Kirsten Haastert-Talini
Hannover Medical School
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Featured researches published by Kirsten Haastert-Talini.
Biomaterials | 2013
Kirsten Haastert-Talini; Stefano Geuna; Lars B. Dahlin; Cora Meyer; Lena Stenberg; Thomas Freier; Claudia Heimann; Christina Barwig; L. Pinto; Stefania Raimondo; Giovanna Gambarotta; Silvina Ribeiro Samy; Nuno Sousa; António J. Salgado; Andreas Ratzka; Sandra Wrobel; Claudia Grothe
Biosynthetic nerve grafts are desired as alternative to autologous nerve grafts in peripheral nerve reconstruction. Artificial nerve conduits still have their limitations and are not widely accepted in the clinical setting. Here we report an analysis of fine-tuned chitosan tubes used to reconstruct 10 mm nerve defects in the adult rat. The chitosan tubes displayed low, medium and high degrees of acetylation (DAI: ≈ 2%, DA: ≈ 5%, DAIII: ≈ 20%) and therefore different degradability and microenvironments for the regenerating nerve tissue. Short and long term investigations were performed demonstrating that the chitosan tubes allowed functional and morphological nerve regeneration similar to autologous nerve grafts. Irrespective of the DA growth factor regulation demonstrated to be the same as in controls. Analyses of stereological parameters as well as the immunological tissue response at the implantation site and in the regenerated nerves, revealed that DAI and DAIII chitosan tubes displayed some limitations in the support of axonal regeneration and a high speed of degradation accompanied with low mechanical stability, respectively. The chitosan tubes combine several pre-requisites for a clinical acceptance and DAII chitosan tubes have to be judged as the most supportive for peripheral nerve regeneration.
Journal of Neurotrauma | 2011
Kirsten Haastert-Talini; Ruth Schmitte; Nele Korte; Dorothee Klode; Andreas Ratzka; Claudia Grothe
Short-term low-frequency electrical stimulation (ESTIM) of proximal peripheral nerve stumps prior to end-to-end coaptation or tubular bridging of small distances has been reported to increase preferential motor reinnervation and functional motor recovery in animal models and human patients undergoing carpal tunnel release surgery. We investigated the effects of ESTIM on regeneration across rat sciatic nerve gaps, which exceed distances that allow spontaneous regeneration. Three different reconstruction approaches were combined with ESTIM in the experimental groups. Nerve gaps (13 mm) were bridged using (I) nerve autotransplantation, (II) transplantation of differentially filled silicone tubes, or (III) transplantation of tubular grafts containing fibroblast growth factor-2 overexpressing Schwann cells (SCs) for gene therapy. The regeneration outcome was followed for up to 8 weeks, and functionally as well as histomorphometrically analyzed in comparison to non-stimulated control groups. Combining ESTIM with nerve autotransplantation significantly increased the nerve fiber density in the regenerated nerve, and the grade of functional recovery as detected by electrodiagnostic recordings from the gastrocnemius muscle. The combination of ESTIM with transplantation of naïve SCs increased the regeneration of gap-bridging nerve tissue. Although macroscopic tissue regeneration was not further improved after combining ESTIM with FGF-2(21/23-kD) gene therapy, the latter resulted in a high rate of regenerated nerves that functionally reconnected to the target muscle. Based on our results, brief ESTIM shows high potential to accelerate axonal as well as functional (motor and sensory) outcomes in the clinical setting of peripheral nerve gap reconstruction in human patients.
International Review of Neurobiology | 2013
Sara Gnavi; Christina Barwig; Thomas Freier; Kirsten Haastert-Talini; Claudia Grothe; Stefano Geuna
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.
Muscle & Nerve | 2011
Nele Korte; Henning C. Schenk; Claudia Grothe; Andrea Tipold; Kirsten Haastert-Talini
The advantage of minimally invasive electrodiagnostic methods for periodic evaluation of reinnervation at predefined time intervals does not seem to be widely recognized. In this study, using a rat model, we assessed the utility of periodic electrodiagnostic measurements for monitoring ongoing motor recovery after peripheral nerve injuries of differing severity.
