@article{PriglingerSchuhSteffenhagenetal., author = {Priglinger, Eleni and Schuh, Christina and Steffenhagen, Carolin and Wurzer, Christoph and Maier, Julia and N{\"u}rnberger, Sylvia and Holnthoner, Wolfgang and Fuchs, Christiane and Suessner, Susanne and R{\"u}nzler, Dominik and Redl, Heinz and Wolbank, Susanne}, title = {Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.}, series = {Cytotherapy}, journal = {Cytotherapy}, pages = {1079 -- 1095}, abstract = {BACKGROUND: Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. METHODS: In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. RESULTS: After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. DISCUSSION: Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation.}, subject = {Shockwave Therapy}, language = {en} } @article{BachmannSpitzRothbaueretal., author = {Bachmann, Barbara and Spitz, Sarah and Rothbauer, Mario and Jordan, Christian and Purtscher, Michaela and Zirath, Helene and Schuller, Patrick and Eilenberger, Christoph and Ali, Syed Faheem and M{\"u}hleder, Severin and Priglinger, Eleni and Harasek, Michael and Redl, Heinz and Holnthoner, Wolfgang and Ertl, Peter}, title = {Engineering of three-dimensional pre-vascular networks within fibrin hydrogel constructs by microfluidic control over reciprocal cell signaling}, series = {Biomicrofluidics}, journal = {Biomicrofluidics}, subject = {Microfluidic}, language = {en} } @misc{SchneiderAignerMonforteVilaetal., author = {Schneider, Karl Heinrich and Aigner, Petra and Monforte Vila, Xavier and Holnthoner, Wolfgang and Teuschl, Andreas and Bergmeister, Helga and Redl, Heinz}, title = {Naturally derived acellular small diameter vascular grafts from human placenta for reconstructive surgery}, subject = {Placenta}, language = {en} } @article{SchneiderPultarOesterreicheretal., author = {Schneider, Jaana and Pultar, Marianne and Oesterreicher, Johannes and Bobbili, Madhusudhan Reddy and M{\"u}hleder, Severin and Priglinger, Eleni and Redl, Heinz and Spittler, Andreas and Grillari, Johannes and Holnthoner, Wolfgang}, title = {Cre mRNA Is Not Transferred by EVs from Endothelial and Adipose-Derived Stromal/Stem Cells during Vascular Network Formation}, series = {Int J Mol Sci.}, volume = {2021}, journal = {Int J Mol Sci.}, number = {22(8)}, pages = {4050}, abstract = {Coculture systems employing adipose tissue-derived mesenchymal stromal/stem cells (ASC) and endothelial cells (EC) represent a widely used technique to model vascularization. Within this system, cell-cell communication is crucial for the achievement of functional vascular network formation. Extracellular vesicles (EVs) have recently emerged as key players in cell communication by transferring bioactive molecules between cells. In this study we aimed to address the role of EVs in ASC/EC cocultures by discriminating between cells, which have received functional EV cargo from cells that have not. Therefore, we employed the Cre-loxP system, which is based on donor cells expressing the Cre recombinase, whose mRNA was previously shown to be packaged into EVs and reporter cells containing a construct of floxed dsRed upstream of the eGFP coding sequence. The evaluation of Cre induced color switch in the reporter system via EVs indicated that there is no EV-mediated RNA transmission either between EC themselves or EC and ASC. However, since Cre mRNA was not found present in EVs, it remains unclear if Cre mRNA is generally not packaged into EVs or if EVs are not taken up by the utilized cell types. Our data indicate that this technique may not be applicable to evaluate EV-mediated cell-to-cell communication in an in vitro setting using EC and ASC. Further investigations will require a functional system showing efficient and specific loading of Cre mRNA or protein into EVs.}, subject = {Tissue Engineering}, language = {en} } @article{NuernbergerSchneidervanOschetal., author = {N{\"u}rnberger, Sylvia and Schneider, Cornelia and van Osch, Gerjo and Keibl, Claudia and Rieder, Bernhard and Monforte, Xavier and Teuschl, Andreas and M{\"u}hleder, Severin and Holnthoner, Wolfgang and Sch{\"a}dl, Barbara and Gahleitner, Christoph and Redl, Heinz and Wolbank, Susanne}, title = {Repopulation of an auricular cartilage scaffold, AuriScaff, perforated with an enzyme combination.