@article{HeinzelOberhauserKeibletal., author = {Heinzel, Johannes Christoph and Oberhauser, Viola and Keibl, Claudia and Sch{\"a}dl, Barbara and Swiadek, Nicole V. and L{\"a}ngle, Gregor and Frick, Helen and Slezak, Cyrill and Prahm, Cosima and Grillari, Johannes and Kolbenschlag, Jonas and Hercher, David}, title = {ESWT Diminishes Axonal Regeneration following Repair of the Rat Median Nerve with Muscle-In-Vein Conduits but Not after Autologous Nerve Grafting}, series = {Biomedicines}, volume = {2022}, journal = {Biomedicines}, number = {10(8)}, pages = {1777}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} } @article{HromadaHartmannOesterreicheretal., author = {Hromada, Carina and Hartmann, Jaana and Oesterreicher, Johannes and Stoiber, Anton and Daerr, Anna and Sch{\"a}dl, Barbara and Priglinger, Eleni and Teuschl-Woller, Andreas H. and Holnthoner, Wolfgang and Heinzel, Johannes Christoph and Hercher, David}, title = {Occurrence of Lymphangiogenesis in Peripheral Nerve Autografts Contrasts Schwann Cell-Induced Apoptosis of Lymphatic Endothelial Cells In Vitro}, series = {Biomolecules}, volume = {2022}, journal = {Biomolecules}, number = {12, 6}, pages = {820}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} } @article{LauerPrahmThieletal., author = {Lauer, Henrik and Prahm, Cosima and Thiel, Johannes Tobias and Kolbenschlag, Jonas and Daigeler, Adrien and Hercher, David and Heinzel, Johannes Christoph}, title = {The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury}, series = {Biomedicines}, volume = {2022}, journal = {Biomedicines}, number = {10(8)}, pages = {1878}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} } @article{AshmwePosaRuehrnoessletal., author = {Ashmwe, Mohamed and Posa, Katja and R{\"u}hrn{\"o}ßl, Alexander and Heinzel, Johannes Christoph and Heimel, Patrick and Mock, Michael and Sch{\"a}dl, Barbara and Keibl, Claudia and Couillard-Despres, Sebastien and Redl, Heinz and Mittermayr, Rainer and Hercher, David}, title = {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}, series = {Biomedicines}, volume = {2022}, journal = {Biomedicines}, number = {10(7)}, doi = {https://doi.org/10.3390/biomedicines10071630}, pages = {1630}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} }