Project related news and papers

Project related news and papers (83)

 Interview coordinators

Dr. Santos Merino and Dr. Iban Quintana are the head of the Micro and Nanofabrication Unit and Ultra-Precision Processes Unit respectively. Their research at IK4-TEKNIKER is based on diagnostic and regenerative medicine in health, and on developing high added value products based on advanced manufacturing technologies. In this interview they talk about their experience as coordinators, the origin of the idea, objectives and actual stage of Neurimp project.

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Abstract

  • Reconstruction of functional peripheral nervous tissue is a challenging task. Complete recovery of lost sensory and motor functions can be rarely achieved due to the complex biochemical composition of the human body.
    Many approaches have been developed and applied with a different degree of success. The aim of this review is focused on the revision of today’s medical approaches to peripheral nervous tissue regeneration. Special attention is put on the most recent approaches that use solutions mimicking those elaborated by nature. The paper describes the anatomy of peripheral nerve tissue and deals with current understanding of biochemical processes involved in its development as well as in the body’s response to its damage. Next, the paper addresses new methods of nerve tissue reconstruction reflecting the anatomical and physiological basis of anatomical and physiological properties of peripheral nerves. In the final conclusions, recent breakthroughs in peripheral nerve regeneration are taken into accout to create an ideal approach to this field of tissue engineering.

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Abstract.

Electrospinning is a technique that can produce fibres in the nanoscale range. This process is useful for many applications, including fabrication of fibrous scaffolds for fibrocartilage tissue engineering. For this application, cell attachment and tissue development is influenced by fibre morphology and mechanical properties. This electrospinning study investigated the influence of rotating collector design on morphology and mechanical properties of electrospun polycaprolactone fibre. The experiment employed 4 mandrel designs: 1) full surface of aluminium; 2) with gap feature; 3) with gap feature and teflon support; 4) with gap feature and tape support. The highest elastic modulus was obtained from mandrel with gap and tape support, which was 24.6 MPa and significantly higher compared to fibres acquired from other collector designs. Fibre diameter attained was identical across the different collectors, ranging from 0.5 - 2 μm. Gap introduction showed enhanced alignment in the resultant fibre. It can be concluded that fibre alignment and tensile properties can be improved by simply modifying the collector design. This improved fibre mat can be developed as a biomaterial for fibrocartilage tissue engineering scaffolds.

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Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-l-lactide acid fibers in their lumen were fabricated. Rat Schwann cells were seeded within the conduits and cultured for 10 days. The conduits possessed a three-layered porous structure that impeded the leakage of the cells seeded in their interior and made them impervious to cell invasion from the exterior, while allowing free transport of nutrients and other molecules needed for cell survival. The channel’s surface acted as a template for the formation of a cylindrical sheath-like tapestry of Schwann cells continuously spanning the whole length of the lumen. Schwann-cell tubes having a diameter of around 0.5 mm and variable lengths can thus be generated. This structure is not found in nature and represents a truly engineered tissue, the outcome of the specific cell–material interactions. The conduits might be useful to sustain and protect cells for transplantation, and the biohybrids here described, together with neuronal precursors, might be of help in building bridges across significant distances in the central and peripheral nervous system.

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Three-dimensional (3D) bioprinting comprises a group of biofabrication technologies for the additive manufacturing of 3D constructs by precisely printing biocompatible materials, cells and biochemicals in predesigned spatial positions. These technologies have been successfully applied to fabricate biodegradable 3D constructs with intricate architectures and heterogeneous composition, assuming a pivotal role in the field of tissue engineering. However, the full implementation of bioprinting strongly depends on the development of novel biomaterials exhibiting fast crosslinking schemes and appropriate printability, cell-compatibility and biomechanical properties. Photocrosslinkable hydrogels are attractive materials for bioprinting as they provide fast polymerization under cell-compatible conditions and exceptional spatiotemporal control over the gelation process. Photopolymerization can also be performed during the bioprinting to promote the instantaneous formation of hydrogel with high well-defined architecture and structural stability. In this review paper, we summarize the most recent developments on bioprinting of photocrosslinkable biodegradable hydrogels for tissue engineering, focusing on the chemical modification strategies and the combination of photocrosslinking reactions with other gelation modalities. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42458.

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Background: Direct neurorrhaphy, nerve grafting interposition and neurotization are the options for nerve repair in children, whereas few reports about using nerve conduits (tubulization) are referred to pediatrics in the literature. The authors present their experience about nerve repairing by means of nerve tubes during the developmental age when the harvesting of nerve grafts and also vein grafts of adequate caliber for bridging nerve defects is difficult. A critical review of their case series offers indications for using nerve conduits in pediatrics.
Materials and Methods: Fifteen patients were treated using the nerve tubulization; nine patients were affected by obstetrical brachial plexus palsy (OBPP) while six were suffering from peripheral nerve injuries (PNIs).
Results: In patients suffering from OBPP, we observed 1 good, 3 fair and 5 bad results. In the PNI group, we observed 4 patients who had good results while only 2 had a bad outcome. No fair results were observed.
Conclusions: In peripheral nerve repairing in children by using nerve conduits, the outcome has been widely effective even when dealing with mixed and motor nerve, thus nerve tubulization might be considered as an alternative to nerve grafting. Conversely, considering the uncertain result obtained in brachial plexus repairing, the conduits cannot be considered as afirst choice of treatment in brachial plexus reconstruction.

