@article{BousquetAntoBachertetal.2021,
  author    = {Bousquet, Jean and Anto, Josep M. and Bachert, Claus and Haahtela, Tari and Zuberbier, Torsten and Czarlewski, Wienczyslawa and Bedbrook, Anna and Bosnic-Anticevich, Sinthia and Walter Canonica, G. and Cardona, Victoria and Costa, Elisio and Cruz, Alvaro A. and Erhola, Marina and Fokkens, Wytske J. and Fonseca, Joao A. and Illario, Maddalena and Ivancevich, Juan-Carlos and Jutel, Marek and Klimek, Ludger and Kuna, Piotr and Kvedariene, Violeta and Le, LTT and Larenas-Linnemann, D{\´e}sir{\´e}e E. and Laune, Daniel and Louren{\c{c}}o, Olga M. and Mel{\´e}n, Erik and Mullol, Joaquim and Niedoszytko, Marek and Odemyr, Mika{\"e}la and Okamoto, Yoshitaka and Papadopoulos, Nikos G. and Patella, Vincenzo and Pfaar, Oliver and Pham-Thi, Nh{\^a}n and Rolland, Christine and Samolinski, Boleslaw and Sheikh, Aziz and Sofiev, Mikhail and Suppli Ulrik, Charlotte and Todo-Bom, Ana and Tomazic, Peter-Valentin and Toppila-Salmi, Sanna and Tsiligianni, Ioanna and Valiulis, Arunas and Valovirta, Erkka and Ventura, Maria-Teresa and Walker, Samantha and Williams, Sian and Yorgancioglu, Arzu and Agache, Ioana and Akdis, Cezmi A. and Almeida, Rute and Ansotegui, Ignacio J. and Annesi-Maesano, Isabella and Arnavielhe, Sylvie and Basaga{\~n}a, Xavier and D. Bateman, Eric and B{\´e}dard, Annabelle and Bedolla-Barajas, Martin and Becker, Sven and Bennoor, Kazi S. and Benveniste, Samuel and Bergmann, Karl C. and Bewick, Michael and Bialek, Slawomir and E. Billo, Nils and Bindslev-Jensen, Carsten and Bjermer, Leif and Blain, Hubert and Bonini, Matteo and Bonniaud, Philippe and Bosse, Isabelle and Bouchard, Jacques and Boulet, Louis-Philippe and Bourret, Rodolphe and Boussery, Koen and Braido, Fluvio and Briedis, Vitalis and Briggs, Andrew and Brightling, Christopher E. and Brozek, Jan and Brusselle, Guy and Brussino, Luisa and Buhl, Roland and Buonaiuto, Roland and Calderon, Moises A. and Camargos, Paulo and Camuzat, Thierry and Caraballo, Luis and Carriazo, Ana-Maria and Carr, Warner and Cartier, Christine and Casale, Thomas and Cecchi, Lorenzo and Cepeda Sarabia, Alfonso M. and H. Chavannes, Niels and Chkhartishvili, Ekaterine and Chu, Derek K. and Cingi, Cemal and Correia de Sousa, Jaime and Costa, David J. and Courbis, Anne-Lise and Custovic, Adnan and Cvetkosvki, Biljana and D'Amato, Gennaro and da Silva, Jane and Dantas, Carina and Dokic, Dejan and Dauvilliers, Yves and De Feo, Giulia and De Vries, Govert and Devillier, Philippe and Di Capua, Stefania and Dray, Gerard and Dubakiene, Ruta and Durham, Stephen R. and Dykewicz, Mark and Ebisawa, Motohiro and Gaga, Mina and El-Gamal, Yehia and Heffler, Enrico and Emuzyte, Regina and Farrell, John and Fauquert, Jean-Luc and Fiocchi, Alessandro and Fink-Wagner, Antje and Fontaine, Jean-Fran{\c{c}}ois and Fuentes Perez, Jos{\´e} M. and Gemicioğlu, Bilun and Gamkrelidze, Amiran and Garcia-Aymerich, Judith and Gevaert, Philippe and Gomez, Ren{\´e} Maximiliano and Gonz{\´a}lez Diaz, Sandra and Gotua, Maia and Guldemond, Nick A. and Guzm{\´a}n, Maria-Antonieta and Hajjam, Jawad and Huerta Villalobos, Yunuen R. and Humbert, Marc and Iaccarino, Guido and Ierodiakonou, Despo and Iinuma, Tomohisa and Jassem, Ewa and Joos, Guy and Jung, Ki-Suck and Kaidashev, Igor and Kalayci, Omer and Kardas, Przemyslaw and Keil, Thomas and Khaitov, Musa and Khaltaev, Nikolai and Kleine-Tebbe, Jorg and Kouznetsov, Rostislav and Kowalski, Marek L. and Kritikos, Vicky and Kull, Inger and La