TY - JOUR A1 - Maleiner, Babette A1 - Tomasch, Janine A1 - Heher, Philipp A1 - Spadiut, Oliver A1 - Rünzler, Dominik A1 - Fuchs, Christiane T1 - The Importance of Biophysical and Biochemical Stimuli in Dynamic Skeletal Muscle Models. JF - Frontiers in Physiology N2 - Classical approaches to engineer skeletal muscle tissue based on current regenerative and surgical procedures still do not meet the desired outcome for patient applications. Besides the evident need to create functional skeletal muscle tissue for the repair of volumetric muscle defects, there is also growing demand for platforms to study muscle-related diseases, such as muscular dystrophies or sarcopenia. Currently, numerous studies exist that have employed a variety of biomaterials, cell types and strategies for maturation of skeletal muscle tissue in 2D and 3D environments. However, researchers are just at the beginning of understanding the impact of different culture settings and their biochemical (growth factors and chemical changes) and biophysical cues (mechanical properties) on myogenesis. With this review we intend to emphasize the need for new in vitro skeletal muscle (disease) models to better recapitulate important structural and functional aspects of muscle development. We highlight the importance of choosing appropriate system components, e.g., cell and biomaterial type, structural and mechanical matrix properties or culture format, and how understanding their interplay will enable researchers to create optimized platforms to investigate myogenesis in healthy and diseased tissue. Thus, we aim to deliver guidelines for experimental designs to allow estimation of the potential influence of the selected skeletal muscle tissue engineering setup on the myogenic outcome prior to their implementation. Moreover, we offer a workflow to facilitate identifying and selecting different analytical tools to demonstrate the successful creation of functional skeletal muscle tissue. Ultimately, a refinement of existing strategies will lead to further progression in understanding important aspects of muscle diseases, muscle aging and muscle regeneration to improve quality of life of patients and enable the establishment of new treatment options. KW - Bioreactor KW - Muscle KW - Biomaterial Y1 - ER - TY - JOUR A1 - Kuba, Markus T1 - A Note on the generating function of p-Bernoulli numbers JF - Quaestiones Mathematicae KW - Mathematics Y1 - ER - TY - JOUR A1 - Teschl, Susanne A1 - Unterkofler, Karl A1 - Mochalski, Pawel A1 - Teschl, Gerald A1 - Ager, C. A1 - Mayhew, C.A. A1 - King, Julian T1 - Modeling-based determination of physiological parameters of systemic VOCs by breath gas analysis, part 2. JF - Journal of Breath Research KW - Breath KW - Gas KW - Analysis Y1 - VL - 12 ER - TY - JOUR A1 - Schanda, Jakob A1 - Keibl, Claudia A1 - Heimel, Patrick A1 - Monforte, Xavier A1 - Feichtinger, Xaver A1 - Teuschl, Andreas A1 - Baierl, Andreas A1 - Muschitz, Christian A1 - Redl, Heinz A1 - Fialka, Christian A1 - Mittermayr, Rainer T1 - Zoledronic Acid Substantially Improves Bone Microarchitecture and Biomechanical Properties After Rotator Cuff Repair in a Rodent Chronic Defect Model JF - Am J Sports Med N2 - Background: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. Hypothesis: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. Study design: Controlled laboratory study. Methods: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro-computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. Results: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head (P = .005) and the medial humeral head (P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head (P = .004) and the medial humeral head (P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group (P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group (r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. Conclusion: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. Clinical relevance: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations. KW - Tissue Engineering KW - Rotator Cuff Tears Y1 - VL - 2020 Jul IS - 48 (9) SP - 2151 EP - 2160 ER - TY - JOUR A1 - Slezak, Paul A1 - Slezak, Cyrill A1 - Hartinger, Joachim A1 - Teuschl, Andreas A1 - Nürnberger, Sylvia A1 - Redl, Heinz A1 - Mittermayr, Rainer T1 - A Low Cost Implantation Model in the Rat That Allows a Spatial Assessment of Angiogenesis. JF - Frontiers in Bioengineering and Biotechnology N2 - There is continual demand for animal models that allow a quantitative assessment of angiogenic properties of biomaterials, therapies, and pharmaceuticals. In its simplest form, this is done by subcutaneous material implantation and subsequent vessel counting which usually omits spatial data. We have refined an implantation model and paired it with a computational analytic routine which outputs not only vessel count but also vessel density, distribution, and vessel penetration depth, that relies on a centric vessel as a reference