TY - JOUR A1 - Feichtinger, Xaver A1 - Monforte, Xavier A1 - Keibl, Claudia A1 - Hercher, David A1 - Schanda, Jakob A1 - Teuschl, Andreas A1 - Muschitz, Christian A1 - Redl, Heinz A1 - Fialka, Christian A1 - Mittermayr, Rainer T1 - Substantial Biomechanical Improvement by Extracorporeal Shockwave Therapy After Surgical Repair of Rodent Chronic Rotator Cuff Tears. JF - American Journal of Sports Medicine KW - Shockwave Therapy KW - Tissue Engineering KW - Regeneration KW - Surgery Y1 - ER - TY - GEN A1 - Slezak, Paul A1 - Rose, Roland A1 - Hercher, David A1 - Weihs, Anna A1 - Fuchs, Christiane A1 - Redl, Heinz A1 - Mittermayr, Rainer A1 - Slezak, Cyrill T1 - Tracking therapeutic shockwaves and their impact on regeneration KW - Shockwave Therapy KW - Tissue Regeneration Y1 - ER - TY - JOUR A1 - Schuh, Christina A1 - Hercher, David A1 - Stainer, Michaela A1 - Hopf, Rudolf A1 - Teuschl, Andreas A1 - Schmidhammer, Robert A1 - Redl, Heinz T1 - Extracorporeal shockwave treatment: A novel tool to improve Schwann cell isolation and culture JF - Cytotherapy KW - Extracorporeal shockwave Y1 - 2018 ER - TY - JOUR A1 - Heinzel, Johannes Christoph A1 - Oberhauser, Viola A1 - Keibl, Claudia A1 - Schädl, Barbara A1 - Swiadek, Nicole V. A1 - Längle, Gregor A1 - Frick, Helen A1 - Slezak, Cyrill A1 - Prahm, Cosima A1 - Grillari, Johannes A1 - Kolbenschlag, Jonas A1 - Hercher, David T1 - ESWT Diminishes Axonal Regeneration following Repair of the Rat Median Nerve with Muscle-In-Vein Conduits but Not after Autologous Nerve Grafting JF - Biomedicines N2 - Investigations reporting positive effects of extracorporeal shockwave therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7 mm segment of the right median nerve was reconstructed either with an ANG or an MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. The animals were observed for 12 weeks, and nerve regeneration was assessed using computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here, we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair. KW - Tissue Engineering KW - Muscle-In-Vein Conduits KW - Axonal Regeneration KW - Autologous Nerve Grafting Y1 - VL - 2022 IS - 10(8) SP - 1777 ER - TY - JOUR A1 - Heimel, Patrick A1 - Swiadek, Nicole V. A1 - Slezak, Paul A1 - Kerbl, Markus A1 - Schneider, Cornelia A1 - Nürnberger, Sylvia A1 - Redl, Heinz A1 - Teuschl, Andreas A1 - Hercher, David T1 - Iodine-Enhanced Micro-CT Imaging of Soft Tissue on the Example of Peripheral Nerve Regeneration JF - Contrast Media & Molecular Imaging KW - µCT KW - Imaging KW - Tissue Engineering KW - Tissue Regeneration Y1 - ER - TY - JOUR A1 - Hromada, Carina A1 - Hartmann, Jaana A1 - Oesterreicher, Johannes A1 - Stoiber, Anton A1 - Daerr, Anna A1 - Schädl, Barbara A1 - Priglinger, Eleni A1 - Teuschl-Woller, Andreas H. A1 - Holnthoner, Wolfgang A1 - Heinzel, Johannes Christoph A1 - Hercher, David T1 - Occurrence of Lymphangiogenesis in Peripheral Nerve Autografts Contrasts Schwann Cell-Induced Apoptosis of Lymphatic Endothelial Cells In Vitro JF - Biomolecules N2 - Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in cases of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly under-investigated. In this study, we analyzed the presence of lymphatic vasculature in healthy and regenerated murine peripheral nerves, revealing that nerve autografts contained increased numbers of lymphatic vessels after segmental damage. This led us to elucidate the interaction between lymphatic endothelial cells (LECs) and Schwann cells (SCs) in vitro. We show that SC and LEC secretomes did not influence the respective other cell types' migration and proliferation in 2D scratch assay experiments. Furthermore, we successfully created lymphatic microvascular structures in SC-embedded 3D fibrin hydrogels, in the presence of supporting cells; whereas SCs seemed to exert anti-lymphangiogenic effects when cultured with LECs alone. Here, we describe, for the first time, increased lymphangiogenesis after peripheral nerve injury and repair. Furthermore, our findings indicate a potential lymph-repellent property of SCs, thereby providing a possible explanation for the lack of lymphatic vessels in the healthy endoneurium. Our results highlight the importance of elucidating the molecular mechanisms of SC-LEC interaction. KW - Tissue Engineering KW - peripheral nerve regeneration KW - lymphangiogenesis KW - Schwann cells KW - lymphatic endothelial cells Y1 - VL - 2022 IS - 12, 6 SP - 820 ER - TY - JOUR A1 - Lauer, Henrik A1 - Prahm, Cosima A1 - Thiel, Johannes Tobias A1 - Kolbenschlag, Jonas A1 - Daigeler, Adrien