@article{XuFahmyGarciaWesdorpetal.2023,
  author    = {Xu, Jietao and Fahmy-Garcia, Shorouk and Wesdorp, Marinus A. and Kops, Nicole and Forte, Lucia and De Luca, Claudio and Misciagna, Massimiliano Maraglino and Dolcini, Laura and Filardo, Giuseppe and Labbert{\´e}, Margot and Vanc{\´i}kov{\´a}, Karin and Kok, Joeri and van Rietbergen, Bert and Nickel, Joachim and Farrell, Eric and Brama, Pieter A. J. and van Osch, Gerjo J. V. M.},
  title     = {Effectiveness of BMP-2 and PDGF-BB adsorption onto a collagen/collagen-magnesium-hydroxyapatite scaffold in weight-bearing and non-weight-bearing osteochondral defect bone repair: in vitro, ex vivo and in vivo evaluation},
  series = {Journal of Functional Biomaterials},
  volume    = {14},
  journal   = {Journal of Functional Biomaterials},
  number    = {2},
  issn      = {2079-4983},
  doi       = {10.3390/jfb14020111},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304019},
  year      = {2023},
  abstract  = {Despite promising clinical results in osteochondral defect repair, a recently developed bi-layered collagen/collagen-magnesium-hydroxyapatite scaffold has demonstrated less optimal subchondral bone repair. This study aimed to improve the bone repair potential of this scaffold by adsorbing bone morphogenetic protein 2 (BMP-2) and/or platelet-derived growth factor-BB (PDGF-BB) onto said scaffold. The in vitro release kinetics of BMP-2/PDGF-BB demonstrated that PDGF-BB was burst released from the collagen-only layer, whereas BMP-2 was largely retained in both layers. Cell ingrowth was enhanced by BMP-2/PDFG-BB in a bovine osteochondral defect ex vivo model. In an in vivo semi-orthotopic athymic mouse model, adding BMP-2 or PDGF-BB increased tissue repair after four weeks. After eight weeks, most defects were filled with bone tissue. To further investigate the promising effect of BMP-2, a caprine bilateral stifle osteochondral defect model was used where defects were created in weight-bearing femoral condyle and non-weight-bearing trochlear groove locations. After six months, the adsorption of BMP-2 resulted in significantly less bone repair compared with scaffold-only in the femoral condyle defects and a trend to more bone repair in the trochlear groove. Overall, the adsorption of BMP-2 onto a Col/Col-Mg-HAp scaffold reduced bone formation in weight-bearing osteochondral defects, but not in non-weight-bearing osteochondral defects.},
  language  = {en}
}
@article{WaxmanStrzalkowskaWangetal.2023,
  author    = {Waxman, Susannah and Strzalkowska, Alicja and Wang, Chao and Loewen, Ralitsa and Dang, Yalong and Loewen, Nils A.},
  title     = {Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture},
  series = {Graefe's Archive for Clinical and Experimental Ophthalmology},
  volume    = {261},
  journal   = {Graefe's Archive for Clinical and Experimental Ophthalmology},
  number    = {5},
  doi       = {10.1007/s00417-022-05915-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323845},
  pages     = {1359-1368},
  year      = {2023},
  abstract  = {Background Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function. Methods Porcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology. Results Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead. Conclusion Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.},
  language  = {en}
}
@article{BotheDeubelHesseetal.2019,
  author    = {Bothe, Friederike and Deubel, Anne-Kathrin and Hesse, Eliane and Lotz, Benedict and Groll, J{\"u}rgen and Werner, Carsten and Richter, Wiltrud and Hagmann, Sebastien},
  title     = {Treatment of focal cartilage defects in minipigs with zonal chondrocyte/mesenchymal progenitor cell constructs},
  series = {International Journal of Molecular Sciences},
  volume    = {20},
  journal   = {International Journal of Molecular Sciences},
  number    = {3},
  issn      = {1422-0067},
  doi       = {10.3390/ijms20030653},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285118},
  year      = {2019},
  abstract  = {Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O'Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage.},
  language  = {en}
}
@article{AlHejailanWeigelSchuerleinetal.2022,
  author    = {Al-Hejailan, Reem and Weigel, Tobias and Sch{\"u}rlein, Sebastian and Berger, Constantin and Al-Mohanna, Futwan and Hansmann, Jan},
  title     = {Decellularization of full heart — optimizing the classical sodium-dodecyl-sulfate-based decellularization protocol},
  series = {Bioengineering},
  volume    = {9},
  journal   = {Bioengineering},
  number    = {4},
  issn      = {2306-5354},
  doi       = {10.3390/bioengineering9040147},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270781},
  year      = {2022},
  abstract  = {Compared to cell therapy, where cells are injected into a defect region, the treatment of heart infarction with cells seeded in a vascularized scaffold bears advantages, such as an immediate nutrient supply or a controllable and persistent localization of cells. For this purpose, decellularized native tissues are a preferable choice as they provide an in vivo-like microenvironment. However, the quality of such scaffolds strongly depends on the decellularization process. Therefore, two protocols based on sodium dodecyl sulfate or sodium deoxycholate were tailored and optimized for the decellularization of a porcine heart. The obtained scaffolds were tested for their applicability to generate vascularized cardiac patches. Decellularization with sodium dodecyl sulfate was found to be more suitable and resulted in scaffolds with a low amount of DNA, a highly preserved extracellular matrix composition, and structure shown by GAG quantification and immunohistochemistry. After seeding human endothelial cells into the vasculature, a coagulation assay demonstrated the functionality of the endothelial cells to minimize the clotting of blood. Human-induced pluripotent-stem-cell-derived cardiomyocytes in co-culture with fibroblasts and mesenchymal stem cells transferred the scaffold into a vascularized cardiac patch spontaneously contracting with a frequency of 25.61 ± 5.99 beats/min for over 16 weeks. The customized decellularization protocol based on sodium dodecyl sulfate renders a step towards a preclinical evaluation of the scaffolds.},