point. We have successfully validated our model by characterizing the angiogenic potential of a fibrin matrix in conjunction with recombinant human vascular endothelial growth factor (rhVEGF165). The inferior epigastric vascular pedicles of rats were sheathed with silicone tubes, which were subsequently filled with 0.2 ml of fibrin and different doses of rhVEGF165, centrically embedding the vessels. Over 4 weeks, tissue samples were harvested and subsequently immunohistologically stained and computationally analyzed. The model was able to detect variations over the angiogenic potentials of growth factor spiked fibrin matrices. Adding 20 ng of rhVEGF165 resulted in a significant increase in vasculature while 200 ng of rhVEGF165 did not improve vascular growth. Vascularized tissue volume increased during the first week and vascular density increased during the second week. Total vessel count increased significantly and exhibited a peak after 2 weeks which was followed by a resorption of vasculature by week 4. In summary, a simple implantation model to study in vivo vascularization with only a minimal workload attached was enhanced to include morphologic data of the emerging vascular tree. KW - Tissue Engineering KW - Bioreactor KW - Biomaterial Y1 - ER - TY - JOUR A1 - Berkovitch, Yulia A1 - Cohen, Talia A1 - Peled, Eli A1 - Schmidhammer, Robert A1 - Hildner, Florian A1 - Teuschl, Andreas A1 - Wolbank, Susanne A1 - Yelin, Dvir A1 - Redl, Heinz A1 - Seliktar, Dror T1 - Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration. JF - Journal of Tissue Engineering and Regenerative Medicine N2 - Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi-synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo-patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser-ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo-patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process. KW - Tissue Engineering KW - Biomaterials KW - Nerve Regeneration Y1 - SP - 1049 EP - 1061 ER - TY - JOUR A1 - Nau, Thomas A1 - Teuschl, Andreas A1 - Ebner, Anna A1 - Jung, Ilse A1 - Schenk, Christian T1 - Low revision rate and excellent outcome of primary ACL repair with a minimum follow-up of 5 years. JF - Muscle, ligaments and tendons Journal N2 - Introduction: Due to limitations of ACL reconstruction, primary ACL repair has recently regained research interest. Although abandoned in the past, primary repair with conservation of the original ligament demonstrates considerable advantages compared to reconstruction. We hypothesized that early repair, strictly limited to patients with a proximal ACL rupture and excellent tissue quality of the remaining ACL stump, would lead to equal revision rates and subjective outcomes as reported for ACL reconstruction after a minimum of 5 years. Methods: In this questionnaire study, patients who had a primary ACL repair between 2002 and 2009 were invited to participate. Besides any potential revision surgery, the Tegner activity scale and the Knee Injury and Osteoarthritis Outcome Score were included in the evaluation. Results: Out of 1912 patients who had ACL related surgery during the observation period, 221 (11.4%) had a primary ACL repair. 60 patients (61 knees) were available for follow-up. In 2/61 (3.3%) cases ACL revision surgery was performed and one patient had meniscus surgery of the affected side. The median Tegner activity scale was 6 (range, 3 to 10). The mean KOOS subscores were 88.8% (Function/Sports), 86.6% (Quality of life), 94.6 (Symptoms), 94.0 (Pain) and 97.0 (Activities of Daily Living). Conclusion: Primary ACL repair, strictly limited to proximal ruptures with good tissue quality leads to revision rates and subjective outcome comparable to ACL reconstruction. Level of evidence: IV. KW - Regeneration Y1 - SP - 185 EP - 190 ER - TY - JOUR A1 - Berkovitch, Yulia A1 - Cohen, Talia A1 - Peled, Eli A1 - Schmidhammer, Robert A1 - Hildner, Florian A1 - Teuschl, Andreas A1 - Wolbank, Susanne A1 - Yelin, Dvir A1 - Redl, Heinz A1 - Seliktar, Dror T1 - Hydrogel Composition and Laser Micro-Patterning to Regulate Sciatic Nerve Regeneration JF - Journal of Tissue Engineering and Regenerative Medicine KW - Micro-Patterning KW - Laser KW - Nerve Regeneration Y1 - 2018 VL - 12 IS - 4 ER - TY - JOUR A1 - Bernhard, Jonathan A1 - Ferguson, James A1 - Rieder, Bernhard A1 - Heimel, Patrick A1 - Nau, Thomas A1 - Tangl, Stefan A1 - Redl, Heinz A1 - Vunjak-Novakovic, Gordana T1 - Tissue-engineered hypertrophic chondrocyte grafts enhanced long bone repair biomaterials JF - Biomaterials KW - Grafting KW - Biomaterials Y1 - 2018 IS - 139 SP - 202 EP - 212 ER - TY - JOUR A1 - Heher, Philipp A1 - Maleiner, Babette A1 - Prüller, Johanna A1 - Teuschl, Andreas A1 - Kollmitzer, Josef A1 - Monforte Vila, Xavier A1 - Wolbank, Susanne A1 - Redl, Heinz A1 - Rünzler, Dominik A1 - Fuchs, Christiane T1 - A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain JF - Acta Biomaterialia KW - Bioreactor Y1 - ER -