}, series = {Acta Biomaterialia}, journal = {Acta Biomaterialia}, subject = {Tissue Engineering}, language = {en} } @article{JohannesWeihsKarneretal., author = {Johannes, Hackethal and Weihs, Anna and Karner, Lisa and Metzger, Magdalena and Dungel, Peter and Hennerbichler, Simone and Redl, Heinz and Teuschl-Woller, Andreas Herbert}, title = {Novel Human Placenta-Based Extract for Vascularization Strategies in Tissue Engineering}, series = {Tissue Eng Part C Methods}, volume = {27}, journal = {Tissue Eng Part C Methods}, number = {11}, pages = {616 -- 632}, abstract = {There is critical unmet need for new vascularized tissues to support or replace injured tissues and organs. Various synthetic and natural materials were already established for use of two-dimensional (2D) and three-dimensional (3D) in vitro neovascularization assays, however, they still cannot mimic the complex functions of the sum of the extracellular matrix (ECM) in native intact tissue. Currently, this issue is only addressed by artificial products such as Matrigel™, which comprises a complex mixture of ECM proteins, extracted from animal tumor tissue. Despite its outstanding bioactivity, the isolation from tumor tissue hinders its translation into clinical applications. Since nonhuman ECM proteins may cause immune reactions, as are frequently observed in clinical trials, human ECM proteins represent the best option when aiming for clinical applications. Here, we describe an effective method of isolating a human placenta substrate (hpS) that induces the spontaneous formation of an interconnected network of green fluorescence-labeled human umbilical vein endothelial cells (gfpHUVECs) in vitro. The substrate was biochemically characterized by using a combination of bicinchoninic acid (BCA) assay, DNA, and glycosaminoglycan (GAG) content assays, sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis and Western blot, angiogenesis arrays, chromatographic thrombin detection, high performance liquid chromatography (HPLC)-based amino acid quantification analysis, and assessment of antimicrobial properties. 2D in vitro cell culture experiments have been performed to determine the vasculogenic potential of hpS, which demonstrated that cell networks developed on hpS show a significantly higher degree of complexity (number of tubules/junctions; total/mean tube length) when compared with Matrigel. As 3D cell culture techniques represent a more accurate representation of the in vivo condition, the substrate was 3D solidified using various natural polymers. 3D in vitro vasculogenesis assays have been performed by seeding gfpHUVECs in an hpS-fibrinogen clot. In conclusion, hpS provides a potent human/material-based alternative to xenogenic-material-based biomaterials for vascularization strategies in tissue engineering.}, subject = {Tissue Engineering}, language = {en} } @inproceedings{KneblMortonRedletal., author = {Knebl, Gerald and Morton, Tatjana J. and Redl, Heinz and R{\"u}nzler, Dominik}, title = {Mechanical stimulation of cells in 3-dimensional fibrin constructs using a bioreactor}, series = {3. Forschungsforum der {\"o}sterreichischen Fachhochschulen / Fachhochschule K{\"a}rnten}, booktitle = {3. Forschungsforum der {\"o}sterreichischen Fachhochschulen / Fachhochschule K{\"a}rnten}, pages = {492 -- 493}, subject = {Cells}, language = {en} } @article{SchneiderAignerHolnthoneretal., author = {Schneider, Karl Heinrich and Aigner, Petra and Holnthoner, Wolfgang and Monforte Vila, Xavier and N{\"u}rnberger, Sylvia and R{\"u}nzler, Dominik and Redl, Heinz and Teuschl, Andreas}, title = {Decellularized human placenta chorion matrix as a favorable source of small-diameter vascular grafts}, series = {Acta Biomaterialia}, journal = {Acta Biomaterialia}, subject = {Grafting}, 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{RohringerHolnthonerHackletal., author = {Rohringer, Sabrina and Holnthoner, Wolfgang and Hackl, Matthias and Weihs, Anna and R{\"u}nzler, Dominik and Skalicky, Susanna and Karbiener, Michael and Scheideler, Marcel and Pr{\"o}ll, Johannes and Gabriel, Christian and Schweighofer, Bernhard and Gr{\"o}ger, Marion and Spittler, Andreas and Grillari, Johannes and Redl, Heinz}, title = {Molecular and cellular effects of in vitro shockwave treatment on lymphatic endothelial cells.