  language  = {en}
}
@phdthesis{Berger2023,
  author    = {Berger, Constantin},
  title     = {Influence of the pancreatic extracellular matrix on pancreatic differentiation of human induced pluripotent stem cells and establishment of 3D organ models},
  doi       = {10.25972/OPUS-24126},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241268},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Der Diabetes mellitus bezeichnet eine bislang unheilbare, metabolische Erkrankung, die mit schwerwiegenden Folgeerkrankungen einhergeht. Unter den potentiellen Strategien zur Heilung von Diabetes mellitus stellt die in vitro Generierung adulter β-Zellen des endokrinen Pankreas aus humanen induziert pluripotenten Stammzellen (hiPS) einen vielversprechenden Ansatz dar. Zwar erm{\"o}glichen bisherige Protokolle die Herstellung von Zellen mit einem β-Zell-{\"a}hnlichen Charakter, jedoch zeigen diese eine zun{\"a}chst eingeschr{\"a}nkte Funktion, die sich erst im Verlauf einer vollst{\"a}ndigen, durch Transplantation induzierten, Reifung der Zellen, normalisiert. Vorangegangene Studien zeigen, dass sich die Extrazellularmatrix (EZM) von Geweben positiv auf das {\"U}berleben und die Funktion adulter, isolierter Langerhans-Inseln des Pankreas auswirkt. Vor diesem Hintergrund stellt sich die Frage, ob Einfl{\"u}sse der organspezifischen EZM die finale Reifung in vitro hergestellter β-Zellen herbeif{\"u}hren k{\"o}nnen. Um diese Hypothese zu testen, wurde im Rahmen der vorliegenden Studie die Wirkung der pankreatischen EZM auf die in vitro Differenzierung von hiPS zu endokrinen Zellen des Pankreas untersucht sowie die Eignung der pankreatischen EZM zur Etablierung eines Organmodells des endokrinen Pankreas erprobt. Hierzu wurde zun{\"a}chst eine pankreasspezifische EZM-Tr{\"a}gerstruktur (PanMa) durch Dezellularisierung von Pankreaten des Schweins mittels Natriumdesoxycholat hergestellt. Die generierte PanMa wurde anhand (immun-) histologischer F{\"a}rbungen, Rasterelektronen-mikroskopie, Feststellung des DNA-Gehalts sowie durch Versuche zur Perfusion und Wiederbesiedelung mit Endothelzellen eingehend charakterisiert. Zudem wurde auf Basis der ermittelten Daten ein Bewertungssystem (PancScore) zur standardisierten Herstellung der PanMa entwickelt. Als N{\"a}chstes wurde untersucht, ob die PanMa {\"u}ber gewebespezifische EZM-Merkmale verf{\"u}gt. Zu diesem Zweck wurden biophysikalische und strukturelle Eigenschaften wie Festigkeit, Porosit{\"a}t und Hygroskopie mittels rheologischer Messungen sowie Versuchen zur Teilchendiffusion und zum Wasserbindungsverhalten bestimmt und mit azellul{\"a}ren EZMs des D{\"u}nndarms (SISser) und der Lunge (LungMa) verglichen. Nach der eingehenden Analyse der PanMa wurde deren Effekt auf die Eigenschaften von Stammzellen sowie auf fr{\"u}he Stadien der Stammzellentwicklung untersucht. Hierzu wurde die PanMa als Tr{\"a}gerstruktur w{\"a}hrend der Erhaltung sowie der spontanen Differenzierung von hiPS verwendet und der Einfluss der PanMa anhand von Genexpressionsanalysen und immunhistochemischer F{\"a}rbungen analysiert. In einem n{\"a}chsten Schritt wurde die Wirkung der PanMa auf die Differenzierung von hiPS zu endokrinen Zellen des Pankreas untersucht. Hierf{\"u}r wurde die PanMa zum einen in fl{\"u}ssiger Form als Mediumzusatz sowie als solide Tr{\"a}gerstruktur w{\"a}hrend der Differenzierung von hiPS zu hormonexprimierenden Zellen (Rezania et al. 2012; Rezania et al. 2014) oder maturierenden β-Zellen verwendet (Rezania et al. 2014). Der Effekt der PanMa wurde anhand von Genexpressions-analysen, immunhistochemischer F{\"a}rbungen und Analysen zur Glukose-abh{\"a}ngigen Insulinsekretion untersucht. In einem letzten Teil der Studie wurde die Eignung der PanMa zur verl{\"a}ngerten Kultivierung von hiPS-abgeleiteten endokrinen Zellen des Pankreas im Hinblick auf die Etablierung eines Organmodells des endokrinen Pankreas getestet. Hierzu wurde die PanMa zu einem Hydrogel weiterverarbeitet, welches zur Einkapselung und Kultivierung von hiPS-abgeleiteten hormonexprimierenden Zellen eingesetzt wurde. Um die Auswirkungen der Hydrogel-Kultur nachzuvollziehen, wurden die kultivierten Zellen mittels Genexpression, immun-histochemischer F{\"a}rbungen und Analysen zur Glukose-abh{\"a}ngigen Insulinsekretion untersucht. Mittels Dezellularisierung porziner Pankreaten konnte eine zellfreie, pankreasspezifische EZM-Tr{\"a}gerstruktur mit geringen Restbest{\"a}nden an DNA sowie einer weitgehend erhaltenen Mikro- und Ultrastruktur mit typischen EZM-Komponenten wie Kollagen I, III und IV hergestellt werden. Im Rahmen der Besiedelung arterieller Gef{\"a}ße mit humanen Endothelzellen wurde die Zellkompatibilit{\"a}t der hergestellten PanMa sowie eine weitgehende Unversehrtheit der Gef{\"a}ßstrukturen nachgewiesen. Verglichen zu SISser und LungMa zeichnete sich die PanMa als eine relativ weiche, stark wasserbindende, faserbasierte Struktur aus. Weiterhin konnten Hinweise f{\"u}r einen Effekt der PanMa auf den Stammzellcharakter und die fr{\"u}he Entwicklung von hiPS beobachtet werden. Hierbei f{\"u}hrte die Erhaltung von hiPS auf der PanMa zu einer leicht ver{\"a}nderten Expression von Genen des Kernpluripotenznetzwerks sowie zu einem reduziertem NANOG-Proteinsignal. Einhergehend mit diesen Beobachtungen zeigten hiPS w{\"a}hrend spontaner Differenzierung auf der PanMa eine verst{\"a}rkte endodermale Entwicklung. Im Verlauf der pankreatischen Differenzierung f{\"u}hrte die Kultivierung