagen I hydrogel for the first time. Decellularisation was carried out on bone (B-ECM), liver (LIV-ECM), and small intestinal (SIS-ECM) tissues and the resultant dECM was biochemically and mechanically characterised. dECMh differed in mechanical and biochemical properties that likely had an effect on Schwann cell behaviour observed in metabolic activity and contraction profiles. Cellular alignment was observed in tethered moulds within the B-ECM and SIS-ECM derived hydrogels only. No difference was observed in dorsal root ganglia (DRG) neurite extension between the dECMh groups and collagen I groups when applied as a coverslip coating, however, when DRG were seeded atop EngNT constructs, only the B-ECM derived EngNT performed similarly to collagen I derived EngNT. B-ECM EngNT further exhibited similar axonal regeneration to collagen I EngNT in a 10 mm gap rat sciatic nerve injury model after 4 weeks. Our results have shown that various dECMh can be utilised to produce EngNT that can promote neurite extension in vitro and axonal regeneration in vivo. STATEMENT OF SIGNIFICANCE: Nerve autografts are undesirable due to the sacrifice of a patient's own nerve tissue to repair injuries. Engineered neural tissue (EngNT) is a type of living artificial tissue that has been developed to overcome this. To date, only a collagen hydrogel has been shown to be effective in the production and utilisation of EngNT in animal models. Hydrogels may be made from decellularised extracellular matrix derived from many tissues. In this study we showed that hydrogels from various tissues may be used to create EngNT and one was shown to comparable to the currently used collagen based EngNT in a rat sciatic nerve injry model.

Printing biohybrid materials for bioelectronic cardio-3D-cellular constructs.

Conductive hydrogels are emerging as promising materials for bioelectronic applications as they minimize the mismatch between biological and electronic systems. We propose a strategy to bioprint biohybrid conductive bioinks based on decellularized extracellular matrix (dECM) and multiwalled carbon nanotubes. These inks contained conductive features and morphology of the dECM fibers. Electrical stimulation (ES) was applied to bioprinted structures containing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). It was observed that in the absence of external ES, the conductive properties of the materials can improve the contractile behavior of the hPSC-CMs, and this effect is enhanced under the application of external ES. Genetic markers indicated a trend toward a more mature state of the cells with upregulated calcium handling proteins and downregulation of calcium channels involved in the generation of pacemaking currents. These results demonstrate the potential of our strategy to manufacture conductive hydrogels in complex geometries for actuating purposes.

30-year record of Himalaya mass-wasting reveals landscape perturbations by extreme events.

In mountainous environments, quantifying the drivers of mass-wasting is fundamental for understanding landscape evolution and improving hazard management. Here, we quantify the magnitudes of mass-wasting caused by the Asia Summer Monsoon, extreme rainfall, and earthquakes in the Nepal Himalaya. Using a newly compiled 30-year mass-wasting inventory, we establish empirical relationships between monsoon-triggered mass-wasting and monsoon precipitation, before quantifying how other mass-wasting drivers perturb this relationship. We find that perturbations up to 5 times greater than that expected from the monsoon alone are caused by rainfall events with 5-to-30-year return periods and short-term (< 2 year) earthquake-induced landscape preconditioning. In 2015, the landscape preconditioning is strongly controlled by the topographic signature of the Gorkha earthquake, whereby high Peak Ground Accelerations coincident with high excess topography (rock volume above a landscape threshold angle) amplifies landscape damage. Furthermore, earlier earthquakes in 1934, 1988 and 2011 are not found to influence 2015 mass-wasting.