}, series = {PLoS one}, journal = {PLoS one}, subject = {Shockwave}, language = {en} } @article{RothbauerByrneSchobesbergeretal., author = {Rothbauer, Mario and Byrne, Ruth A. and Schobesberger, Silvia and Olmos Calvo, Isabel and Fischer, Anita and Reihs, Eva I. and Spitz, Sarah and Bachmann, Barbara and Sevelda, Florian and Holinka, Johannes and Holnthoner, Wolfgang and Redl, Heinz and Toegel, Stefan and Windhager, Reinhard and Kiener, Hans P. and Ertl, Peter}, title = {Establishment of a human three-dimensional chip-based chondro-synovial coculture joint model for reciprocal cross talk studies in arthritis research}, series = {Lab on a Chip}, volume = {2021}, journal = {Lab on a Chip}, number = {21}, pages = {4128 -- 4143}, abstract = {Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue coculture model that simulates the reciprocal cross talk between individual synovial and chondral organoids. When co-cultivated with synovial organoids, we could demonstrate that chondral organoids induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross talk in the modelling of arthritic diseases.}, 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} } @article{HanetsederLevstekTeuschlWolleretal., author = {Hanetseder, Dominik and Levstek, Tina and Teuschl-Woller, Andreas and Frank, Julia Katharina and Schaedl, Barbara and Redl, Heinz and Marolt Presen, Darja}, title = {Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age}, series = {Front Bioeng Biotechnol}, volume = {11}, journal = {Front Bioeng Biotechnol}, doi = {https://doi.org/10.3389/fbioe.2023.1214019}, abstract = {Regeneration of bone defects is often limited due to compromised bone tissue physiology. Previous studies suggest that engineered extracellular matrices enhance the regenerative capacity of mesenchymal stromal cells. In this study, we used human-induced pluripotent stem cells, a scalable source of young mesenchymal progenitors (hiPSC-MPs), to generate extracellular matrix (iECM) and test its effects on the osteogenic capacity of human bone-marrow mesenchymal stromal cells (BMSCs). iECM was deposited as a layer on cell culture dishes and into three-dimensional (3D) silk-based spongy scaffolds. After decellularization, iECM maintained inherent structural proteins including collagens, fibronectin and laminin, and contained minimal residual DNA. Young adult and aged BMSCs cultured on the iECM layer in osteogenic medium exhibited a significant increase in proliferation, osteogenic marker expression, and mineralization as compared to tissue culture plastic. With BMSCs from aged donors, matrix mineralization was only detected when cultured on iECM, but not on tissue culture plastic. When cultured in 3D iECM/silk scaffolds, BMSCs exhibited significantly increased osteogenic gene expression levels and bone matrix deposition. iECM layer showed a similar enhancement of aged BMSC proliferation, osteogenic gene expression, and mineralization compared with extracellular matrix layers derived from young adult or aged BMSCs. However, iECM increased osteogenic differentiation and decreased adipocyte formation compared with single protein substrates including collagen and fibronectin. Together, our data suggest that the microenvironment comprised of iECM can enhance the osteogenic activity of BMSCs, providing a bioactive and scalable biomaterial strategy for enhancing bone regeneration in patients with delayed or failed bone healing.}, subject = {aging}, 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{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} }