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Article: A perioperative layered autologous tissue expansion graft for hollow organ repair.

Willacy, Oliver / Juul, Nikolai / Taouzlak, Loai / Chamorro, Clara I / Ajallouiean, Fatemeh / Fossum, Magdalena

2024 Volume 10, Issue 3, Page(s) e25275

Abstract: Tissue engineering has not been widely adopted in clinical settings for several reasons, including technical challenges, high costs, and regulatory complexity. Here, we introduce the Perioperative Layered Autologous Tissue Expansion graft (PLATE graft), ... ...

Abstract	Tissue engineering has not been widely adopted in clinical settings for several reasons, including technical challenges, high costs, and regulatory complexity. Here, we introduce the Perioperative Layered Autologous Tissue Expansion graft (PLATE graft), a composite biomaterial and collagen-reinforced construct with autologous epithelium on one side and smooth muscle tissue on the other. Designed to mimic the structure and function of natural hollow organs, the PLATE graft is unique in that it can be produced in a standard operating theatre and is cost-effective. In this proof-of-principle study, we test its regenerative performance in eight different organs, present biomechanical and permeability tests, and finally explore its
Language	English
Publishing date	2024-01-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e25275
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Advancing autologous urothelial micrografting and composite tubular grafts for future single-staged urogenital reconstructions.

Juul, Nikolai / Ajalloueian, Fatemeh / Willacy, Oliver / Chamorro, Clara Ibel / Fossum, Magdalena

Scientific reports

2023 Volume 13, Issue 1, Page(s) 15584

Abstract: Urogenital reconstructive surgery can be impeded by lack of tissue. Further developments within the discipline of tissue engineering may be part of a solution to improve clinical outcomes. In this study, we aimed to design an accessible and easily ... ...

Abstract	Urogenital reconstructive surgery can be impeded by lack of tissue. Further developments within the discipline of tissue engineering may be part of a solution to improve clinical outcomes. In this study, we aimed to design an accessible and easily assembled tubular graft with autologous tissue, which could be constructed and implanted as a single-staged surgical procedure within the premises of an ordinary operating room. The ultimate goals would be to optimize current treatment-options for long-term urinary diversion. Therefore, we evaluated the optimal composition of a collagen-based scaffold with urothelial micrografts in vitro, and followingly implanted the construct in vivo as a bladder conduit. The scaffold was evaluated in relation to cell regeneration, permeability, and biomechanical properties. After establishing an optimized scaffold in vitro, consisting of high-density collagen with submerged autologous micrografts and reinforced with a mesh and stent, the construct was successfully implanted in an in vivo minipig model. The construct assemblance and surgical implantation proved feasible within the timeframe of a routine surgical intervention, and the animal quickly recovered postoperatively. Three weeks post-implantation, the conduit demonstrated good host-integration with a multilayered luminal urothelium. Our findings have encouraged us to support its use in more extensive preclinical large-animal studies.
MeSH term(s)	Animals ; Swine ; Urothelium ; Swine, Miniature ; Plastic Surgery Procedures ; Urogenital System ; Embryo Implantation
Language	English
Publishing date	2023-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-42092-3
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Article ; Online: What the Editors are reading - Basic science.

Wu, Hsi-Yang / Willacy, Oliver / Fossum, Magdalena

Journal of pediatric urology

2020 Volume 17, Issue 2, Page(s) 271–272

MeSH term(s)	Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Metabolome ; Publishing ; Reading
Language	English
Publishing date	2020-12-10
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	2237683-5
ISSN	1873-4898 ; 1477-5131
ISSN (online)	1873-4898
ISSN	1477-5131
DOI	10.1016/j.jpurol.2020.12.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Robot-Assisted vs. Open Appendicovesicostomy in Pediatric Urology: A Systematic Review and Single-Center Case Series.

Juul, Nikolai / Persad, Emma / Willacy, Oliver / Thorup, Jorgen / Fossum, Magdalena / Reinhardt, Susanne

Frontiers in pediatrics

2022 Volume 10, Page(s) 908554

Abstract: Introduction: Appendicovesicostomy (APV) is the preferred choice of continent catheterizable channels in pediatric urology. The introduction of robot-assisted laparoscopic techniques has been correlated to superior cosmesis and convalescence and is now ... ...

Abstract	Introduction: Appendicovesicostomy (APV) is the preferred choice of continent catheterizable channels in pediatric urology. The introduction of robot-assisted laparoscopic techniques has been correlated to superior cosmesis and convalescence and is now increasingly implemented for APV procedures. We aimed to perform a systematic review of the literature comparing open vs. robotic APV regarding possible differences in postoperative outcomes and to evaluate these findings with our own initial experiences with robotic APV compared to our previous open procedures. Methods: We evaluated the first five patients undergoing robotic APV at our institution and compared 1-year outcomes with a consecutive series of 12 patients undergoing open APV. In a systematic literature review, we screened studies from PubMed, EMBASE, and CENTRAL comparing open and robotic APV in pediatric urology (current to December 2021) and performed meta-analyses on postoperative outcomes comparing the two groups and evaluated the grade of evidence. Results: We found significantly shortened postoperative length of stay in the robotic group ( Conclusion: Robotic APV is equally safe to the conventional open approach with additional advantages in postoperative hospitalization length.
Language	English
Publishing date	2022-05-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2022.908554
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Article ; Online: Insights into cellular behavior and micromolecular communication in urothelial micrografts.