auf der PanMa zu einer signifikant verringerten Expression von Glukagon und Somatostatin, w{\"a}hrend die Expression von Insulin unver{\"a}ndert blieb, was auf eine Verminderung endokriner α- und δ-Zellen hinweist. Diese Ver{\"a}nderung {\"a}ußerte sich jedoch nicht in einer verbesserten Glukose-abh{\"a}ngigen Insulinsekretion der generierten hormonexprimierenden Zellen. Unter Anwendung der PanMa als Hydrogel konnten hormonexprimierenden Zellen {\"u}ber einen verl{\"a}ngerten Zeitraum kultiviert werden. Nach 21 Tagen in Kultur zeigten die eingekapselten hormonexprimierenden Zellen eine unver{\"a}ndert hohe Viabilit{\"a}t, wiesen allerdings bereits eine erste ver{\"a}nderte Zellanordnung sowie eine leicht verminderte Glukose-abh{\"a}ngige Insulinsekretion auf. Zusammengefasst konnte in dieser Studie ein biologischer Effekt gewebespezifischer EZM-Merkmale auf die Differenzierung von hiPS nachgewiesen werden. Dar{\"u}ber hinaus weisen die Daten auf eine relevante Funktion der EZM im Rahmen der endokrinen Spezifizierung von hiPS w{\"a}hrend der pankreatischen Differenzierung hin. Diese Beobachtungen verdeutlichen die eminente Rolle der EZM in der Herstellung von funktionalen hiPS-abgeleiteten Zellen und pl{\"a}dieren f{\"u}r eine st{\"a}rkere Einbindung organspezifischer EZMs im Bereich des Tissue Engineering und der klinischen Translation in der Regenerativen Medizin.},
  subject      = {Bauchspeicheldr{\"u}se},
  language  = {en}
}
@article{WagenbrennerPokerHeinzetal.2022,
  author    = {Wagenbrenner, Mike and Poker, Konrad and Heinz, Tizian and Herrmann, Marietta and Horas, Konstantin and Ebert, Regina and Mayer-Wagner, Susanne and Holzapfel, Boris M. and Rudert, Maximilian and Steinert, Andre F. and Weißenberger, Manuel},
  title     = {Mesenchymal stromal cells (MSCs) isolated from various tissues of the human arthritic knee joint possess similar multipotent differentiation potential},
  series = {Applied Sciences},
  volume    = {12},
  journal   = {Applied Sciences},
  number    = {4},
  issn      = {2076-3417},
  doi       = {10.3390/app12042239},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262334},
  year      = {2022},
  abstract  = {(1) Background: The mesenchymal stromal cells (MSCs) of different tissue origins are applied in cell-based chondrogenic regeneration. However, there is a lack of comparability determining the most suitable cell source for the tissue engineering (TE) of cartilage. The purpose of this study was to compare the in vitro chondrogenic potential of MSC-like cells from different tissue sources (bone marrow, meniscus, anterior cruciate ligament, synovial membrane, and the infrapatellar fat pad removed during total knee arthroplasty (TKA)) and define which cell source is best suited for cartilage regeneration. (2) Methods: MSC-like cells were isolated from five donors and expanded using adherent monolayer cultures. Differentiation was induced by culture media containing specific growth factors. Transforming growth factor (TGF)-ß1 was used as the growth factor for chondrogenic differentiation. Osteogenesis and adipogenesis were induced in monolayer cultures for 27 days, while pellet cell cultures were used for chondrogenesis for 21 days. Control cultures were maintained under the same conditions. After, the differentiation period samples were analyzed, using histological and immunohistochemical staining, as well as molecularbiological analysis by RT-PCR, to assess the expression of specific marker genes. (3) Results: Plastic-adherent growth and in vitro trilineage differentiation capacity of all isolated cells were proven. Flow cytometry revealed the clear co-expression of surface markers CD44, CD73, CD90, and CD105 on all isolated cells. Adipogenesis was validated through the formation of lipid droplets, while osteogenesis was proven by the formation of calcium deposits within differentiated cell cultures. The formation of proteoglycans was observed during chondrogenesis in pellet cultures, with immunohistochemical staining revealing an increased relative gene expression of collagen type II. RT-PCR proved an elevated expression of specific marker genes after successful differentiation, with no significant differences regarding different cell source of native tissue. (4) Conclusions: Irrespective of the cell source of native tissue, all MSC-like cells showed multipotent differentiation potential in vitro. The multipotent differentiation capacity did not differ significantly, and chondrogenic differentiation was proven in all pellet cultures. Therefore, cell suitability for cell-based cartilage therapies and tissue engineering is given for various tissue origins that are routinely removed during total knee arthroplasty (TKA). This study might provide essential information for the clinical tool of cell harvesting, leading to more flexibility in cell availability.},
  language  = {en}
}
@article{WagenbrennerMayerWagnerRudertetal.2021,
  author    = {Wagenbrenner, Mike and Mayer-Wagner, Susanne and Rudert, Maximilian and Holzapfel, Boris Michael and Weissenberger, Manuel},
  title     = {Combinations of hydrogels and mesenchymal stromal cells (MSCs) for cartilage tissue engineering — a review of the literature},
  series = {Gels},
  volume    = {7},
  journal   = {Gels},
  number    = {4},
  issn      = {2310-2861},
  doi       = {10.3390/gels7040217},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250177},
  year      = {2021},
  abstract  = {Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.},
  language  = {en}
}
@article{PereiraTrivanovićHerrmann2019,
  author    = {Pereira, A. R. and Trivanović, D. and Herrmann, M.},
  title     = {Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro},
  series = {European Cells and Materials},
  volume    = {37},
  journal   = {European Cells and Materials},
  issn      = {1473-2262},
