@phdthesis{Kress2019,
  author    = {Kreß, Sebastian},
  title     = {Development and proof of concept of a biological vascularized cell-based drug delivery system},
  doi       = {10.25972/OPUS-17865},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178650},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {A major therapeutic challenge is the increasing incidence of chronic disorders. The persistent impairment or loss of tissue function requires constitutive on-demand drug availability optimally achieved by a drug delivery system ideally directly connected to the blood circulation of the patient. However, despite the efforts and achievements in cell-based therapies and the generation of complex and customized cell-specific microenvironments, the generation of functional tissue is still unaccomplished. This study demonstrates the capability to generate a vascularized platform technology to potentially overcome the supply restraints for graft development and clinical application with immediate anastomosis to the blood circulation. The ability to decellularize segments of the rat intestine while preserving the ECM for subsequent reendothelialization was proven. The reestablishment of a functional arteriovenous perfusion circuit enabled the supply of co-cultured cells capable to replace the function of damaged tissue or to serve as a drug delivery system. During in vitro studies, the applicability of the developed miniaturized biological vascularized scaffold (mBioVaSc-TERM®) was demonstrated. While indicating promising results in short term in vivo studies, long term implantations revealed current limitations for the translation into clinical application. The gained insights will impact further improvements of quality and performance of this promising platform technology for future regenerative therapies.},
  subject      = {Vaskularisation},
  language  = {en}
}
@article{BingShiTanKressCastroetal.2013,
  author    = {Bing-Shi Tan, Ariel and Kress, Sebastian and Castro, Leticia and Sheppard, Allan and Raghunath, Michael},
  title     = {Cellular re- and de-programming by microenvironmental memory: why short TGF-β1 pulses can have long effects},
  series = {Fibrogenesis Tissue Repair},
  volume    = {6},
  journal   = {Fibrogenesis Tissue Repair},
  number    = {12},
  doi       = {10.1186/1755-1536-6-12},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131898},
  year      = {2013},
  abstract  = {Background Fibrosis poses a substantial setback in regenerative medicine. Histopathologically, fibrosis is an excessive accumulation of collagen affected by myofibroblasts and this can occur in any tissue that is exposed to chronic injury or insult. Transforming growth factor (TGF)-β1, a crucial mediator of fibrosis, drives differentiation of fibroblasts into myofibroblasts. These cells exhibit α-smooth muscle actin (α-SMA) and synthesize high amounts of collagen I, the major extracellular matrix (ECM) component of fibrosis. While hormones stimulate cells in a pulsatile manner, little is known about cellular response kinetics upon growth factor impact. We therefore studied the effects of short TGF-β1 pulses in terms of the induction and maintenance of the myofibroblast phenotype. Results Twenty-four hours after a single 30 min TGF-β1 pulse, transcription of fibrogenic genes was upregulated, but subsided 7 days later. In parallel, collagen I secretion rate and α-SMA presence were elevated for 7 days. A second pulse 24 h later extended the duration of effects to 14 days. We could not establish epigenetic changes on fibrogenic target genes to explain the long-lasting effects. However, ECM deposited under singly pulsed TGF-β1 was able to induce myofibroblast features in previously untreated fibroblasts. Dependent on the age of the ECM (1 day versus 7 days' formation time), this property was diminished. Vice versa, myofibroblasts were cultured on fibroblast ECM and cells observed to express reduced (in comparison with myofibroblasts) levels of collagen I. Conclusions We demonstrated that short TGF-β1 pulses can exert long-lasting effects on fibroblasts by changing their microenvironment, thus leaving an imprint and creating a reciprocal feed-back loop. Therefore, the ECM might act as mid-term memory for pathobiochemical events. We would expect this microenvironmental memory to be dependent on matrix turnover and, as such, to be erasable. Our findings contribute to the current understanding of fibroblast induction and maintenance, and have bearing on the development of antifibrotic drugs.},
  language  = {en}
}
@article{KressBaurOttoetal.2018,