Juul, Nikolai / Willacy, Oliver / Mamand, Doste R / Andaloussi, Samir El / Eisfeldt, Jesper / Chamorro, Clara I / Fossum, Magdalena

Scientific reports

2023 Volume 13, Issue 1, Page(s) 13589

Abstract: Autologous micrografting is a technique currently applied within skin wound healing, however, the potential use for surgical correction of other organs with epithelial lining, including the urinary bladder, remains largely unexplored. Currently, little ... ...

Abstract	Autologous micrografting is a technique currently applied within skin wound healing, however, the potential use for surgical correction of other organs with epithelial lining, including the urinary bladder, remains largely unexplored. Currently, little is known about the micrograft expansion potential and the micromolecular events that occur in micrografted urothelial cells. In this study, we aimed to evaluate the proliferative potential of different porcine urothelial micrograft sizes in vitro, and, furthermore, to explore how urothelial micrografts communicate and which microcellular events are triggered. We demonstrated that increased tissue fragmentation subsequently potentiated the yield of proliferative cells and the cellular expansion potential, which confirms, that the micrografting principles of skin epithelium also apply to uroepithelium. Furthermore, we targeted the expression of the extracellular signal-regulated kinase (ERK) pathway and demonstrated that ERK activation occurred predominately at the micrograft borders and that ERK inhibition led to decreased urothelial migration and proliferation. Finally, we successfully isolated extracellular vesicles from the micrograft culture medium and evaluated their contents and relevance within various enriched biological processes. Our findings substantiate the potential of applying urothelial micrografting in future tissue-engineering models for reconstructive urological surgery, and, furthermore, highlights certain mechanisms as potential targets for future wound healing treatments.
MeSH term(s)	Animals ; Swine ; Communication ; Epithelial Cells ; Urothelium ; Extracellular Vesicles ; Cell Proliferation ; Extracellular Signal-Regulated MAP Kinases
Chemical Substances	Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2023-08-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-40049-0
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Article ; Online: A database on differentially expressed microRNAs during rodent bladder healing.

Chamorro, Clara Ibel / Eisfeldt, Jesper / Willacy, Oliver / Juul, Nikolai / Fossum, Magdalena

Scientific reports

2021 Volume 11, Issue 1, Page(s) 21881

Abstract: Urinary bladder wound healing relies on multiple biological events that are finely tuned in a spatial-temporal manner. MicroRNAs are small non-coding RNA molecules with regulatory functions. We hypothesized that microRNAs are important molecules in the ... ...

Abstract	Urinary bladder wound healing relies on multiple biological events that are finely tuned in a spatial-temporal manner. MicroRNAs are small non-coding RNA molecules with regulatory functions. We hypothesized that microRNAs are important molecules in the coordination of normal urinary bladder wound healing. We aimed at identifying microRNAs expressed during bladder wound healing using Affymetrix global array for microRNA profiling of the rodent urinary bladder during healing of a surgically created wound. Results were validated in the rat bladders by real-time PCR (RT-PCR) using three of the differentially expressed (DE) microRNAs. The model was thereafter validated in human cells, by measuring the expression of eight of the DE microRNAs upon in vitro wound-healing assays in primary urothelial cells. Our results indicated that 508 (40%) of all rodent microRNAs were expressed in the urinary bladder during wound healing. Thirteen of these microRNAs (1%) were DE (false discovery rate (FDR) < 0.05, P < 0.05, \|logfold\|> 0.25) in wounded compared to non-wounded bladders. Bioinformatic analyses helped us to identify target molecules for the DE microRNAs, and biological pathways involved in tissue repair. All data are made available in an open-access database for other researchers to explore.
MeSH term(s)	Algorithms ; Animals ; Cells, Cultured ; Databases, Nucleic Acid ; Disease Models, Animal ; Gene Expression Profiling ; Humans ; In Vitro Techniques ; Male ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Oligonucleotide Array Sequence Analysis ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Tissue Engineering ; Urinary Bladder/injuries ; Urinary Bladder/metabolism ; Urothelium/cytology ; Urothelium/physiology ; Wound Healing/genetics ; Wound Healing/physiology
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-11-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-01413-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Exploring the Concept of In Vivo Guided Tissue Engineering by a Single-Stage Surgical Procedure in a Rodent Model.

Chamorro, Clara Ibel / Zeiai, Said / Juul, Nikolai / Willacy, Oliver / Huo, Jinxing / Hilborn, Jöns / Fossum, Magdalena

International journal of molecular sciences

2022 Volume 23, Issue 20

Abstract: In severe malformations with a lack of native tissues, treatment options are limited. We aimed at expanding tissue in vivo using the body as a bioreactor and developing a sustainable single-staged procedure for autologous tissue reconstruction in ... ...

