Engineered neural tissue made using clinical-grade human neural stem cells supports regeneration in a long gap peripheral nerve injury model

A surgical autograft remains the clinical gold-standard therapy for gap repair following peripheral nerve injury, however, challenges remain with achieving full recovery and reducing donor-site morbidity. Engineered neural tissue (EngNT) manufactured using differentiated CTX0E03 human stem cells (EngNT-CTX) has been developed as a potential ‘off the shelf’ allogeneic autograft replacement. Ensheathed within a collagen membrane developed to facilitate biomechanical integration, EngNT-CTX was used to bridge a critical-length (15 mm) sciatic nerve gap injury in athymic nude rats. The effectiveness of EngNT-CTX was compared to an autograft using outcome measures that assessed neuronal regeneration and functional recovery at 8 and 16 weeks. At both time points EngNT-CTX restored electrophysiological nerve conduction and functional reinnervation of downstream muscles to the same extent as the autograft. Histological analysis confirmed that more motor neurons had successfully regenerated through the repair in EngNT-CTX in comparison to the autograft at 8 weeks, which was consistent with the electrophysiology, with the number of motor neurons similar in both groups by 16 weeks. The total number of neurons (motor + sensory) was greater in autografts than EngNT-CTX at 8 weeks, indicating that more sensory fibres may have sprouted in those animals at this time point. In conclusion, this study provides evidence to support the effectiveness of EngNT-CTX as a replacement for the nerve autograft, as the functional regeneration assessed through histological and electrophysiological outcome measures demonstrated equivalent performance

An Optimized Collagen-Fibrin Blend Engineered Neural Tissue Promotes Peripheral Nerve Repair

Tissue engineering approaches in nerve regeneration often aim to improve results by bridging nerve defects with conduits that mimic key features of the nerve autograft. One such approach uses Schwann cell self-alignment and stabilization within collagen gels to generate engineered neural tissue (EngNT). In this study, we investigated whether a novel blend of fibrin and collagen could be used to form EngNT, as before EngNT design a beneficial effect of fibrin on Schwann cell proliferation was observed. A range of blend formulations was tested in terms of mechanical behavior (gel formation, stabilization, swelling, tensile strength, and stiffness), and lead formulations were assessed in vitro. A 90% collagen 10% fibrin blend was found to promote SCL4.1/F7 Schwann cell viability and supported the formation of aligned EngNT, which enhanced neurite outgrowth in vitro (NG108 cells) compared to formulations with higher and lower fibrin content. Initial in vivo tests in an 8 mm rat sciatic nerve model using rolled collagen-fibrin EngNT rods revealed a significantly enhanced axonal count in the midsection of the repair, as well as in the distal part of the nerve after 4 weeks. This optimized collagen-fibrin blend therefore provides a novel way to improve the capacity of EngNT to promote regeneration following peripheral nerve injury

The Effect of Hypothermic and Cryogenic Preservation on Engineered Neural Tissue

This study explored different approaches to preserve Engineered Neural Tissue (EngNT), a stabilised cellular collagen hydrogel containing columns of aligned Schwann cells for nervous system repair. The ability to preserve EngNT without disrupting cellular and extracellular components and structures is important for clinical translation and commercialisation. Stabilised cellular gels and EngNT constructs were preserved under various conditions and cell survival assessed using live/dead microscopy and metabolic assay. Optimal survival was recorded in hypothermic (4ºC) conditions for 2-3 days using Hibernate®-A media, and, for longer term cryogenic storage (liquid nitrogen), using a mixture of 60% Dulbecco's Modified Eagle's Medium media (DMEM), 30% foetal calf serum (FCS) and 10% dimethyl sulfoxide (DMSO). Functionality and structure of preserved EngNT was assessed in co-culture with dorsal root ganglion (DRG) neurons, which indicated that alignment of Schwann cells and the ability of EngNT to support and guide neuronal regeneration were not disrupted. The identification of conditions that preserve EngNT will inform development of storage and transport methodologies to support clinical and commercial translation of this technology and other therapies based on cellular hydrogels

Health and social outcomes of housing policies to alleviate fuel poverty

This chapter considers the implications of housing policies to alleviate fuel poverty, through a comprehensive narrative review of the literature on the consequences of living in fuel poverty and cold homes, and those on the health and social outcomes of home energy-efficiency improvements. The chapter shows that living in fuel poverty and cold homes has severe implications for people's physical health and their mental and social wellbeing, and that these can be alleviated with well-designed housing policies. It further shows that, while demand-led schemes are more likely than area-based ones to provide health benefits, any housing improvement program can have substantial positive social outcomes by improving living conditions and household finances. The policy implications of these findings are discussed