BioMed Research International | 2014
Ofra Ziv-Polat; Abraham Shahar; Itay Levy; Hadas Skaat; Sara Neuman; Federica Fregnan; Stefano Geuna; Claudia Grothe; Kirsten Haastert-Talini; Shlomo Margel
Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (βNGF), glial cell-derived neurotrophic factor (GDNF), and basic fibroblast growth factor (FGF-2). Comparative stability studies of free versus conjugated factors revealed that the conjugated neurotrophic factors were significantly more stable in tissue cultures and in medium at 37°C. The biological effects of free versus conjugated neurotrophic factors were examined on organotypic dorsal root ganglion (DRG) cultures performed in NVR-Gel, composed mainly of hyaluronic acid and laminin. Results revealed that the conjugated neurotrophic factors enhanced early nerve fiber sprouting compared to the corresponding free factors. The most meaningful result was that conjugated-GDNF, accelerated the onset and progression of myelin significantly earlier than the free GDNF and the other free and conjugated factors. This is probably due to the beneficial and long-acting effect that the stabilized conjugated-GDNF had on neurons and Schwann cells. These conclusive results make NVR-Gel enriched with conjugated-GDNF, a desirable scaffold for the reconstruction of severed peripheral nerve.
Advanced Healthcare Materials | 2017
Stefan Wuttke; Andreas Zimpel; Thomas Bein; Simone Braig; Katharina Stoiber; Angelika M. Vollmar; Dominik Müller; Kirsten Haastert-Talini; Jörn Schaeske; Meike Stiesch; Gesa Zahn; Alexander Mohmeyer; Peter Behrens; Oliver Eickelberg; Deniz Ali Bölükbas; Silke Meiners
&NA; Metal‐organic frameworks (MOFs) are promising platforms for the synthesis of nanoparticles for diverse medical applications. Their fundamental design principles allow for significant control of the framework architecture and pore chemistry, enabling directed functionalization for nanomedical applications. However, before applying novel nanomaterials to patients, it is imperative to understand their potential health risks. In this study, the nanosafety of different MOF nanoparticles is analyzed comprehensively for diverse medical applications. The authors first evaluate the effects of MOFs on human endothelial and mouse lung cells, which constitute a first line of defense upon systemic blood‐mediated and local lung‐specific applications of nanoparticles. Second, we validated these MOFs for multifunctional surface coatings of dental implants using human gingiva fibroblasts. Moreover, biocompatibility of MOFs is assessed for surface coating of nerve guidance tubes using human Schwann cells and rat dorsal root ganglion cultures. The main finding of this study is that the nanosafety and principal suitability of our MOF nanoparticles as novel agents for drug delivery and implant coatings strongly varies with the effector cell type. We conclude that it is therefore necessary to carefully evaluate the nanosafety of MOF nanomaterials with respect to their particular medical application and their interacting primary cell types, respectively. &NA; Metal‐organic frameworks (MOFs) are a promising platform for the synthesis of porous nanoparticles for diverse medical applications. The aim of this study is to comprehensively investigate the nanosafety of different MOF nanoparticles for distinct fields of medical applications. Data presented here suggest the need to evaluate the nanosafety of each MOF nanomaterial with respect to their particular medical application. Figure. No caption available.
European Journal of Neuroscience | 2016
Giulia Ronchi; Kirsten Haastert-Talini; Benedetta Elena Fornasari; Isabelle Perroteau; Stefano Geuna; Giovanna Gambarotta
The peripheral nervous system has an intrinsic capability to regenerate, crucially related to the ability of Schwann cells (SC) to create a permissive environment, for example, through production of regeneration‐promoting neurotrophic factors. Survival, proliferation, migration and differentiation of SC into a myelinating phenotype during development and after injury is regulated by different Neuregulin1 (NRG1) isoforms. This study investigates the expression of different NRG1 isoforms and of their ErbB receptors in distal rat median nerve samples under regenerating conditions after a mild (crush) and more severe (end‐to‐end repair) injury and under degenerating condition. The expression of the NRG1/ErbB system was evaluated at mRNA and protein level, and demonstrated to be specific for distinct and consecutive phases following nerve injury and regeneration or the progress in degeneration. For the first time a detailed analysis of expression profiles not only of soluble and transmembrane NRG1 isoforms, but also of alpha and beta as well as type a, b and c isoforms is presented. The results of mRNA and protein expression pattern analyses were related to nerve ultrastructure changes evaluated by electron microscopy. In particular, transmembrane NRG1 isoforms are differentially regulated and proteolytically processed under regeneration and degeneration conditions. Soluble NRG1 isoforms alpha and beta, as well as type a and b, are strongly upregulated during axonal regrowth, while type c NRG1 isoform is downregulated. This is accompanied by an upregulation of ErbB receptors. This accurate regulation suggests that each molecule plays a specific role that could be clinically exploited to improve nerve regeneration.
