@article{DeiningerWagnerHeimeletal., author = {Deininger, Christian and Wagner, Andrea and Heimel, Patrick and Salzer, Elias and Monforte Vila, Xavier and Weißenbacher, Nadja and Grillari, Johannes and Redl, Heinz and Wichlas, Florian and Freude, Thomas and Tempfer, Herbert and Teuschl-Woller, Andreas and Traweger, Andreas}, title = {Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite}, series = {Int. J. Mol. Sci.}, volume = {23}, journal = {Int. J. Mol. Sci.}, number = {1 / 283}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} } @article{SchandaKeiblHeimeletal., author = {Schanda, Jakob and Keibl, Claudia and Heimel, Patrick and Monforte, Xavier and Feichtinger, Xaver and Teuschl, Andreas and Baierl, Andreas and Muschitz, Christian and Redl, Heinz and Fialka, Christian and Mittermayr, Rainer}, title = {Zoledronic Acid Substantially Improves Bone Microarchitecture and Biomechanical Properties After Rotator Cuff Repair in a Rodent Chronic Defect Model}, series = {Am J Sports Med}, volume = {2020 Jul}, journal = {Am J Sports Med}, number = {48 (9)}, pages = {2151 -- 2160}, abstract = {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.}, subject = {Tissue Engineering}, language = {en} } @article{TeuschlTanglHeimeletal., author = {Teuschl, Andreas and Tangl, Stefan and Heimel, Patrick and Schwarze, Uwe Yacine and Monforte, Xavier and Redl, Heinz and Nau, Thomas}, title = {Osteointegration of a Novel Silk Fiber-Based ACL Scaffold by Formation of a Ligament-Bone Interface.}, series = {American Journal of Sports Medicine}, journal = {American Journal of Sports Medicine}, subject = {Tissue Engineering}, language = {en} } @misc{TeuschlHeimelMonforteVilaetal., author = {Teuschl, Andreas and Heimel, Patrick and Monforte Vila, Xavier and N{\"u}rnberger, Sylvia and Tangl, Stefan and van Griensven, Martijn and Redl, Heinz and Nau, Thomas}, title = {Anterior cruciate ligament regeneration using the silk-based RegACL scaffold}, subject = {Tissue Engineering}, language = {en} } @article{BernhardFergusonRiederetal., author = {Bernhard, Jonathan and Ferguson, James and Rieder, Bernhard and Heimel, Patrick and Nau, Thomas and Tangl, Stefan and Redl, Heinz and Vunjak-Novakovic, Gordana}, title = {Tissue-engineered hypertrophic chondrocyte grafts enhanced long bone repair biomaterials}, series = {Biomaterials}, journal = {Biomaterials}, number = {139}, pages = {202 -- 212}, subject = {Grafting}, language = {en} } @article{SchneiderLehmannvanOschetal., author = {Schneider, Cornelia and Lehmann, Johannes and van Osch, Gerjo and Hildner, Florian and Teuschl, Andreas and Monforte Vila, Xavier and Miosga, David and Heimel, Patrick and Priglinger, Eleni and Redl, Heinz and Wolbank, Susanne and N{\"u}rnberger, Sylvia}, title = {Systematic Comparison of Protocols for the Preparation of Human Articular Cartilage for Use as Scaffold Material in Cartilage Tissue Engineering}, series = {Tissue Eng Part C Methods}, volume = {22}, journal = {Tissue Eng Part C Methods}, number = {12}, subject = {Cartilage}, language = {en} } @misc{TeuschlFuchsWeihsetal., author = {Teuschl, Andreas and Fuchs, Christiane and Weihs, Anna and Heimel, Patrick and R{\"u}nzler, Dominik and Redl, Heinz and Nau, Thomas}, title = {The Silk Road from Textiles to Novel Medical Implants}, subject = {Silk}, language = {en} } @misc{TeuschlHeimelNuernbergeretal., author = {Teuschl, Andreas and Heimel, Patrick and N{\"u}rnberger, Sylvia and Redl, Heinz and Nau, Thomas}, title = {ACL Regeneration using a novel silk fiber based scaffold - Histological Results of a Large Animal Study}, subject = {Tissue Regeneration}, language = {en} } @article{TeuschlHeimelNuernbergeretal., author = {Teuschl, Andreas and Heimel, Patrick and N{\"u}rnberger, Sylvia and van Griensven, Martijn and Redl, Heinz and Nau, Thomas}, title = {A Novel Silk Fiber-Based Scaffold for Regeneration of the Anterior Cruciate Ligament: Histological Results From a Study in Sheep.