  doi       = {10.22203/eCM.v037a07},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268823},
  pages     = {88-112},
  year      = {2019},
  abstract  = {Mesenchymal stem/stromal cells (MSCs) are an essential element of most modern tissue engineering and regenerative medicine approaches due to their multipotency and immunoregulatory functions. Despite the prospective value of MSCs for the clinics, the stem cells community is questioning their developmental origin, in vivo localization, identification, and regenerative potential after several years of far-reaching research in the field. Although several major progresses have been made in mimicking the complexity of the MSC niche in vitro, there is need for comprehensive studies of fundamental mechanisms triggered by microenvironmental cues before moving to regenerative medicine cell therapy applications. The present comprehensive review extensively discusses the microenvironmental cues that influence MSC phenotype and function in health and disease - including cellular, chemical and physical interactions. The most recent and relevant illustrative examples of novel bioengineering approaches to mimic biological, chemical, and mechanical microenvironmental signals present in the native MSC niche are summarized, with special emphasis on the forefront techniques to achieve bio-chemical complexity and dynamic cultures. In particular, the skeletal MSC niche and applications focusing on the bone regenerative potential of MSC are addressed. The aim of the review was to recognize the limitations of the current MSC niche in vitro models and to identify potential opportunities to fill the bridge between fundamental science and clinical application of MSCs.},
  language  = {en}
}
@article{HrynevichAchenbachJungstetal.2021,
  author    = {Hrynevich, Andrei and Achenbach, Pascal and Jungst, Tomasz and Brook, Gary A. and Dalton, Paul D.},
  title     = {Design of Suspended Melt Electrowritten Fiber Arrays for Schwann Cell Migration and Neurite Outgrowth},
  series = {Macromolecular Bioscience},
  volume    = {21},
  journal   = {Macromolecular Bioscience},
  number    = {7},
  doi       = {10.1002/mabi.202000439},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257535},
  year      = {2021},
  abstract  = {In this study, well-defined, 3D arrays of air-suspended melt electrowritten fibers are made from medical grade poly(ɛ-caprolactone) (PCL). Low processing temperatures, lower voltages, lower ambient temperature, increased collector distance, and high collector speeds all aid to direct-write suspended fibers that can span gaps of several millimeters between support structures. Such processing parameters are quantitatively determined using a "wedge-design" melt electrowritten test frame to identify the conditions that increase the suspension probability of long-distance fibers. All the measured parameters impact the probability that a fiber is suspended over multimillimeter distances. The height of the suspended fibers can be controlled by a concurrently fabricated fiber wall and the 3D suspended PCL fiber arrays investigated with early post-natal mouse dorsal root ganglion explants. The resulting Schwann cell and neurite outgrowth extends substantial distances by 21 d, following the orientation of the suspended fibers and the supporting walls, often generating circular whorls of high density Schwann cells between the suspended fibers. This research provides a design perspective and the fundamental parametric basis for suspending individual melt electrowritten fibers into a form that facilitates cell culture.},
  language  = {en}
}
@article{HaeusnerHerbstBittorfetal.2021,
  author    = {Haeusner, Sebastian and Herbst, Laura and Bittorf, Patrick and Schwarz, Thomas and Henze, Chris and Mauermann, Marc and Ochs, Jelena and Schmitt, Robert and Blache, Ulrich and Wixmerten, Anke and Miot, Sylvie and Martin, Ivan and Pullig, Oliver},
  title     = {From Single Batch to Mass Production-Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product},
  series = {Frontiers in Medicine},
  volume    = {8},
  journal   = {Frontiers in Medicine},
  issn      = {2296-858X},
  doi       = {10.3389/fmed.2021.712917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244631},
  year      = {2021},
  abstract  = {Advanced Therapy Medicinal Products (ATMP) provide promising treatment options particularly for unmet clinical needs, such as progressive and chronic diseases where currently no satisfying treatment exists. Especially from the ATMP subclass of Tissue Engineered Products (TEPs), only a few have yet been translated from an academic setting to clinic and beyond. A reason for low numbers of TEPs in current clinical trials and one main key hurdle for TEPs is the cost and labor-intensive manufacturing process. Manual production steps require experienced personnel, are challenging to standardize and to scale up. Automated manufacturing has the potential to overcome these challenges, toward an increasing cost-effectiveness. One major obstacle for automation is the control and risk prevention of cross contaminations, especially when handling parallel production lines of different patient material. These critical steps necessitate validated effective and efficient cleaning procedures in an automated system. In this perspective, possible technologies, concepts and solutions to existing ATMP manufacturing hurdles are discussed on the example of a late clinical phase II trial TEP. In compliance to Good Manufacturing Practice (GMP) guidelines, we propose a dual arm robot based isolator approach. Our novel concept enables complete process automation for adherent cell culture, and the translation of all manual process steps with standard laboratory equipment. Moreover, we discuss novel solutions for automated cleaning, without the need for human intervention. Consequently, our automation concept offers the unique chance to scale up production while becoming more cost-effective, which will ultimately increase TEP availability to a broader number of patients.},
