TY - JOUR A1 - Deininger, Christian A1 - Wagner, Andrea A1 - Heimel, Patrick A1 - Salzer, Elias A1 - Monforte Vila, Xavier A1 - Weißenbacher, Nadja A1 - Grillari, Johannes A1 - Redl, Heinz A1 - Wichlas, Florian A1 - Freude, Thomas A1 - Tempfer, Herbert A1 - Teuschl-Woller, Andreas A1 - Traweger, Andreas T1 - Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite JF - Int. J. Mol. Sci. N2 - The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing. KW - Tissue Engineering KW - Biomaterials KW - silk scaffold KW - bone regeneration KW - pseudoarthrosis Y1 - VL - 23 IS - 1 / 283 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 - Teuschl, Andreas A1 - Tangl, Stefan A1 - Heimel, Patrick A1 - Schwarze, Uwe Yacine A1 - Monforte, Xavier A1 - Redl, Heinz A1 - Nau, Thomas T1 - Osteointegration of a Novel Silk Fiber-Based ACL Scaffold by Formation of a Ligament-Bone Interface. JF - American Journal of Sports Medicine KW - Tissue Engineering KW - Silk KW - Scaffold KW - ACL Y1 - ER - TY - GEN A1 - Teuschl, Andreas A1 - Heimel, Patrick A1 - Monforte Vila, Xavier A1 - Nürnberger, Sylvia A1 - Tangl, Stefan A1 - van Griensven, Martijn A1 - Redl, Heinz A1 - Nau, Thomas T1 - Anterior cruciate ligament regeneration using the silk-based RegACL scaffold KW - Tissue Engineering KW - Silk KW - Biomaterial KW - Anterior Cruciate Ligament Y1 - 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 - Schneider, Cornelia A1 - Lehmann, Johannes A1 - van Osch, Gerjo A1 - Hildner, Florian A1 - Teuschl, Andreas A1 - Monforte Vila, Xavier A1 - Miosga, David A1 - Heimel, Patrick A1 - Priglinger, Eleni A1 - Redl, Heinz A1 - Wolbank, Susanne A1 - Nürnberger, Sylvia T1 - Systematic Comparison of Protocols for the Preparation of Human Articular Cartilage for Use as Scaffold Material in Cartilage Tissue Engineering JF - Tissue Eng Part C Methods KW - Cartilage KW - Scaffold Material Y1 - 2018 VL - 22 IS - 12 ER - TY - GEN A1 - Teuschl, Andreas A1 - Fuchs, Christiane A1 - Weihs, Anna A1 - Heimel, Patrick A1 - Rünzler, Dominik A1 - Redl, Heinz A1 - Nau, Thomas T1 - The Silk Road from Textiles to Novel Medical Implants KW - Silk Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Heimel, Patrick A1 - Nürnberger, Sylvia A1 - Redl, Heinz A1 - Nau, Thomas T1 - ACL Regeneration using a novel silk fiber based scaffold - Histological Results of a Large Animal Study KW - Tissue Regeneration KW - Silk KW - Scaffold Y1 - 2018 ER - TY - JOUR A1 - Teuschl, Andreas A1 - Heimel, Patrick A1 - Nürnberger, Sylvia A1 - van Griensven, Martijn A1 - Redl, Heinz A1 - Nau, Thomas T1 - A Novel Silk Fiber-Based Scaffold for Regeneration of the Anterior Cruciate Ligament: Histological Results From a Study in Sheep. JF - The American Journal of Sports Medicine KW - Ligament KW - Regeneration Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Fuchs, Christiane A1 - Feichtinger, Georg A1 - Heher, Philipp A1 - Heimel, Patrick A1 - Schuh, Christina A1 - Nürnberger, Sylvia A1 - Nau, Thomas A1 - Rünzler, Dominik A1 - Redl, Heinz T1 - Fibrin or Fibroin - Not only the "o" Makes the Difference KW - Fibrin KW - Fibroin Y1 - 2018 ER - TY - GEN A1 - Teuschl, Andreas A1 - Nürnberger, Sylvia A1 - Heimel, Patrick A1 - Redl, Heinz A1 - Nau, Thomas T1 - Regeneration of the Anterior Cruciate Ligament Using a Silk-Fiber Based Scaffold - Histological Results KW - Tissue Regeneration KW - Ligaments KW - Scaffold Y1 - 2018 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 - 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 - Bernhard, Jonathan C A1 - Marolt Presen, Darja A1 - Li, Ming A1 - Monforte, Xavier A1 - Ferguson, James A1 - Leinfellner, Gabriele A1 - Heimel, Patrick A1 - Betti, Susanne L A1 - Shu, Sharon A1 - Teuschl-Woller, Andreas H A1 - Tangl, Stefan A1 - Redl, Heinz A1 - Vunjak-Novakovic, Gordana T1 - Effects of Endochondral and Intramembranous Ossification Pathways on Bone Tissue Formation and Vascularization in Human Tissue-Engineered Grafts JF - Cells N2 - Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds into either hypertrophic chondrocytes (hyper) or osteoblasts (osteo) over 5 weeks of in vitro cultivation, and were implanted subcutaneously for 12 weeks. The pathways' constructs were evaluated over time with respect to gene expression, composition, histomorphology, microstructure, vascularization and biomechanics. Hypertrophic chondrocytes expressed higher levels of osteogenic genes and deposited significantly more bone mineral and proteins than the osteoblasts. Before implantation, the mineral in the hyper group was less mature than that in the osteo group. Following 12 weeks of implantation, the hyper group had increased mineral density but a similar overall mineral composition compared with the osteo group. The hyper group also displayed significantly more blood vessel infiltration than the osteo group. Both groups contained M2 macrophages, indicating bone regeneration. These data suggest that, similar to the body's repair processes, endochondral pathway might be more advantageous when regenerating large defects, whereas intramembranous ossification could be utilized to guide the tissue formation pattern with a scaffold architecture. KW - bone tissue engineering KW - endochondral KW - mesenchymal stromal cells KW - ossification KW - intramembranous Y1 - U6 - http://dx.doi.org/10.3390/cells11193070 VL - 11 IS - 19:3070 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 -