Grutta, Stefania and Leonardini, Lisa and Ljungberg, Henrik and Lieberman, Philip and Lipworth, Brian and Lodrup Carlsen, Karin C. and Lopes-Pereira, Catarina and Loureiro, Claudia C. and Louis, Renaud and Mair, Alpana and Mahboub, Bassam and Makris, Micha{\"e}l and Malva, Joao and Manning, Patrick and Marshall, Gailen D. and Masjedi, Mohamed R. and Maspero, Jorge F. and Carreiro-Martins, Pedro and Makela, Mika and Mathieu-Dupas, Eve and Maurer, Marcus and De Manuel Keenoy, Esteban and Melo-Gomes, Elisabete and Meltzer, Eli O. and Menditto, Enrica and Mercier, Jacques and Micheli, Yann and Miculinic, Neven and Mihaltan, Florin and Milenkovic, Branislava and Mitsias, Dimitirios I. and Moda, Giuliana and Mogica-Martinez, Maria-Dolores and Mohammad, Yousser and Montefort, Steve and Monti, Ricardo and Morais-Almeida, Mario and M{\"o}sges, Ralph and M{\"u}nter, Lars and Muraro, Antonella and Murray, Ruth and Naclerio, Robert and Napoli, Luigi and Namazova-Baranova, Leyla and Neffen, Hugo and Nekam, Kristoff and Neou, Angelo and Nordlund, Bj{\"o}rn and Novellino, Ettore and Nyembue, Dieudonn{\´e} and O'Hehir, Robyn and Ohta, Ken and Okubo, Kimi and Onorato, Gabrielle L. and Orlando, Valentina and Ouedraogo, Solange and Palamarchuk, Julia and Pali-Sch{\"o}ll, Isabella and Panzner, Peter and Park, Hae-Sim and Passalacqua, Gianni and P{\´e}pin, Jean-Louis and Paulino, Ema and Pawankar, Ruby and Phillips, Jim and Picard, Robert and Pinnock, Hilary and Plavec, Davor and Popov, Todor A. and Portejoie, Fabienne and Price, David and Prokopakis, Emmanuel P. and Psarros, Fotis and Pugin, Benoit and Puggioni, Francesca and Quinones-Delgado, Pablo and Raciborski, Filip and Rajabian-S{\"o}derlund, Rojin and Regateiro, Frederico S. and Reitsma, Sietze and Rivero-Yeverino, Daniela and Roberts, Graham and Roche, Nicolas and Rodriguez-Zagal, Erendira and Rolland, Christine and Roller-Wirnsberger, Regina E. and Rosario, Nelson and Romano, Antonino and Rottem, Menachem and Ryan, Dermot and Salim{\"a}ki, Johanna and Sanchez-Borges, Mario M. and Sastre, Joaquin and Scadding, Glenis K. and Scheire, Sophie and Schmid-Grendelmeier, Peter and Sch{\"u}nemann, Holger J. and Sarquis Serpa, Faradiba and Shamji, Mohamed and Sisul, Juan-Carlos and Sofiev, Mikhail and Sol{\´e}, Dirceu and Somekh, David and Sooronbaev, Talant and Sova, Milan and Spertini, Fran{\c{c}}ois and Spranger, Otto and Stellato, Cristiana and Stelmach, Rafael and Thibaudon, Michel and To, Teresa and Toumi, Mondher and Usmani, Omar and Valero, Antonio A. and Valenta, Rudolph and Valentin-Rostan, Marylin and Pereira, Marilyn Urrutia and van der Kleij, Rianne and Van Eerd, Michiel and Vandenplas, Olivier and Vasankari, Tuula and Vaz Carneiro, Antonio and Vezzani, Giorgio and Viart, Fr{\´e}d{\´e}ric and Viegi, Giovanni and Wallace, Dana and Wagenmann, Martin and Wang, De Yun and Waserman, Susan and Wickman, Magnus and Williams, Dennis M. and Wong, Gary and Wroczynski, Piotr and Yiallouros, Panayiotis K. and Yusuf, Osman M. and Zar, Heather J. and Zeng, St{\´e}phane and Zernotti, Mario E. and Zhang, Luo and Shan Zhong, Nan and Zidarn, Mihaela},
  title     = {ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice},
  series = {Allergy},
  volume    = {76},
  journal   = {Allergy},
  number    = {1},
  doi       = {10.1111/all.14422},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228339},
  pages     = {168 -- 190},
  year      = {2021},
  abstract  = {Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.},