Abstract	In severe malformations with a lack of native tissues, treatment options are limited. We aimed at expanding tissue in vivo using the body as a bioreactor and developing a sustainable single-staged procedure for autologous tissue reconstruction in malformation surgery. Autologous micro-epithelium from skin was integrated with plastically compressed collagen and a degradable knitted fabric mesh. Sixty-three scaffolds were implanted in nine rats for histological and mechanical analyses, up to 4 weeks after transplantation. Tissue integration, cell expansion, proliferation, inflammation, strength, and elasticity were evaluated over time in vivo and validated in vitro in a bladder wound healing model. After 5 days in vivo, we observed keratinocyte proliferation on top of the transplant, remodeling of the collagen, and neovascularization within the transplant. At 4 weeks, all transplants were fully integrated with the surrounding tissue. Tensile strength and elasticity were retained during the whole study period. In the in vitro models, a multilayered epithelium covered the defect after 4 weeks. Autologous micro-epithelial transplants allowed for cell expansion and reorganization in vivo without conventional pre-operative in vitro cell propagation. The method was easy to perform and did not require handling outside the operating theater.
MeSH term(s)	Rats ; Animals ; Tissue Engineering/methods ; Rodentia ; Collagen ; Tensile Strength ; Transplantation, Autologous ; Tissue Scaffolds
Chemical Substances	Collagen (9007-34-5)
Language	English
Publishing date	2022-10-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232012703
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Decellularization of the murine cardiopulmonary complex

Mayorca-Guiliani, Alejandro E. / Rafaeva, Maria / Willacy, Oliver / Madsen, Chris D. / Reuten, Raphael / Erler, Janine T.

Journal of visualized experiments. 2021 May 30, , no. 171

2021

Abstract: We present here a decellularization protocol for mouse heart and lungs. It produces structural ECM scaffolds that can be used to analyze ECM topology and composition. It is based on a microsurgical procedure designed to catheterize the trachea and aorta ... ...

Abstract	We present here a decellularization protocol for mouse heart and lungs. It produces structural ECM scaffolds that can be used to analyze ECM topology and composition. It is based on a microsurgical procedure designed to catheterize the trachea and aorta of a euthanized mouse to perfuse the heart and lungs with decellularizing agents. The decellularized cardiopulmonary complex can subsequently be immunostained to reveal the location of structural ECM proteins. The whole procedure can be completed in 4 days. The ECM scaffolds resulting from this protocol are free of dimensional distortions. The absence of cells enables structural examination of ECM structures down to submicron resolution in 3D. This protocol can be applied to healthy and diseased tissue from mice as young as 4-weeks old, including mouse models of fibrosis and cancer, opening the way to determine ECM remodeling associated with cardiopulmonary disease.
Keywords	aorta ; fibrosis ; heart ; mice ; topology
Language	English
Dates of publication	2021-0530
Size	p. e61854.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/61854
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Decellularization of the Murine Cardiopulmonary Complex.

Mayorca-Guiliani, Alejandro E / Rafaeva, Maria / Willacy, Oliver / Madsen, Chris D / Reuten, Raphael / Erler, Janine T

Journal of visualized experiments : JoVE

2021 , Issue 171

Abstract	We present here a decellularization protocol for mouse heart and lungs. It produces structural ECM scaffolds that can be used to analyze ECM topology and composition. It is based on a microsurgical procedure designed to catheterize the trachea and aorta of a euthanized mouse to perfuse the heart and lungs with decellularizing agents. The decellularized cardiopulmonary complex can subsequently be immunostained to reveal the location of structural ECM proteins. The whole procedure can be completed in 4 days. The ECM scaffolds resulting from this protocol are free of dimensional distortions. The absence of cells enables structural examination of ECM structures down to submicron resolution in 3D. This protocol can be applied to healthy and diseased tissue from mice as young as 4-weeks old, including mouse models of fibrosis and cancer, opening the way to determine ECM remodeling associated with cardiopulmonary disease.
MeSH term(s)	Animals ; Extracellular Matrix ; Heart ; Lung ; Mice ; Tissue Engineering ; Tissue Scaffolds
Language	English
Publishing date	2021-05-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/61854
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Author Correction: Decellularization and antibody staining of mouse tissues to map native extracellular matrix structures in 3D.

Mayorca-Guiliani, Alejandro E / Willacy, Oliver / Madsen, Chris D / Rafaeva, Maria / Heumüller, Stefanie Elisabeth / Bock, Felix / Sengle, Gerhard / Koch, Manuel / Imhof, Thomas / Zaucke, Frank / Wagener, Raimund / Sasaki, Takako / Erler, Janine T / Reuten, Raphael

Nature protocols

2020 Volume 15, Issue 6, Page(s) 2140

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Language	English
Publishing date	2020-03-23
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2244966-8
ISSN	1750-2799 ; 1754-2189
ISSN (online)	1750-2799
ISSN	1754-2189
DOI	10.1038/s41596-020-0315-7
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