Peripheral Nerve Tissue Engineering And Regeneration

This updatable book provides an accessible informative overview of the current state of the art in nerve repair research.The introduction includes history of nerve repair research and establishes key concepts and terminology and will be followed by sections that represent the main areas of interest in the field: (1) Biomaterials, (2) Therapeutic Cells, (3) Drug, Gene and Extracellular Vesicle Therapies, (4) Research Models and (5) Clinical Translation. Each section will contain 3 - 6 chapters, capturing the full breadth of relevant technology. Bringing together diverse disciplines under one overarching theme echoes the multidisciplinary approach that underpins modern tissue engineering and regenerative medicine. Each chapter will be written in an accessible manner that will facilitate interest and understanding, providing a comprehensive single reference source. The updatable nature of the work will ensure that it can evolve to accommodate future changes and new technologies. The main readership for this work will be researchers and clinicians based in academic, industrial and healthcare settings all over the world.

This issue of International Review of Neurobiology brings together cutting-edge research on tissue engineering of the peripheral nerve. It reviews current knowledge and understanding, provides a starting point for researchers and practitioners entering the field, and builds a platform for further research and discovery. This volume of International Review of Neurobiology brings together cutting-edge research on tissue engineering of the peripheral nerve It reviews current knowledge and understanding, provides a starting point for researchers and practitioners entering the field, and builds a platform for further research and discovery

This issue of International Review of Neurobiology brings together cutting-edge research on tissue engineering of the peripheral nerve. It reviews current knowledge and understanding, provides a starting point for researchers and practitioners entering the field, and builds a platform for further research and discovery. This volume covers the cutting-edge research on tissue engineering of the peripheral nerve

Peripheral nerve injuries are a high-incidence clinical problem that greatly affects patients' quality of life. Despite continuous refinement of microsurgery techniques, peripheral nerve repair still stands as one of the most challenging tasks in neurosurgery, as functional neuromuscular recovery is rarely satisfactory in these patients. Therefore, the improvement of surgical techniques and the clinical application of innovative therapies have been intensively studied worldwide. Direct nerve repair with epineural end-to-end sutures is still the gold standard treatment for severe neurotmesis injuries but only in cases where well-vascularized tension-free coaptation can be achieved. When peripheral nerve injury originates a significant gap between the nerve stumps, nerve grafts are required, with several associated disadvantages. Therefore, the development of scaffolds by tissue engineering can provide efficient treatment alternatives to stimulate optimum clinical outcome. Nerve conduit tailoring involves reaching ideal wall pores, using electrospinning techniques in their fabrication, surface coating with extracellular matrix materials, and adding of growth factors or cell-based therapies, among other possibilities. Also, intraluminal cues are employed such as the filling with hydrogels, inner surface modification, topographical design, and the introduction of neurotrophic factors, antibiotics, anti-inflammatories and other pharmacological agents. A comprehensive state of the art of surgical techniques, tissue-engineered nerve graft scaffolds, and their application in nerve regeneration, the advances in peripheral nerve repair and future perspectives will be discussed, including surgeons' and researchers' own large experience in this field of knowledge.

Combating neural degeneration from injury or disease is extremely difficult in the brain and spinal cord, i.e. central nervous system (CNS). Unlike the peripheral nerves, CNS neurons are bombarded by physical and chemical restrictions that prevent proper healing and restoration of function. The CNS is vital to bodily function, and loss of any part of it can severely and permanently alter a person's quality of life. Tissue engineering could offer much needed solutions to regenerate or replace damaged CNS tissue. This review will discuss current CNS tissue engineering approaches integrating scaffolds, cells and stimulation techniques. Hydrogels are commonly used CNS tissue engineering scaffolds to stimulate and enhance regeneration, but fiber meshes and other porous structures show specific utility depending on application. CNS relevant cell sources have focused on implantation of exogenous cells or stimulation of endogenous populations. Somatic cells of the CNS are rarely utilized for tissue engineering; however, glial cells of the peripheral nervous system (PNS) may be used to myelinate and protect spinal cord damage. Pluripotent and multipotent stem cells offer alternative cell sources due to continuing advancements in identification and differentiation of these cells. Finally, physical, chemical, and electrical guidance cues are extremely important to neural cells, serving important roles in development and adulthood. These guidance cues are being integrated into tissue engineering approaches. Of particular interest is the inclusion of cues to guide stem cells to differentiate into CNS cell types, as well to guide neuron targeting. This review should provide the reader with a broad understanding of CNS tissue engineering challenges and tactics, with the goal of fostering the future development of biologically inspired designs. Table of Contents: Introduction / Anatomy of the CNS and Progression of Neurological Damage / Biomaterials for Scaffold Preparation / Cell Sources for CNS TE / Stimulation and Guidance / Concluding Remarks

Interest in the study of peripheral nerve repair and regeneration has increased significantly over the last twenty years and today the number of nerve reconstructions performed is progressively increasing due to the continuous improvement in surgical technology and to the spread of microsurgical skills among surgeons worldwide. This volume of International Review of Neurobiology providdes an overview of the state of the art knowledge in peripheral nerve repair and regeneration by bringing together a number of reviews that critically address some the most important issues in this biomedical field.

There has been an increased interest in the development of nerve repair devices to improve peripheral nerve regeneration following injury. The aim of this study was to investigate whether nerve repair devices containing genetically modified cells overexpressing VEGF-A165 would augment regeneration. An in vitro proof-of-concept study was carried out to deliver marker genes (luciferase and eGFP) to a rat Schwann cell line (SCL4.1/F7) using a lentiviral vector. The transduced cells were used to produce engineered neural tissue and bioluminescence imaging was used to assess cell viability in the constructs. It was initially thought the presence of the luciferase gene in the expression cassette would allow real-time and sustained imaging of the cells in the engineered neural tissue. However, while bioluminescence imaging provided an indication of cell viability in vitro, it proved to be ineffective for in vivo and ex vivo imaging. Having established that SCL4.1/F7 cells were amenable to lentiviral transduction, a lentiviral vector delivering the VEGF-A165 gene was designed and produced. The VEGF-A165 produced by the transduced SCL4.1/F7 cells increased endothelial cell viability, migration and tube formation in vitro. It also increased SCL4.1/F7 cell proliferation and migration. SCL4.1/F7 cells overexpressing VEGF-A165 were found to increase endothelial cell network formation and neurite length in 3D co- culture models. Foetal human neural stem cells and rat adipose derived stem cells were also successfully transduced with the lentiviral vector delivering VEGF-A165. Based on the in vitro results, it was postulated that EngNT made from SCL4.1/F7 cells overexpressing VEGF-A165 implanted into a rat model of sciatic nerve injury would enhance regeneration. Unexpectedly, a pilot study revealed that this did not result in improved functional recovery or increased axon and blood vessel counts compared to controls. The results from this study highlight that attention needs to be paid to the dose and duration of expression of VEGF-A165 to optimise both its angiogenic and neurotrophic effects.