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Mainz, Germany

Meyer C.,Hannover Medical School | Meyer C.,Center for Systems Neuroscience Hanover | Wrobel S.,Hannover Medical School | Wrobel S.,Center for Systems Neuroscience Hanover | And 10 more authors.
Cell Transplantation

Critical length nerve defects in the rat sciatic nerve model were reconstructed with chitosan nerve guides filled with Schwann cells (SCs) containing hydrogel. The transplanted SCs were naive or had been genetically modified to overexpress neurotrophic factors, thus providing a cellular neurotrophic factor delivery system. Prior to the assessment in vivo, in vitro studies evaluating the properties of engineered SCs overexpressing glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF-218kDa) demonstrated their neurite outgrowth inductive bioactivity for sympathetic PC-12 cells as well as for dissociated dorsal root ganglion cell drop cultures. SCs within NVR-hydrogel, which is mainly composed of hyaluronic acid and laminin, were delivered into the lumen of chitosan hollow conduits with a 5% degree of acetylation. The viability and neurotrophic factor production by engineered SCs within NVR-Gel inside the chitosan nerve guides was further demonstrated in vitro. In vivo we studied the outcome of peripheral nerve regeneration after reconstruction of 15-mm nerve gaps with either chitosan/NVR-Gel/SCs composite nerve guides or autologous nerve grafts (ANGs). While ANGs did guarantee for functional sensory and motor regeneration in 100% of the animals, delivery of NVR-Gel into the chitosan nerve guides obviously impaired sufficient axonal outgrowth. This obstacle was overcome to a remarkable extent when the NVR-Gel was enriched with FGF-218kDa overexpressing SCs. © 2016 Cognizant, LLC. Source

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-2 | Award Amount: 7.76M | Year: 2011

The BIOHYBRID consortium was build up with the overall aim to develop, in a preclinical perspective, an innovative biohybrid artificial nerve device for the regenerative treatment of traumatic injuries of peripheral nerves. This consortium consists of three active and well integrated SMEs as well as seven academic partners that are recognised leaders in the scientific areas of interest for this project. Furthermore, another partner has substantiated expertises to meet the regulatory work for ATMP development. Traumatic injuries of peripheral nerves represent a major cause for morbidity and morbility in Europe and their social impact is considerably high. It has been estimated that the incidence of peripheral nerve injuries derived from trauma is about 300,000 cases per year. Moreover, nerve injuries are an important component of traumatic limb amputations, with an incidence of 2/100,000 persons per year described for hand amputations. Therefore, repair and regeneration of peripheral nerve injuries represent a major field where clinical application of innovative therapies in regenerative medicine should be sought. Peripheral nerve fibers are able to regenerate and lead to functional recovery provided that an appropriate milieu and guide is available. However, the clinical outcome of neural repair after extended substance loss after nerve injury is often unsatisfactory and therefore innovative strategies for improving the outcome after neural damage are in demand. The main objective of the BIOHYBRID project is the development of a regenerative therapy using an innovative biohybrid artificial nerve device with the goal of repairing damaged nerve trunks. The work program includes an integrated experimental approach bringing together the main aspects of regenerative medicine: a) reconstructive microsurgery, b) regenerative scaffolds and c) transplantation. This approach will allow the biological pre-fabrication of biohybrid nerve devices, their transplantation into nerve gaps in various animal models and the comprehensive evaluation of the regenerative outcome. The SME involvement, for the first time in this biomedical field, will not be limited to production and supply of materials and services but includes also active participation in the conduction of the experiments for in vivo preclinical assessment and follow-up. Based on the extensive basic and clinical experience within this consortium a biohybrid artificial nerve device will be developed together with standardised application and evaluation parameters. A key objective of this study will be to generate, for the first time, a protocol that can serve as a template for future clinical trials in the regenerative therapy of damaged peripheral nerves. The BIOHYBRID project with its consortium partners combines excellent expertise to successfully reach the objectives and stands therfore on the front line of regenerative medicine approaches.

Medovent GmbH | Date: 2010-02-02

A fluid-swellable fiber in particular for the use as a surgical suture, the fiber comprising chitosan, the fibers swelling ratio being less than 100%, and a fabric comprising the fiber. Moreover, a method of manufacturing from a chitosan-containing solution a fiber comprising chitosan, wherein during manufacture, the solution is brought into contact with a coagulation medium containing at least one organic solvent, a method of removing a fiber from a living organism, wherein the fiber is at least partly dissolved in a solvent applied from the outside, and a kit comprising a chitosan containing fiber and a solvent for at least partly dissolving the fiber.

Gonzalez-Perez F.,Autonomous University of Barcelona | Cobianchi S.,Autonomous University of Barcelona | Geuna S.,University of Turin | Barwig C.,Medovent GmbH | And 3 more authors.

Biosynthetic guides can be an alternative to nerve grafts for reconstructing severely injured peripheral nerves. The aim of this study was to evaluate the regenerative capability of chitosan tubes to bridge critical nerve gaps (15 mm long) in the rat sciatic nerve compared with silicone (SIL) tubes and nerve autografts (AGs). A total of 28 Wistar Hannover rats were randomly distributed into four groups (n = 7 each), in which the nerve was repaired by SIL tube, chitosan guides of low (∼2%, DAI) and medium (∼5%, DAII) degree of acetylation, and AG. Electrophysiological and algesimetry tests were performed serially along 4 months follow-up, and histomorphometric analysis was performed at the end of the study. Both groups with chitosan tubes showed similar degree of functional recovery, and similar number of myelinated nerve fibers at mid tube after 4 months of implantation. The results with chitosan tubes were significantly better compared to SIL tubes (P < 0.01), but lower than with AG (P < 0.01). In contrast to AG, in which all the rats had effective regeneration and target reinnervation, chitosan tubes from DAI and DAII achieved 43 and 57% success, respectively, whereas regeneration failed in all the animals repaired with SIL tubes. This study suggests that chitosan guides are promising conduits to construct artificial nerve grafts. © 2014 Wiley Periodicals, Inc. Microsurgery 35:300-308, 2015. © 2014 Wiley Periodicals, Inc. Source

Gnavi S.,University of Turin | Barwig C.,Medovent GmbH | Freier T.,Medovent GmbH | Haastert-Talini K.,Hannover Medical School | And 2 more authors.
International Review of Neurobiology

Various biomaterials have been proposed to build up scaffolds for promoting neural repair. Among them, chitosan, a derivative of chitin, has been raising more and more interest among basic and clinical scientists. A number of studies with neuronal and glial cell cultures have shown that this biomaterial has biomimetic properties, which make it a good candidate for developing innovative devices for neural repair. Yet, in vivo experimental studies have shown that chitosan can be successfully used to create scaffolds that promote regeneration both in the central and in the peripheral nervous system. In this review, the relevant literature on the use of chitosan in the nervous tissue, either alone or in combination with other components, is overviewed. Altogether, the promising in vitro and in vivo experimental results make it possible to foresee that time for clinical trials with chitosan-based nerve regeneration-promoting devices is approaching quickly. © 2013 Elsevier Inc. Source

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