  language  = {en}
}
@article{HindererShenRinguetteetal.2015,
  author    = {Hinderer, Svenja and Shen, Nian and Ringuette, L{\´e}a-Jeanne and Hansmann, Jan and Reinhardt, Dieter P and Brucker, Sara Y and Davis, Elaine C and Schenke-Layland, Katja},
  title     = {In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold},
  series = {Biomedical Materials},
  volume    = {10},
  journal   = {Biomedical Materials},
  number    = {3},
  doi       = {10.1088/1748-6041/10/3/034102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254074},
  year      = {2015},
  abstract  = {Elastic fibers are essential for the proper function of organs including cardiovascular tissues such as heart valves and blood vessels. Although (tropo)elastin production in a tissue-engineered construct has previously been described, the assembly to functional elastic fibers in vitro using human cells has been highly challenging. In the present study, we seeded primary isolated human vascular smooth muscle cells (VSMCs) onto 3D electrospun scaffolds and exposed them to defined laminar shear stress using a customized bioreactor system. Increased elastin expression followed by elastin deposition onto the electrospun scaffolds, as well as on newly formed fibers, was observed after six days. Most interestingly, we identified the successful deposition of elastogenesis-associated proteins, including fibrillin-1 and -2, fibulin-4 and -5, fibronectin, elastin microfibril interface located protein 1 (EMILIN-1) and lysyl oxidase (LOX) within our engineered constructs. Ultrastructural analyses revealed a developing extracellular matrix (ECM) similar to native human fetal tissue, which is composed of collagens, microfibrils and elastin. To conclude, the combination of a novel dynamic flow bioreactor and an electrospun hybrid polymer scaffold allowed the production and assembly of an elastic fiber-containing ECM.},
  language  = {en}
}
@article{SchmidtAbinzanoMensingaetal.2020,
  author    = {Schmidt, Stefanie and Abinzano, Florencia and Mensinga, Anneloes and Teßmar, J{\"o}rg and Groll, J{\"u}rgen and Malda, Jos and Levato, Riccardo and Blunk, Torsten},
  title     = {Differential production of cartilage ECM in 3D agarose constructs by equine articular cartilage progenitor cells and mesenchymal stromal cells},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {19},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21197071},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236180},
  year      = {2020},
  abstract  = {Identification of articular cartilage progenitor cells (ACPCs) has opened up new opportunities for cartilage repair. These cells may be used as alternatives for or in combination with mesenchymal stromal cells (MSCs) in cartilage engineering. However, their potential needs to be further investigated, since only a few studies have compared ACPCs and MSCs when cultured in hydrogels. Therefore, in this study, we compared chondrogenic differentiation of equine ACPCs and MSCs in agarose constructs as monocultures and as zonally layered co-cultures under both normoxic and hypoxic conditions. ACPCs and MSCs exhibited distinctly differential production of the cartilaginous extracellular matrix (ECM). For ACPC constructs, markedly higher glycosaminoglycan (GAG) contents were determined by histological and quantitative biochemical evaluation, both in normoxia and hypoxia. Differential GAG production was also reflected in layered co-culture constructs. For both cell types, similar staining for type II collagen was detected. However, distinctly weaker staining for undesired type I collagen was observed in the ACPC constructs. For ACPCs, only very low alkaline phosphatase (ALP) activity, a marker of terminal differentiation, was determined, in stark contrast to what was found for MSCs. This study underscores the potential of ACPCs as a promising cell source for cartilage engineering.},
  language  = {en}
}
@article{SulimanSunPedersenetal.2016,
  author    = {Suliman, Salwa and Sun, Yang and Pedersen, Torbjorn O. and Xue, Ying and Nickel, Joachim and Waag, Thilo and Finne-Wistrand, Anna and Steinm{\"u}ller-Nethl, Doris and Krueger, Anke and Costea, Daniela E. and Mustafa, Kamal},
  title     = {In vivo host response and degradation of copolymer scaffolds functionalized with nanodiamonds and bone morphogenetic protein 2},
  series = {Advanced Healthcare Materials},
  volume    = {5},
  journal   = {Advanced Healthcare Materials},
  number    = {6},
  doi       = {10.1002/adhm.201500723},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189764},
  pages     = {730-742},
  year      = {2016},
  abstract  = {The aim is to evaluate the effect of modifying poly[(L-lactide)-co-(epsilon-caprolactone)] scaffolds (PLCL) with nanodiamonds (nDP) or with nDP+physisorbed BMP-2 (nDP+BMP-2) on in vivo host tissue response and degradation. The scaffolds are implanted subcutaneously in Balb/c mice and retrieved after 1, 8, and 27 weeks. Molecular weight analysis shows that modified scaffolds degrade faster than the unmodified. Gene analysis at week 1 shows highest expression of proinflammatory markers around nDP scaffolds; although the presence of inflammatory cells and foreign body giant cells is more prominent around the PLCL. Tissue regeneration markers are highly expressed in the nDP+BMP-2 scaffolds at week 8. A fibrous capsule is detectable by week 8, thinnest around nDP scaffolds and at week 27 thickest around PLCL scaffolds. mRNA levels of ALP, COL1 alpha 2, and ANGPT1 are signifi cantly upregulating in the nDP+BMP-2 scaffolds at week 1 with ectopic bone seen at week 8. Even when almost 90\% of the scaffold is degraded at week 27, nDP are observable at implantation areas without adverse effects. In conclusion, modifying PLCL scaffolds with nDP does not aggravate the host response and physisorbed BMP-2 delivery attenuates infl ammation while lowering the dose of BMP-2 to a relatively safe and economical level.},
