@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{FarokhiAleemardaniSolouketal.,
  author    = {Farokhi, Maryam and Aleemardani, Mina and Solouk, Atefeh and Mirzadeh, Hamid and Teuschl, Andreas Herbert and Redl, Heinz},
  title     = {Crosslinking strategies for silk fibroin hydrogels: promising biomedical materials},
  series = {Biomedical Materials},
  volume    = {16},
  journal   = {Biomedical Materials},
  number    = {2},
  pages     = {022004},
  abstract  = {Due to their strong biomimetic potential, silk fibroin (SF) hydrogels are impressive candidates for tissue engineering, due to their tunable mechanical properties, biocompatibility, low immunotoxicity, controllable biodegradability, and a remarkable capacity for biomaterial modification and the realization of a specific molecular structure. The fundamental chemical and physical structure of SF allows its structure to be altered using various crosslinking strategies. The established crosslinking methods enable the formation of three-dimensional (3D) networks under physiological conditions. There are different chemical and physical crosslinking mechanisms available for the generation of SF hydrogels (SFHs). These methods, either chemical or physical, change the structure of SF and improve its mechanical stability, although each method has its advantages and disadvantages. While chemical crosslinking agents guarantee the mechanical strength of SFH through the generation of covalent bonds, they could cause some toxicity, and their usage is not compatible with a cell-friendly technology. On the other hand, physical crosslinking approaches have been implemented in the absence of chemical solvents by the induction of β-sheet conformation in the SF structure. Unfortunately, it is not easy to control the shape and properties of SFHs when using this method. The current review discusses the different crosslinking mechanisms of SFH in detail, in order to support the development of engineered SFHs for biomedical applications.},
  subject      = {Tissue Engineering},
  language  = {en}
}
@article{NuernbergerSchneiderKeibletal.,
  author    = {N{\"u}rnberger, S. and Schneider, C. and Keibl, C. and Sch{\"a}dl, Barbara and Heimel, P. and Monforte, X. and Teuschl, A. H. and Nalbach, M. and Thurner, P. J. and Grillari, J. and Redl, Heinz and Wolbank, S.},
  title     = {Repopulation of decellularised articular cartilage by laser-based matrix engraving},
  series = {EBioMedicine.},
  volume    = {64},
  journal   = {EBioMedicine.},
  number    = {103196.},
  abstract  = {Background: In spite of advances in the treatment of cartilage defects using cell and scaffold-based therapeutic strategies, the long-term outcome is still not satisfying since clinical scores decline years after treatment. Scaffold materials currently used in clinical settings have shown limitations in providing suitable biomechanical properties and an authentic and protective environment for regenerative cells. To tackle this problem, we developed a scaffold material based on decellularised human articular cartilage. Methods: Human articular cartilage matrix was engraved using a CO2 laser and treated for decellularisation and glycosaminoglycan removal. Characterisation of the resulting scaffold was performed via mechanical testing, DNA and GAG quantification and in vitro cultivation with adipose-derived stromal cells (ASC). Cell vitality, adhesion and chondrogenic differentiation were assessed. An ectopic, unloaded mouse model was used for the assessment of the in vivo performance of the scaffold in combination with ASC and human as well as bovine chondrocytes. The novel scaffold was compared to a commercial collagen type I/III scaffold. Findings: Crossed line engravings of the matrix allowed for a most regular and ubiquitous distribution of cells and chemical as well as enzymatic matrix treatment was performed to increase cell adhesion. The biomechanical characteristics of this novel scaffold that we term CartiScaff were found to be superior to those of commercially available materials. Neo-tissue was integrated excellently into the scaffold matrix and new collagen fibres were guided by the laser incisions towards a vertical alignment, a typical feature of native cartilage important for nutrition and biomechanics. In an ectopic, unloaded in vivo model, chondrocytes and mesenchymal stromal cells differentiated within the incisions despite the lack of growth factors and load, indicating a strong chondrogenic microenvironment within the scaffold incisions. Cells, most noticeably bone marrow-derived cells, were able to repopulate the empty chondrocyte lacunae inside the scaffold matrix. Interpretation: Due to the better load-bearing, its chondrogenic effect and the ability to guide matrix-deposition, CartiScaff is a promising biomaterial to accelerate rehabilitation and to improve long term clinical success of cartilage defect treatment. Funding: Austrian Research Promotion Agency FFG ("CartiScaff" \#842455), Lorenz B{\"o}hler Fonds (16/13), City of Vienna Competence Team Project Signaltissue (MA23, \#18-08). Keywords: Cartilage regeneration; Decellularisation; Ectopic animal model; Laser engraving; Mechanical testing; Repopulation.},
  subject      = {Tissue Engineering},
  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{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}
}
@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}
}