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Abstract

Background: Nerve repair using photochemically bonded human amnion nerve wraps can result in superior outcomes in comparison with standard suture. When applied to nerve grafts, efficacy has been limited by proteolytic degradation of bonded amnion during extended periods of recovery. Chemical cross-linking of amnion before bonding may improve wrap durability and efficacy.

Methods: Three nerve wraps (amnion, cross-linked amnion, and cross-linked swine intestinal submucosa) and three fixation methods (suture, fibrin glue, and photochemical bonding) were investigated. One hundred ten Lewis rats had 15-mm left sciatic nerve gaps repaired with isografts. Nine groups (n = 10) had isografts secured by one of the aforementioned wrap/fixation combinations. Positive and negative control groups (n = 10) were repaired with graft and suture and no repair, respectively. Outcomes were assessed using sciatic function index, muscle mass retention, and histomorphometry. Statistical analysis was performed using analysis of variance and the post hoc Bonferroni test (p < 0.05).

Results: Cross-linking improved amnion durability. Photochemically bonded cross-linked amnion recovered the greatest sciatic function index, although this was not significant in comparison with graft and suture. Photochemically bonded cross-linked amnion recovered significantly greater muscle mass (67.3 ± 4.4 percent versus 60.0 ± 5.2 percent; p = 0.02), fiber diameter, axon diameter, and myelin thickness (6.87 ± 2.23 μm versus 5.47 ± 1.70 μm; 4.51 ± 1.83 μm versus 3.50 ± 1.44 μm; and 2.35 ± 0.64 μm versus 1.96 ± 0.47 μm, respectively) in comparison with graft and suture.

Conclusion: Light-activated sealing of cross-linked human amnion results in superior outcomes when compared with conventional suture.

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Abstract

A 3D printing methodology for the design, optimization, and fabrication of a custom nerve repair technology for the regeneration of complex peripheral nerve injuries containing bifurcating sensory and motor nerve pathways is introduced. The custom scaffolds are deterministically fabricated via a microextrusion printing principle using 3D models, which are reverse engineered from patient anatomies by 3D scanning. The bifurcating pathways are augmented with 3D printed biomimetic physical cues (microgrooves) and path-specific biochemical cues (spatially controlled multicomponent gradients). In vitro studies reveal that 3D printed physical and biochemical cues provide axonal guidance and chemotractant/chemokinetic functionality. In vivo studies examining the regeneration of bifurcated injuries across a 10 mm complex nerve gap in rats showed that the 3D printed scaffolds achieved successful regeneration of complex nerve injuries, resulting in enhanced functional return of the regenerated nerve. This approach suggests the potential of 3D printing toward advancing tissue regeneration in terms of: (1) the customization of scaffold geometries to match inherent tissue anatomies; (2) the integration of biomanufacturing approaches with computational modeling for design, analysis, and optimization; and (3) the enhancement of device properties with spatially controlled physical and biochemical functionalities, all enabled by the same 3D printing process.

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Abstract

  • Polymeric biomaterials are often used for stimulating nerve regeneration. Among different conduits, poly(lactide acid) – PLA polymer is considered to be a good substrate due to its biocompatibility and resorbable characteristics. This polymer is an aliphatic polyester which has been mostly used in biomedical application. It is an organic compound with low allergenic potential, low toxicity, high biocompatibility and predictable kinetics of degradation. In this study we fabricated and evaluated a PLA microporous hollow fiber as a conduit for its ability to bridge a nerve gap in a mouse sciatic nerve injury model. The PLA conduit was prepared from a polymer solution, throughout extrusion technique. The left sciatic nerve of C57BL/6 mouse was transected and the nerve stumps were placed into a resorbable PLA (PLA group) or a PCL conduit (PCL group), n = 5 each group. We have also used another group in which the nerves were repaired by autograft (autograft group, n = 5). Motor function was analyzed according to sciatic functional index (SFI). After 56 days, the regenerated nerves were processed for light and electron microscopy and morphometric analyses were performed. A quantitative analysis of regenerated nerves showed significant increase in the number of myelinated fibers and blood vessels in animals that received PLA conduit. The PLA group exhibited better overall tissue organization compared to other groups. Presenting well-organized bundles, many regenerating clusters composed of preserved nerve fibers surrounded by layers of compacted perineurium-like cells. Also the SFI revealed a significant improvement in functional recovery. This work suggests that PLA conduits are suitable substrate for cell survival and it provides an effective strategy to be used to support axonal growth becoming a potential alternative to autograft.

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  • The European Society for the Study of Peripheral Nerve Repair and Regeneration (ESPNR) has been founded in Bruxelles on May 27th 2014
  • on occasion of the International Workshop on Intrinsic and Extrinsic Mechanisms of Axonal Regeneration organized by the EU-funded BIOHYBRID Consortium.
  • ESPNR aims bring together basic and clinical scientists with the goal of promoting the study on peripheral nerve repair and regeneration both in the pre-clinical and clinical level.
  • ESPNR also organizes the International Symposium on Peripheral Nerve Repair and Regeneration (ISPNR) as well as other scientific events on related topics.

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