European Journal of Neuroscience | 2016
Stefano Geuna; Stefania Raimondo; Federica Fregnan; Kirsten Haastert-Talini; Claudia Grothe
The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. However, the clinical outcome after nerve lesions is often far from satisfactory and the functional recovery is almost never complete. Therefore, a number of therapeutic approaches are being investigated, ranging from local delivery of trophic factors and other molecules to bioactive biomaterials and complex nerve prostheses. Translation of the new therapeutic approaches to the patient always requires a final pre‐clinical step using in vivo animal models. The need to limit as much as possible animal use in biomedical research, however, makes the preliminary use of in vitro models mandatory from an ethical point of view. In this article, the different types of in vitro models available today for the study of peripheral nerve regeneration have been ranked by adopting a three‐step stair model based on their increasing ethical impact: (i) cell line‐based models, which raise no ethical concern; (ii) primary cell‐based models, which have low ethical impact as animal use, although necessary, is limited; and (iii) organotypic ex vivo‐based models, which raise moderate ethical concerns as the use of laboratory animals is required although with much lower impact on animal wellbeing in comparison to in vivo models of peripheral nerve regeneration. This article aims to help researchers in selecting the best experimental approach for their scientific goals driven by the ‘Three Rs’ (3Rs) rules (Replacement, Reduction or Refinement of animal use in research) for scientific research.
BioMed Research International | 2014
Sven Duda; Lutz Dreyer; Peter Behrens; Soenke Wienecke; Tanmay Chakradeo; Birgit Glasmacher; Kirsten Haastert-Talini
We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerve transplantation (ANT). The mechanical biomaterial properties and the immunological impact of the grafts were assessed with histological techniques before and after transplantation in vivo. Furthermore during a 13-week examination period functional tests and electrophysiological recordings were performed and supplemented by nerve morphometry. The sheathing of the chitosan core with a polycaprolactone shell induced massive foreign body reaction and impairment of nerve regeneration. Although the isolated novel chitosan core did allow regeneration of axons in a similar size distribution as the ANT, the ANT was superior in terms of functional regeneration. We conclude that an outer polycaprolactone shell should not be used for the purpose of bioartificial nerve grafting, while 3D multichannel porous chitosan cores could be candidate scaffolds for structured nerve grafts.
International Journal of Nanomedicine | 2014
Michela Morano; Sandra Wrobel; Federica Fregnan; Ofra Ziv-Polat; Abraham Shahar; Andreas Ratzka; Claudia Grothe; Stefano Geuna; Kirsten Haastert-Talini
Purpose Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR) whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and transplantation. Methods Here, we comparatively investigated the bioactivity of selected neurotrophic factors conjugated to iron oxide nanoparticles (np-NTFs) and of bone marrow-derived stem cells genetically engineered to overexpress those neurotrophic factors (NTF-BMSCs). The neurite outgrowth inductive activity was monitored in culture systems of adult and neonatal rat sensory dorsal root ganglion neurons as well as in the cell line from rat pheochromocytoma (PC-12) cell sympathetic culture model system. Results We demonstrate that np-NTFs reliably support numeric neurite outgrowth in all utilized culture models. In some aspects, especially with regard to their long-term bioactivity, np-NTFs are even superior to free NTFs. Engineered NTF-BMSCs proved to be less effective in induction of sensory neurite outgrowth but demonstrated an increased bioactivity in the PC-12 cell culture system. In contrast, primary nontransfected BMSCs were as effective as np-NTFs in sensory neurite induction and demonstrated an impairment of neuronal differentiation in the PC-12 cell system. Conclusion Our results evidence that nanotechnology as used in our setup is superior over stem cell engineering when it comes to in vitro models for PNR. Furthermore, np-NTFs can easily be suspended in regenerative hydrogel matrix and could be delivered that way to nerve conduits for future in vivo studies and medical application.