Tissue Engineering Scaffold Slowly Releasing Neurotrophic Factors to Bridge Long Peripheral Nerve Defect

Consistent application of neurotropic factors is necessary in peripheral nerve regeneration, yet challenging to achieve. Here we used a novel neurotropic factor controlled release system consisted of fibrin, fibronectin and hydrogel to slowly release two neurotrophic factors. At the same time, physiological saline and reverse nerve suturing were used as negative and positive control. A year after surgery, animals which were treated by neurotrophic factor slow release system achieved far better neural regeneration and myelination, as well as superior recovery of hindfoot than the negative control group. In the meanwhile, the results in the experimental group are still inferior to the nerve allograft group. In can be concluded from those results that, consistent releasing of neurotrophic factors can significantly promote long peripheral nerve regeneration, but still short of achieving the results same as the gold standard of autologous nerve grafting.

Comparison of Collagen and Human Amniotic Membrane Nerve Wraps and Conduits for Peripheral Nerve Repair in Preclinical Models: A Systematic Review of the Literature

Introduction Collagen and human amniotic membrane (hAM) are Food and Drug Administration (FDA)-approved biomaterials that can be used as nerve wraps or conduits for repair of peripheral nerve injuries. Both biomaterials have been shown to reduce scarring and fibrosis of injured peripheral nerves. However, comparative advantages and disadvantages have not been definitively shown in the literature. The purpose of this systematic review is to comprehensively evaluate the literature regarding the roles of hAM and collagen nerve wraps and conduits on peripheral nerve regeneration in preclinical models. Methods The MEDLINE database was queried using the PubMed search engine on July 7, 2019, with the following search strategy: (“amniotic membrane” OR “amnion”) OR (“collagen conduit” OR “nerve wrap”)] AND “nerve.” All resulting articles were screened by two independent reviewers. Nerve type, lesion type/injury model, repair type, treatment, and outcomes were assessed. Results Two hundred and fifty-eight articles were identified, and 44 studies remained after application of inclusion and exclusion criteria. Seventeen studies utilized hAM, whereas 27 studies utilized collagen wraps or conduits. Twenty-three (85%) of the collagen studies utilized conduits, and four (15%) utilized wraps. Six (35%) of the hAM studies utilized conduits and 11 (65%) utilized wraps. Two (9%) collagen studies involving a conduit and one (25%) involving a wrap demonstrated at least one significant improvement in outcomes compared with a control. While none of the hAM conduit studies showed significant improvements, eight (73%) of the studies investigating hAM wraps showed at least one significant improvement in outcomes. Conclusion The majority of studies reported positive outcomes, indicating that collagen and hAM nerve wraps and conduits both have the potential to enhance peripheral nerve regeneration. However, relatively few studies reported significant findings, except for studies evaluating hAM wraps. Preclinical models may help guide clinical practice regarding applications of these biomaterials in peripheral nerve repair.

Application of Hybrid Electrically Conductive Hydrogels Promotes Peripheral Nerve Regeneration

Peripheral nerve injury (PNI) occurs frequently, and the prognosis is unsatisfactory. As the gold standard of treatment, autologous nerve grafting has several disadvantages, such as lack of donors and complications. The use of functional biomaterials to simulate the natural microenvironment of the nervous system and the combination of different biomaterials are considered to be encouraging alternative methods for effective tissue regeneration and functional restoration of injured nerves. Considering the inherent presence of an electric field in the nervous system, electrically conductive biomaterials have been used to promote nerve regeneration. Due to their singular physical properties, hydrogels can provide a three-dimensional hydrated network that can be integrated into diverse sizes and shapes and stimulate the natural functions of nerve tissue. Therefore, conductive hydrogels have become the most effective biological material to simulate human nervous tissue’s biological and electrical characteristics. The principal merits of conductive hydrogels include their physical properties and their electrical peculiarities sufficient to effectively transmit electrical signals to cells. This review summarizes the recent applications of conductive hydrogels to enhance peripheral nerve regeneration.

Therapeutic Low-Intensity Ultrasound for Peripheral Nerve Regeneration – A Schwann Cell Perspective

Peripheral nerve injuries are common conditions that can arise from trauma (e.g., compression, severance) and can lead to neuropathic pain as well as motor and sensory deficits. Although much knowledge exists on the mechanisms of injury and nerve regeneration, treatments that ensure functional recovery following peripheral nerve injury are limited. Schwann cells, the supporting glial cells in peripheral nerves, orchestrate the response to nerve injury, by converting to a “repair” phenotype. However, nerve regeneration is often suboptimal in humans as the repair Schwann cells do not sustain their repair phenotype long enough to support the prolonged regeneration times required for successful nerve regrowth. Thus, numerous strategies are currently focused on promoting and extending the Schwann cells repair phenotype. Low-intensity ultrasound (LIU) is a non-destructive therapeutic approach which has been shown to facilitate peripheral nerve regeneration following nerve injury in rodents. Still, clinical trials in humans are scarce and limited to small population sizes. The benefit of LIU on nerve regeneration could possibly be mediated through the repair Schwann cells. In this review, we discuss the known and possible molecular mechanisms activated in response to LIU in repair Schwann cells to draw support and attention to LIU as a compelling regenerative treatment for peripheral nerve injury.

Contralateral C7 nerve transfer in the treatment of upper-extremity paralysis: a review of anatomical basis, surgical approaches, and neurobiological mechanisms

The previous three decades have witnessed a prosperity of contralateral C7 nerve (CC7) transfer in the treatment of upper-extremity paralysis induced by both brachial plexus avulsion injury and central hemiplegia. From the initial subcutaneous route to the pre-spinal route and the newly-established post-spinal route, this surgical operation underwent a series of innovations and refinements, with the aim of shortening the regeneration distance and even achieving direct neurorrhaphy. Apart from surgical efforts for better peripheral nerve regeneration, brain involvement in functional improvements after CC7 transfer also stimulated scientific interest. This review summarizes recent advances of CC7 transfer in the treatment of upper-extremity paralysis of both peripheral and central causes, which covers the neuroanatomical basis, the evolution of surgical approach, and central mechanisms. In addition, motor cortex stimulation is discussed as a viable rehabilitation treatment in boosting functional recovery after CC7 transfer. This knowledge will be beneficial towards improving clinical effects of CC7 transfer.

Influence of electrical stimulation on peripheral nerve regeneration: Protocol for a systematic review

This is a protocol for a systematic review (intervention). Electrical stimulation (ES) is a therapeutic strategy used to improve peripheral nerve regeneration that involves the application of electrical fields of constant or varying frequency. We are going to lead a literature search to identify all published and unpublished randomized controlled trials that describe the use of ES in patients with peripheral nerve injury. We will compare: Electrical stimulation (application of electrical fields of constant or varying frequency) versus sham in patients with peripheral nerve injury; Electrical stimulation versus standard treatment (physiotherapy) in patients with peripheral nerve injury; Electrical stimulation versus no treatment in patients with peripheral nerve injury. Considering the scenario of very numerous strategies and different techniques of ES to stimulate nerve regeneration, decisions to recommend them should consider these uncertainties and should be summarized intended its application in clinical practice. The objective of this review is to assess the influence of electrical stimulation (ES) on nerve regeneration in individuals with peripheral nerve injury.