  language  = {en}
}
@article{SchmalzlPlumhoffGilbertetal.2019,
  author    = {Schmalzl, Jonas and Plumhoff, Piet and Gilbert, Fabian and Gohlke, Frank and Konrads, Christian and Brunner, Ulrich and Jakob, Franz and Ebert, Regina and Steinert, Andre F.},
  title     = {Tendon-derived stem cells from the long head of the biceps tendon},
  series = {Bone \& Joint Research},
  volume    = {8},
  journal   = {Bone \& Joint Research},
  number    = {9},
  doi       = {10.1302/2046-3758.89.BJR-2018-0214.R2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200370},
  pages     = {414-424},
  year      = {2019},
  abstract  = {Objectives The long head of the biceps (LHB) is often resected in shoulder surgery and could therefore serve as a cell source for tissue engineering approaches in the shoulder. However, whether it represents a suitable cell source for regenerative approaches, both in the inflamed and non-inflamed states, remains unclear. In the present study, inflamed and native human LHBs were comparatively characterized for features of regeneration. Methods In total, 22 resected LHB tendons were classified into inflamed samples (n = 11) and non-inflamed samples (n = 11). Proliferation potential and specific marker gene expression of primary LHB-derived cell cultures were analyzed. Multipotentiality, including osteogenic, adipogenic, chondrogenic, and tenogenic differentiation potential of both groups were compared under respective lineage-specific culture conditions. Results Inflammation does not seem to affect the proliferation rate of the isolated tendon-derived stem cells (TDSCs) and the tenogenic marker gene expression. Cells from both groups showed an equivalent osteogenic, adipogenic, chondrogenic and tenogenic differentiation potential in histology and real-time polymerase chain reaction (RT-PCR) analysis. Conclusion These results suggest that the LHB tendon might be a suitable cell source for regenerative approaches, both in inflamed and non-inflamed states. The LHB with and without tendinitis has been characterized as a novel source of TDSCs, which might facilitate treatment of degeneration and induction of regeneration in shoulder surgery.},
  language  = {en}
}
@article{GroeberEngelhardtLangeetal.2016,
  author    = {Groeber, Florian and Engelhardt, Lisa and Lange, Julia and Kurdyn, Szymon and Schmid, Freia F. and R{\"u}cker, Christoph and Mielke, Stephan and Walles, Heike and Hansmann, Jan},
  title     = {A First Vascularized Skin Equivalent as an Alternative to Animal Experimentation},
  series = {ALTEX - Alternatives to Animal Experimentation},
  volume    = {33},
  journal   = {ALTEX - Alternatives to Animal Experimentation},
  number    = {4},
  doi       = {10.14573/altex.1604041},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164438},
  pages     = {415-422},
  year      = {2016},
  abstract  = {Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin \& eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.},
  language  = {en}
}
@phdthesis{Kremer2019,
  author    = {Kremer, Antje},
  title     = {Tissue Engineering of a Vascularized Meniscus Implant},
  doi       = {10.25972/OPUS-18432},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184326},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The knee joint is a complex composite joint containing the C-shaped wedge-like menisci composed of fibrocartilage. Due to their complex composition and structure, they provide mechanical resilience to the knee joint protecting the articular cartilage. Because of the limited repair potential, meniscal injuries do not only affect the meniscus itself but also lead to altered joint homeostasis and inevitably to secondary osteoarthritis. The meniscus was characterized focusing on its anatomy, structure and meniscal markers such as aggrecan, collagen type I (Col I) and Col II. The components relevant for meniscus tissue engineering, namely cells, Col I scaffolds, biochemical and biomechanical stimuli were studied. Meniscal cells (MCs) were isolated from meniscus, mesenchymal stem cells (MSCs) from bone marrow and dermal microvascular endothelial cells (d-mvECs) from foreskin biopsies. For the human (h) meniscus model, wedge-shape compression of a hMSC-laden Col I gel was successfully established. During three weeks of static culture, the biochemical stimulus transforming growth factor beta-3 (TGF beta-3) led to a compact collagen structure. On day 21, this meniscus model showed high metabolic activity and matrix remodeling as confirmed by matrix metalloproteinases detection. The fibrochondrogenic properties were illustrated by immunohistochemical detection of meniscal markers, significant GAG/DNA increase and increased compressive properties. For further improvement, biomechanical stimulation systems by compression and hydrostatic pressure were designed. As one vascularization approach, direct stimulation with ciclopirox olamine (CPX) significantly increased sprouting of hd-mvEC spheroids even in absence of auxiliary cells such as MSCs. Second, a cell sheet composed of hMSCs and hd-mvECs was fabricated by temperature triggered cell sheet engineering and transferred onto the wedge-shaped meniscus model. Third, a biological vascularized scaffold (BioVaSc-TERM) was re-endothelialized with hd-mvECs providing a viable vascularized network. The vascularized BioVaSc-TERM was suggested as wrapping scaffold of the meniscus model by using two suture techniques, the all-inside-repair (AIR) for the posterior horn, and the outside-in-refixation (OIR) for the anterior horn and the middle part. This meniscus model for replacing torn menisci is a promising approach to be further optimized regarding vascularization, biochemical and biomechanical stimuli.},