}, series = {The American Journal of Sports Medicine}, journal = {The American Journal of Sports Medicine}, subject = {Ligament}, language = {en} } @misc{TeuschlFuchsFeichtingeretal., author = {Teuschl, Andreas and Fuchs, Christiane and Feichtinger, Georg and Heher, Philipp and Heimel, Patrick and Schuh, Christina and N{\"u}rnberger, Sylvia and Nau, Thomas and R{\"u}nzler, Dominik and Redl, Heinz}, title = {Fibrin or Fibroin - Not only the "o" Makes the Difference}, subject = {Fibrin}, language = {en} } @misc{TeuschlNuernbergerHeimeletal., author = {Teuschl, Andreas and N{\"u}rnberger, Sylvia and Heimel, Patrick and Redl, Heinz and Nau, Thomas}, title = {Regeneration of the Anterior Cruciate Ligament Using a Silk-Fiber Based Scaffold - Histological Results}, subject = {Tissue Regeneration}, language = {en} } @article{HeimelSwiadekSlezaketal., author = {Heimel, Patrick and Swiadek, Nicole V. and Slezak, Paul and Kerbl, Markus and Schneider, Cornelia and N{\"u}rnberger, Sylvia and Redl, Heinz and Teuschl, Andreas and Hercher, David}, title = {Iodine-Enhanced Micro-CT Imaging of Soft Tissue on the Example of Peripheral Nerve Regeneration}, series = {Contrast Media \& Molecular Imaging}, journal = {Contrast Media \& Molecular Imaging}, subject = {µCT}, 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} } @article{BernhardMaroltPresenLietal., author = {Bernhard, Jonathan C and Marolt Presen, Darja and Li, Ming and Monforte, Xavier and Ferguson, James and Leinfellner, Gabriele and Heimel, Patrick and Betti, Susanne L and Shu, Sharon and Teuschl-Woller, Andreas H and Tangl, Stefan and Redl, Heinz and Vunjak-Novakovic, Gordana}, title = {Effects of Endochondral and Intramembranous Ossification Pathways on Bone Tissue Formation and Vascularization in Human Tissue-Engineered Grafts}, series = {Cells}, volume = {11}, journal = {Cells}, number = {19:3070}, doi = {10.3390/cells11193070}, abstract = {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.}, subject = {bone tissue engineering}, language = {en} } @article{RomanelliBielerHeimeletal., author = {Romanelli, Pasquale and Bieler, Lara and Heimel, Patrick and Škokić, Siniša and Jakubecova, Dominika and Kreutzer, Christina and Zaunmair, Pia and Smolčić, Tomislav and Benedetti, Bruno and Rohde, Eva and Gimona, Mario and Hercher, David and Dobrivojević Radmilović, Marina and Couillard-Despres, Sebastien}, title = {Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury}, series = {Front Cell Neurosci}, volume = {15}, journal = {Front Cell Neurosci}, doi = {10.3389/fncel.2021.795008}, abstract = {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.}, subject = {exosomes}, language = {en} } @article{FeichtingerHeimelTangletal., author = {Feichtinger, Xaver and Heimel, Patrick and Tangl, Stefan and Keibl, Claudia and N{\"u}rnberger, Sylvia and Schanda, Jakob Emanuel and Hercher, David and Kocijan, Roland and Redl, Heinz and Grillari, Johannes and Fialka, Christian and Mittermayr, Rainer}, title = {Improved biomechanics in experimental chronic rotator cuff repair after shockwaves is not reflected by bone microarchitecture}, series = {PLoS One}, volume = {17}, journal = {PLoS One}, number = {1}, doi = {10.1371/journal.pone.0262294}, subject = {chronic rotator cuff repair}, language = {en} }