  language  = {en}
}
@article{SiverinoFahmyGarciaMumcuogluetal.2022,
  author    = {Siverino, Claudia and Fahmy-Garcia, Shorouk and Mumcuoglu, Didem and Oberwinkler, Heike and Muehlemann, Markus and Mueller, Thomas and Farrell, Eric and van Osch, Gerjo J. V. M. and Nickel, Joachim},
  title     = {Site-directed immobilization of an engineered bone morphogenetic protein 2 (BMP2) variant to collagen-based microspheres induces bone formation in vivo},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {7},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23073928},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284572},
  year      = {2022},
  abstract  = {For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.},
  language  = {en}
}
@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{SiverinoFahmyGarciaNiklausetal.2023,
  author    = {Siverino, Claudia and Fahmy-Garcia, Shorouk and Niklaus, Viktoria and Kops, Nicole and Dolcini, Laura and Misciagna, Massimiliano Maraglino and Ridwan, Yanto and Farrell, Eric and van Osch, Gerjo J. V. M. and Nickel, Joachim},
  title     = {Addition of heparin binding sites strongly increases the bone forming capabilities of BMP9 in vivo},
  series = {Bioactive Materials},
  volume    = {29},
  journal   = {Bioactive Materials},
  doi       = {10.1016/j.bioactmat.2023.07.010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350470},
  pages     = {241-250},
  year      = {2023},
  abstract  = {Highlights • Despite not being crucial for bone development BMP9 can induce bone growth in vivo. • BMP9 induced bone formation is strongly enhanced by introduced heparin binding sites. • BMP9s bone forming capabilities are triggered by extracellular matrix binding. • Heparin binding BMP9 (BMP9 HB) can improve the current therapies in treating bone fractures. Abstract Bone Morphogenetic proteins (BMPs) like BMP2 and BMP7 have shown great potential in the treatment of severe bone defects. In recent in vitro studies, BMP9 revealed the highest osteogenic potential compared to other BMPs, possibly due to its unique signaling pathways that differs from other osteogenic BMPs. However, in vivo the bone forming capacity of BMP9-adsorbed scaffolds is not superior to BMP2 or BMP7. In silico analysis of the BMP9 protein sequence revealed that BMP9, in contrast to other osteogenic BMPs such as BMP2, completely lacks so-called heparin binding motifs that enable extracellular matrix (ECM) interactions which in general might be essential for the BMPs' osteogenic function. Therefore, we genetically engineered a new BMP9 variant by adding BMP2-derived heparin binding motifs to the N-terminal segment of BMP9′s mature part. The resulting protein (BMP9 HB) showed higher heparin binding affinity than BMP2, similar osteogenic activity in vitro and comparable binding affinities to BMPR-II and ALK1 compared to BMP9. However, remarkable differences were observed when BMP9 HB was adsorbed to collagen scaffolds and implanted subcutaneously in the dorsum of rats, showing a consistent and significant increase in bone volume and density compared to BMP2 and BMP9. Even at 10-fold lower BMP9 HB doses bone tissue formation was observed. This innovative approach of significantly enhancing the osteogenic properties of BMP9 simply by addition of ECM binding motifs, could constitute a valuable replacement to the commonly used BMPs. The possibility to use lower protein doses demonstrates BMP9 HB's high translational potential.},
  language  = {en}
}