  subject      = {Meniskus},
  language  = {en}
}
@article{LotzKiesewetterSchmidetal.2018,
  author    = {Lotz, C. and Kiesewetter, L. and Schmid, F. F. and Hansmann, J. and Walles, H. and Groeber-Becker, F.},
  title     = {Replacing the Draize eye test: impedance spectroscopy as a 3R method to discriminate between all GHS categories for eye irritation},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {15049},
  doi       = {10.1038/s41598-018-33118-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177492},
  year      = {2018},
  abstract  = {Highly invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns. However, besides all efforts, the Draize eye test is still not completely replaced by alternative animal-free methods. To develop an in vitro test to identify all categories of eye irritation, we combined organotypic cornea models based on primary human cells with an electrical readout system that measures the impedance of the test models. First, we showed that employing a primary human cornea epithelial cell based model is advantageous in native marker expression to the primary human epidermal keratinocytes derived models. Secondly, by employing a non-destructive measuring system based on impedance spectroscopy, we could increase the sensitivity of the test system. Thereby, all globally harmonized systems categories of eye irritation could be identified by repeated measurements over a period of 7 days. Based on a novel prediction model we achieved an accuracy of 78\% with a reproducibility of 88.9\% to determine all three categories of eye irritation in one single test. This could pave the way according to the 3R principle to replace the Draize eye test.},
  language  = {en}
}
@article{ThibaudeauTaubenbergerTheodoropoulosetal.2015,
  author    = {Thibaudeau, Laure and Taubenberger, Anna V. and Theodoropoulos, Christina and Holzapfel, Boris M. and Ramuz, Olivier and Straub, Melanie and Hutmacher, Dietmar W.},
  title     = {New mechanistic insights of integrin β1 in breast cancer bone colonization},
  series = {Oncotarget},
  volume    = {6},
  journal   = {Oncotarget},
  number    = {1},
  doi       = {10.18632/oncotarget.2788},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175432},
  pages     = {332-344},
  year      = {2015},
  abstract  = {Bone metastasis is a frequent and life-threatening complication of breast cancer. The molecular mechanisms supporting the establishment of breast cancer cells in the skeleton are still not fully understood, which may be attributed to the lack of suitable models that interrogate interactions between human breast cancer cells and the bone microenvironment. Although it is well-known that integrins mediate adhesion of malignant cells to bone extracellular matrix, their role during bone colonization remains unclear. Here, the role of β1 integrins in bone colonization was investigated using tissue-engineered humanized in vitro and in vivo bone models. In vitro, bone-metastatic breast cancer cells with suppressed integrin β1 expression showed reduced attachment, spreading, and migration within human bone matrix compared to control cells. Cell proliferation in vitro was not affected by β1 integrin knockdown, yet tumor growth in vivo within humanized bone microenvironments was significantly inhibited upon β1 integrin suppression, as revealed by quantitative in/ex vivo fluorescence imaging and histological analysis. Tumor cells invaded bone marrow spaces in the humanized bone and formed osteolytic lesions; osteoclastic bone resorption was, however, not reduced by β1 integrin knockdown. Taken together, we demonstrate that β1 integrins have a pivotal role in bone colonization using unique tissue-engineered humanized bone models.},
  language  = {en}
}
@phdthesis{Hochleitner2018,
  author    = {Hochleitner, Gernot},
  title     = {Advancing melt electrospinning writing for fabrication of biomimetic structures},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162197},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {In order to mimic the extracellular matrix for tissue engineering, recent research approaches often involve 3D printing or electrospinning of fibres to scaffolds as cell carrier material. Within this thesis, a micron fibre printing process, called melt electrospinning writing (MEW), combining both additive manufacturing and electrospinning, has been investigated and improved. Thus, a unique device was developed for accurate process control and manufacturing of high quality constructs. Thereby, different studies could be conducted in order to understand the electrohydrodynamic printing behaviour of different medically relevant thermoplastics as well as to characterise the influence of MEW on the resulting scaffold performance. For reproducible scaffold printing, a commonly occurring processing instability was investigated and defined as pulsing, or in extreme cases as long beading. Here, processing analysis could be performed with the aim to overcome those instabilities and prevent the resulting manufacturing issues. Two different biocompatible polymers were utilised for this study: poly(ε-caprolactone) (PCL) as the only material available for MEW until then and poly(2-ethyl-2-oxazoline) for the first time. A hypothesis including the dependency of pulsing regarding involved mass flows regulated by the feeding pressure and the electrical field strength could be presented. Further, a guide via fibre diameter quantification was established to assess and accomplish high quality printing of scaffolds for subsequent research tasks. By following a combined approach including small sized spinnerets, small flow rates and high field strengths, PCL fibres with submicron-sized fibre diameters (f{\O} = 817 ± 165 nm) were deposited