  author    = {Kress, Sebastian and Baur, Johannes and Otto, Christoph and Burkard, Natalie and Braspenning, Joris and Walles, Heike and Nickel, Joachim and Metzger, Marco},
  title     = {Evaluation of a miniaturized biologically vascularized scaffold in vitro and in vivo},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {4719},
  doi       = {10.1038/s41598-018-22688-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176343},
  year      = {2018},
  abstract  = {In tissue engineering, the generation and functional maintenance of dense voluminous tissues is mainly restricted due to insufficient nutrient supply. Larger three-dimensional constructs, which exceed the nutrient diffusion limit become necrotic and/or apoptotic in long-term culture if not provided with an appropriate vascularization. Here, we established protocols for the generation of a pre-vascularized biological scaffold with intact arterio-venous capillary loops from rat intestine, which is decellularized under preservation of the feeding and draining vascular tree. Vessel integrity was proven by marker expression, media/blood reflow and endothelial LDL uptake. In vitro maintenance persisted up to 7 weeks in a bioreactor system allowing a stepwise reconstruction of fully vascularized human tissues and successful in vivo implantation for up to 4 weeks, although with time-dependent decrease of cell viability. The vascularization of the construct lead to a 1.5× increase in cellular drug release compared to a conventional static culture in vitro. For the first time, we performed proof-of-concept studies demonstrating that 3D tissues can be maintained within a miniaturized vascularized scaffold in vitro and successfully implanted after re-anastomosis to the intrinsic blood circulation in vivo. We hypothesize that this technology could serve as a powerful platform technology in tissue engineering and regenerative medicine.},
  language  = {en}
}
@phdthesis{Kress2020,
  author    = {Kreß, Sebastian},
  title     = {Retrospektive Datenanalyse zum postoperativen Befinden von minimal-invasiv chirurgisch behandelten Patienten nach intraoperativer Gabe von Fentanyl oder Sufentanil},
  doi       = {10.25972/OPUS-21381},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213818},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Zusammenfassung: Fentanyl und Sufentanil sind zwei synthetisch hergestellte Opioide, die in der An{\"a}sthesiologie f{\"u}r die intraoperative Analgesie eingesetzt werden. Sie weisen ein unterschiedliches pharmakodynamisches Profil auf. Im Jahr 2014 wurde das Opioidregime f{\"u}r minimal-invasive Standardeingriffe im Klinikum Fulda von Fentanyl auf Sufentanil umgestellt. In der geplanten retrospektiven Datenerhebung sollten Daten von Patienten, die vor 2014 mit Fentanyl analgesiert wurden, verglichen werden mit Daten von Patienten, bei denen nach 2014 Sufentanil in die Narkosef{\"u}hrung implementiert war. Untersucht werden sollte, ob der Wechsel auf ein Opioid mit einem vermeintlich geeigneteren Profil f{\"u}r die Narkosef{\"u}hrung tats{\"a}chlich die kalkulierten Vorteile erbracht hat. Die retrospektive Datenerhebung sollte aufzeigen, ob Patienten w{\"a}hrend und nach MIC-CHE oder MIC-TEP von einer Sufentanil-Gabe gegen{\"u}ber der Fentanyl-Gabe profitieren: Verk{\"u}rzt sich die Ausleitungsphase, haben die Patienten bei Ankunft im Aufwachraum (AWR) eine bessere Oxygenierung und/oder eine stabilere Kreislaufsituation? Leiden die Patienten nach Sufentanil unter weniger postoperativer {\"U}belkeit und Erbrechen (PONV), ben{\"o}tigen sie weniger Schmerzmittel? Die Untersuchung sollte zudem kl{\"a}ren, ob biometrische Faktoren wie Geschlecht, Alter, Gewicht und BMI in Zusammenhang mit dem eingesetzten Opioid eine relevante Rolle f{\"u}r das postoperative Befinden der Patienten spielten, und ob sich aus der Umstellung von Fentanyl auf Sufentanil {\"o}konomische Vorteile ergaben. Ergebnis: Kombination Desfluran mit Sufentanil f{\"u}r alle untersuchten Gruppen von klinischem Vorteil. Bevorzugter Einsatz bei MIC-Eingriffen in der Allgemein- und Viszeralchirurgie empfehlenswert. - Geringerer postoperativer Schmerzmittelbedarf - Bessere postoperative Oxygenierung - K{\"u}rzere postoperative Aufwachzeit - Niedrigerer intraoperativer Opioidbedarf - Wirtschaftlich/{\"o}konomische Gleichwert Begr{\"u}ndete Aussage, dass Sufentanil bei MIC-Eingriffen in der Allgemein- und Viszeralchirurgie im Vergleich zu Fentanyl das {\"u}berlegene Medikament ist. ({\"u}berwiegend statistisch signifikant) Steigerung dieses Effekts {\"u}ber die Kombination mit Desfluran m{\"o}glich.},
  subject      = {Fentanyl},
  language  = {de}
}