@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}
}
@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}
}