to defined scaffolds. The resulting material characteristics could be investigated regarding molecular orientation and morphological aspects. Thereby, an alignment and isotropic crystallinity was observed that can be attributed to the distinct acceleration of the solidifying jet in the electrical field and by the collector uptake. Resulting submicron fibres formed accurate but mechanically sensitive structures requiring further preparation for a suitable use in cell biology. To overcome this handling issue, a coating procedure, by using hydrophilic and cross-linkable star-shaped molecules for preparing fibre adhesive but cell repellent collector surfaces, was used. Printing PCL fibre patterns below the critical translation speed (CTS) revealed the opportunity to manufacture sinusoidal shaped fibres analogously to those observed using purely viscous fluids falling on a moving belt. No significant influence of the high voltage field during MEW processing could be observed on the buckling phenomenon. A study on the sinusoidal geometry revealed increasing peak-to-peak values and decreasing wavelengths as a function of decreasing collector speeds sc between CTS > sc ≥ 2/3 CTS independent of feeding pressures. Resulting scaffolds printed at 100 \%, 90 \%, 80 \% and 70 \% of CTS exhibited significantly different tensile properties, foremost regarding Young's moduli (E = 42 ± 7 MPa to 173 ± 22 MPa at 1 - 3 \% strain). As known from literature, a changed morphology and mechanical environment can impact cell performance substantially leading to a new opportunity of tailoring TE scaffolds. Further, poly(L-lactide-co-ε-caprolactone-co-acryloyl carbonate) as well as poly(ε-caprolactone-co-acryloyl carbonate) (PCLAC) copolymers could be used for MEW printing. Those exhibit the opportunity for UV-initiated radical cross-linking in a post-processing step leading to significantly increased mechanical characteristics. Here, single fibres of the polymer composed of 90 mol.\% CL and 10 mol.\% AC showed a considerable maximum tensile strength of σmax = 53 ± 16 MPa. Furthermore, sinusoidal meanders made of PCLAC yielded a specific tensile stress-strain characteristic mimicking the qualitative behaviour of tendons or ligaments. Cell viability by L929 murine fibroblasts and live/dead staining with human mesenchymal stem cells revealed a promising biomaterial behaviour pointing out MEW printed PCLAC scaffolds as promising choice for medical repair of load-bearing soft tissue. Indeed, one apparent drawback, the small throughput similar to other AM methods, may still prevent MEW's industrial application yet. However, ongoing research focusses on enlargement of manufacturing speed with the clear perspective of relevant improvement. Thereby, the utilisation of large spinneret sizes may enable printing of high volume rates, while downsizing the resulting fibre diameter via electrical field and mechanical stretching by the collector uptake. Using this approach, limitations of FDM by small nozzle sizes could be overcome. Thinking visionary, such printing devices could be placed in hospitals for patient-specific printing-on-demand therapies one day. Taking the evolved high deposition precision combined with the unique small fibre diameter sizes into account, technical processing of high performance membranes, filters or functional surface finishes also stands to reason.},
  subject      = {scaffold},
  language  = {en}
}
@article{MollReboredoSchwarzetal.2013,
  author    = {Moll, Corinna and Reboredo, Jenny and Schwarz, Thomas and Appelt, Antje and Sch{\"u}rlein, Sebastian and Walles, Heike and Nietzer, Sarah},
  title     = {Tissue Engineering of a Human 3D in vitro Tumor Test System},
  series = {Journal of Visualized Experiments},
  volume    = {78},
  journal   = {Journal of Visualized Experiments},
  number    = {e50460},
  doi       = {10.3791/50460},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132277},
  year      = {2013},
  abstract  = {Cancer is one of the leading causes of death worldwide. Current therapeutic strategies are predominantly developed in 2D culture systems, which inadequately reflect physiological conditions in vivo. Biological 3D matrices provide cells an environment in which cells can self-organize, allowing the study of tissue organization and cell differentiation. Such scaffolds can be seeded with a mixture of different cell types to study direct 3D cell-cell-interactions. To mimic the 3D complexity of cancer tumors, our group has developed a 3D in vitro tumor test system. Our 3D tissue test system models the in vivo situation of malignant peripheral nerve sheath tumors (MPNSTs), which we established with our decellularized porcine jejunal segment derived biological vascularized scaffold (BioVaSc). In our model, we reseeded a modified BioVaSc matrix with primary fibroblasts, microvascular endothelial cells (mvECs) and the S462 tumor cell line For static culture, the vascular structure of the BioVaSc is removed and the remaining scaffold is cut open on one side (Small Intestinal Submucosa SIS-Muc). The resulting matrix is then fixed between two metal rings (cell crowns). Another option is to culture the cell-seeded SIS-Muc in a flow bioreactor system that exposes the cells to shear stress. Here, the bioreactor is connected to a peristaltic pump in a self-constructed incubator. A computer regulates the arterial oxygen and nutrient supply via parameters such as blood pressure, temperature, and flow rate. This setup allows for a dynamic culture with either pressure-regulated pulsatile or constant flow. In this study, we could successfully establish both a static and dynamic 3D culture system for MPNSTs. The ability to model cancer tumors in a more natural 3D environment will enable the discovery, testing, and validation of future pharmaceuticals in a human-like model.},
  language  = {en}
}