@misc{KueenburgTeuschl,
  author    = {K{\"u}enburg, Bernhard and Teuschl, Andreas},
  title     = {Regenerative silk ligament: scale up and regulatory strategy of a textile engineered silk implant for tissue regeneration of injured human ACL (anterior cruciate ligament)},
  abstract  = {61 a93591 27-SY-1 Regenerative silk ligament: scale up and regulatory strategy of a textile engineered silk implant for tissue regeneration of injured human ACL (anterior cruciate ligament) Bernhard K{\"u}enburg，Andreas Teuschl MorphoMed, Austria In the USA around 370.000 annual ACL ruptures in the predominately young population (age 18-30) following sport injuries cause a lot of pain and long term troubles for the affected patients. The well established standard procedure of autologous tissue transplantation stabilizes the knee and allows sport activities after 9-12 months. However, harvest of autologous tissue such as patellar tendon or semitendinosus (the most frequently used autograft) weakens other body areas and long term data show an increased rate of arthroses (up to 50\% after 10 years) associated with ACL reconstructions. Based on numerous preclinical data and data from a 12-month sheep study the scale-up as well as regulatory approval process of a novel textile engineered silk implant as ACL graft have been initiated. It is planned to enter a clinical trial and strive for regulatory approval as a medical class 3 implant. The sheep data (1) have revealed an approximately 50\% degradation of the purified medical silk, which acts as scaffold for the regrowth of a new endogenous ligament. The formation of oriented collagenous tissue fibers including vascularization proves a ligament tissue regeneration for the first time. Scale-up and implementation of a commercial process require a defined set of specifications of commercial silkworm (Bombyx mori) silk, a biological raw material sourced from the textile industry as well as adequate analytical methods to characterize the depletion of sericin in the course of the production process. Based on first full scale samples, the defined biocompatibility program has to be executed, in the EU following the ISO requirements of the notified bodies, in the USA determined by the FDA. Upon submission of the full technical documentation as well as the biocompati-bility data, approval of a clinical trial can be achieved in order to demonstrate the clinical efficacy of the silk based ACL graft compared to the gold standard method in two different randomized groups. As primary endpoint the knee stability will be tested by an apparatus supported Lachmann test. In this study, besides the clinical benefit the patient safety is an important goal. The results of this study will be used for achievement of regulatory approval. References: 1) Teuschl A, Heimel P, N{\"u}rnberger S, van Griensven M, Redl H, Nau T. Am. J. Sports Med. 2016;44:1547-57. 2) Teuschl AH, van Griensven M, Redl H. Tissue Eng. Part C Methods. 2014;20:431-9.},
  subject      = {Biomaterial},
  language  = {en}
}
@article{TallianHerreroRollettStadleretal.,
  author    = {Tallian, Claudia and Herrero-Rollett, Alexandra and Stadler, Karina and Vielnascher, Robert and Wieland, Karin and Weihs, Anna and Pellis, Alessandro and Teuschl, Andreas and Lendl, Bernhard and Amenitsch, Heinz and Guebitz, Georg M.},
  title     = {Structural insights into pH-responsive drug release of self-assembling human serum albumin-silk fibroin nanocapsules.},
  series = {European Journal of Pharmaceutics and Biopharmaceutics},
  journal   = {European Journal of Pharmaceutics and Biopharmaceutics},
  abstract  = {Inflammation processes are associated with significant decreases in tissue or lysosomal pH from 7.4 to 4, a fact that argues for the application of pH-responsive drug delivery systems. However, for their design and optimization a full understanding of the release mechanism is crucial. In this study we investigated the pH-depending drug release mechanism and the influence of silk fibroin (SF) concentration and SF degradation degree of human serum albumin (HSA)-SF nanocapsules. Sonochemically produced nanocapsules were investigated regarding particle size, colloidal stability, protein encapsulation, thermal stability and drug loading properties. Particles of the monodisperse phase showed average hydrodynamic radii between 438 and 888 nm as measured by DLS and AFM and a zeta potential of -11.12 ± 3.27 mV. Together with DSC results this indicated the successful production of stable nanocapsules. ATR-FTIR analysis demonstrated that SF had a positive effect on particle formation and stability due to induced beta-sheet formation and enhanced crosslinking. The pH-responsive release was found to depend on the