A1 - Hercher, David A1 - Heinzel, Johannes Christoph T1 - The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury JF - Biomedicines N2 - The rat median nerve model is a well-established and frequently used model for peripheral nerve injury and repair. The grasping test is the gold-standard to evaluate functional recovery in this model. However, no comprehensive review exists to summarize the course of functional recovery in regard to the lesion type. According to PRISMA-guidelines, research was performed, including the databases PubMed and Web of Science. Groups were: (1) crush injury, (2) transection with end-to-end or with (3) end-to-side coaptation and (4) isogenic or acellular allogenic grafting. Total and respective number, as well as rat strain, type of nerve defect, length of isogenic or acellular allogenic allografts, time at first signs of motor recovery (FSR) and maximal recovery grasping strength (MRGS), were evaluated. In total, 47 articles met the inclusion criteria. Group I showed earliest signs of motor recovery. Slow recovery was observable in group III and in graft length above 25 mm. Isografts recovered faster compared to other grafts. The onset and course of recovery is heavily dependent from the type of nerve injury. The grasping test should be used complementary in addition to other volitional and non-volitional tests. Repetitive examinations should be planned carefully to optimize assessment of valid and reliable data. KW - Tissue Engineering KW - Median Nerve Injury KW - Nerve Regeneration Y1 - VL - 2022 IS - 10(8) SP - 1878 ER - TY - JOUR A1 - Ashmwe, Mohamed A1 - Posa, Katja A1 - Rührnößl, Alexander A1 - Heinzel, Johannes Christoph A1 - Heimel, Patrick A1 - Mock, Michael A1 - Schädl, Barbara A1 - Keibl, Claudia A1 - Couillard-Despres, Sebastien A1 - Redl, Heinz A1 - Mittermayr, Rainer A1 - Hercher, David T1 - Effects of Extracorporeal Shockwave Therapy on Functional Recovery and Circulating miR-375 and miR-382-5p after Subacute and Chronic Spinal Cord Contusion Injury in Rats JF - Biomedicines N2 - Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT-applied within the subacute and chronic phase of SCI (spinal cord injury) on recovery in a rat spinal cord contusion model. Outcomes were evaluated by gait analysis, µCT and histological analysis of spinal cords. A panel of serum-derived miRNAs after SCI and after ESWT was investigated to identify injury-, regeneration- and treatment-associated expression patterns. Rats receiving ESWT showed significant improvement in motor function in both a subacute and a chronic experimental setting. This effect was not reflected in changes in morphology, µCT-parameters or histological markers after ESWT. Expression analysis of various miRNAs, however, revealed changes after SCI and ESWT, with increased miR-375, indicating a neuroprotective effect, and decreased miR-382-5p potentially improving neuroplasticity via its regulatory involvement with BDNF. We were able to demonstrate a functional improvement of ESWT-treated animals after SCI in a subacute and chronic setting. Furthermore, the identification of miR-375 and miR-382-5p could potentially provide new targets for therapeutic intervention in future studies. KW - Tissue Engineering KW - ESWT KW - Spinal Cord Injury Y1 - U6 - http://dx.doi.org/https://doi.org/10.3390/biomedicines10071630 VL - 2022 IS - 10(7) SP - 1630 ER - TY - JOUR A1 - Romanelli, Pasquale A1 - Bieler, Lara A1 - Heimel, Patrick A1 - Škokić, Siniša A1 - Jakubecova, Dominika A1 - Kreutzer, Christina A1 - Zaunmair, Pia A1 - Smolčić, Tomislav A1 - Benedetti, Bruno A1 - Rohde, Eva A1 - Gimona, Mario A1 - Hercher, David A1 - Dobrivojević Radmilović, Marina A1 - Couillard-Despres, Sebastien T1 - Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury JF - Front Cell Neurosci N2 - Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion. KW - exosomes KW - inflammation KW - locomotion KW - neuroimaging KW - motor function Y1 - U6 - http://dx.doi.org/10.3389/fncel.2021.795008 VL - 15 ER - TY - JOUR A1 - Feichtinger, Xaver A1 - Heimel, Patrick A1 - Tangl, Stefan A1 - Keibl, Claudia A1 - Nürnberger, Sylvia A1 - Schanda, Jakob Emanuel A1 - Hercher, David A1 - Kocijan, Roland A1 - Redl, Heinz A1 - Grillari, Johannes A1 - Fialka, Christian A1 - Mittermayr, Rainer T1 - Improved biomechanics in experimental chronic rotator cuff repair after shockwaves is not reflected by bone microarchitecture JF - PLoS One KW - chronic rotator cuff repair KW - bone microarchitecture Y1 - U6 - http://dx.doi.org/10.1371/journal.pone.0262294 VL - 17 IS - 1 ER -