SF concentration. In in-vitro release studies, HSA-SF nanocapsules composed of 50\% SF showed an increased pH-responsive release for all tested model substances (Rhodamine B, Crystal Violet and Evans Blue) and methotrexate at the lowered pH of 4.5 to pH 5.4, while HSA capsules without SF did not show any pH-responsive drug release. Mechanistic studies using confocal laser scanning microscopy (CLSM) and small angle X-ray scattering (SAXS) analyses showed that increases in particle porosity and decreases in particle densities are directly linked to pH-responsive release properties. Therefore, the pH-responsive release mechanism was identified as diffusion controlled in a novel and unique approach by linking scattering results with in vitro studies. Finally, cytotoxicity studies using the human monocytic THP-1 cell line indicated non-toxic behavior of the drug loaded nanocapsules when applied in a concentration of 62.5 µg mL-1.},
  subject      = {Biomaterial},
  language  = {en}
}
@article{SlezakSlezakHartingeretal.,
  author    = {Slezak, Paul and Slezak, Cyrill and Hartinger, Joachim and Teuschl, Andreas and N{\"u}rnberger, Sylvia and Redl, Heinz and Mittermayr, Rainer},
  title     = {A Low Cost Implantation Model in the Rat That Allows a Spatial Assessment of Angiogenesis.},
  series = {Frontiers in Bioengineering and Biotechnology},
  journal   = {Frontiers in Bioengineering and Biotechnology},
  abstract  = {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.},
  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}
}
@incollection{HackethalSchuhHoferetal.,
  author    = {Hackethal, Johannes and Schuh, Christina and Hofer, Alexandra and Meixner, Barbara and Hennerbichler, Simone and Redl, Heinz and Teuschl, Andreas},
  title     = {Human Placenta Laminin-111 as a Multifunctional Protein for Tissue Engineering and Regenerative Medicine},
  series = {Advances in Experimental Medicine and Biology},
  booktitle = {Advances in Experimental Medicine and Biology},
  publisher = {Springer},
  publisher      = {Fachhochschule Technikum Wien},
  subject      = {Biomaterial},
  language  = {en}
}
@article{SchneiderEnayatiGrasletal.,
  author    = {Schneider, Karl Heinrich and Enayati, Marjan and Grasl, Christian and Walter, Ingrid and Budinsky, Lubos and Zebic, Gabriel and Kaun, Christoph and Wagner, Anja and Kratochwill, Klaus and Redl, Heinz and Teuschl, Andreas and Podesser, Bruno K. and Bergmeister, Helga},
  title     = {Acellular vascular matrix grafts from human placenta chorion: Impact of ECM preservation on graft characteristics, protein composition and in vivo performance.},
  series = {Biomaterials},
  journal   = {Biomaterials},
  pages     = {14 -- 26},
  abstract  = {Small diameter vascular grafts from human placenta, decellularized with either Triton X-100 (Triton) or SDS and crosslinked with heparin were constructed and characterized. Graft biochemical properties, residual DNA, and protein composition were evaluated to compare the effect of the two detergents on graft matrix composition and structural alterations. Biocompatibility was tested in vitro by culturing the grafts with primary human macrophages and in vivo by subcutaneous implantation of graft conduits (n = 7 per group) into the flanks of nude rats. Subsequently, graft performance was evaluated using an aortic implantation model in Sprague Dawley rats (one month, n = 14). In situ graft imaging was performed using MRI angiography. Retrieved specimens were analyzed by electromyography, scanning electron microscopy, histology and immunohistochemistry to evaluate cell migration and the degree of functional tissue remodeling. Both decellularization methods resulted in grafts of excellent biocompatibility in vitro and in vivo, with low immunogenic potential. Proteomic data revealed removal of cytoplasmic proteins with relative enrichment of ECM proteins in decelluarized specimens of both groups. Noteworthy, LC-Mass Spectrometry analysis revealed that 16 proteins were exclusively preserved in Triton decellularized specimens in comparison to SDS-treated specimens. Aortic grafts showed high patency rates, no signs of thrombus formation, aneurysms or rupture. Conduits of both groups revealed tissue-specific cell migration indicative of functional remodeling. This study strongly suggests that decellularized allogenic grafts from the human placenta have the potential to be used as vascular replacement materials. Both detergents produced grafts with low residual immunogenicity and appropriate mechanical properties. Observed differences in graft characteristics due to preservation method had no impact on successful in vivo performance in the rodent model.},
  subject      = {Biomaterial},
  language  = {en}
}