Cargando…

Report on a large animal study with Göttingen Minipigs where regenerates and controls for articular cartilage were created in a large number. Focus on the conditions of the operated stifle joints and suggestions for standardized procedures

The characterization of regenerated articular cartilage (AC) can be based on various methods, as there is an unambiguous accepted criterion neither for the natural cartilage tissue nor for regenerates. Biomechanical aspects should be considered as well, leading to the need for more equivalent sample...

Descripción completa

Detalles Bibliográficos
Autores principales: Schwarz, Markus L., Reisig, Gregor, Schütte, Andy, Becker, Kristianna, Serba, Susanne, Forsch, Elmar, Thier, Steffen, Fickert, Stefan, Lenz, Tamara, Weiß, Christel, Hetjens, Svetlana, Bludau, Frederic, Bothe, Friederike, Richter, Wiltrud, Schneider-Wald, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932782/
https://www.ncbi.nlm.nih.gov/pubmed/31877143
http://dx.doi.org/10.1371/journal.pone.0224996
_version_ 1783483074852421632
author Schwarz, Markus L.
Reisig, Gregor
Schütte, Andy
Becker, Kristianna
Serba, Susanne
Forsch, Elmar
Thier, Steffen
Fickert, Stefan
Lenz, Tamara
Weiß, Christel
Hetjens, Svetlana
Bludau, Frederic
Bothe, Friederike
Richter, Wiltrud
Schneider-Wald, Barbara
author_facet Schwarz, Markus L.
Reisig, Gregor
Schütte, Andy
Becker, Kristianna
Serba, Susanne
Forsch, Elmar
Thier, Steffen
Fickert, Stefan
Lenz, Tamara
Weiß, Christel
Hetjens, Svetlana
Bludau, Frederic
Bothe, Friederike
Richter, Wiltrud
Schneider-Wald, Barbara
author_sort Schwarz, Markus L.
collection PubMed
description The characterization of regenerated articular cartilage (AC) can be based on various methods, as there is an unambiguous accepted criterion neither for the natural cartilage tissue nor for regenerates. Biomechanical aspects should be considered as well, leading to the need for more equivalent samples. The aim of the study was to describe a large animal model where 8 specimens of regenerated AC can be created in one animal plus the impact of two surgeries on the welfare of the animals. The usefulness of the inclusion of a group of untreated animals (NAT) was to analyzed. Based on the histological results the conditions of the regenerates were to be described and the impact on knee joints were to be explored in terms of degenerative changes of the cartilage. The usefulness of the statistical term “effect size” (ES) will be explained with histological results. We analyzed an animal model where 8 AC regenerates were obtained from one Göttingen Minipig, on both sides of the trochleae. 60 animals were divided into 6 groups of 10 each, where the partial thickness defects in the trochlea were filled with matrices made of Collagen I with or without autologous chondrocytes or left empty over the healing periods of 24 and 48 weeks. One additional control group consisting of 10 untreated animals was used to provide untouched “external” cartilage. We harvested 560 samples of regenerated tissue and “external” controls, besides that, twice the number of further samples from other parts of the joints referred to as “internal” controls were also harvested. The animals recovered faster after the 1(st) operation when the defects were set compared to the 2(nd) operation when the defects were treated. 9% of all animals were lost. Other complications were for example superficial infections, seroma, diarrhea, febrile state and an injury of a claw. The histological results of the treatments proved the robustness of the study design where we included an “external” control group (NAT) in which the animals were not operated. Comparable significant differences between treated groups and the NAT group were detected both after ½ year and after 1 year. Spontaneous regenerated AC as control revealed differences after an observation time of nearly 1 year. The impact of the treatment on cartilage adjacent to the defect as well as the remaining knee joint was low. The ES was helpful for planning the study as it is shown that the power of a statistical comparison seems to be more influenced by the ES than by the sample size. The ranking of the ES was done exemplarily, listing the results according to their magnitude, thus making the results comparable. We were able to follow the 3 R requirements also in terms of a numerical reduction of animals due to the introduction of a group of untreated animals. This makes the model cost effective. The presented study may contribute as an improvement of the standardization of large animal models for research and regulatory requirements for regenerative therapies of AC.
format Online
Article
Text
id pubmed-6932782
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-69327822020-01-07 Report on a large animal study with Göttingen Minipigs where regenerates and controls for articular cartilage were created in a large number. Focus on the conditions of the operated stifle joints and suggestions for standardized procedures Schwarz, Markus L. Reisig, Gregor Schütte, Andy Becker, Kristianna Serba, Susanne Forsch, Elmar Thier, Steffen Fickert, Stefan Lenz, Tamara Weiß, Christel Hetjens, Svetlana Bludau, Frederic Bothe, Friederike Richter, Wiltrud Schneider-Wald, Barbara PLoS One Research Article The characterization of regenerated articular cartilage (AC) can be based on various methods, as there is an unambiguous accepted criterion neither for the natural cartilage tissue nor for regenerates. Biomechanical aspects should be considered as well, leading to the need for more equivalent samples. The aim of the study was to describe a large animal model where 8 specimens of regenerated AC can be created in one animal plus the impact of two surgeries on the welfare of the animals. The usefulness of the inclusion of a group of untreated animals (NAT) was to analyzed. Based on the histological results the conditions of the regenerates were to be described and the impact on knee joints were to be explored in terms of degenerative changes of the cartilage. The usefulness of the statistical term “effect size” (ES) will be explained with histological results. We analyzed an animal model where 8 AC regenerates were obtained from one Göttingen Minipig, on both sides of the trochleae. 60 animals were divided into 6 groups of 10 each, where the partial thickness defects in the trochlea were filled with matrices made of Collagen I with or without autologous chondrocytes or left empty over the healing periods of 24 and 48 weeks. One additional control group consisting of 10 untreated animals was used to provide untouched “external” cartilage. We harvested 560 samples of regenerated tissue and “external” controls, besides that, twice the number of further samples from other parts of the joints referred to as “internal” controls were also harvested. The animals recovered faster after the 1(st) operation when the defects were set compared to the 2(nd) operation when the defects were treated. 9% of all animals were lost. Other complications were for example superficial infections, seroma, diarrhea, febrile state and an injury of a claw. The histological results of the treatments proved the robustness of the study design where we included an “external” control group (NAT) in which the animals were not operated. Comparable significant differences between treated groups and the NAT group were detected both after ½ year and after 1 year. Spontaneous regenerated AC as control revealed differences after an observation time of nearly 1 year. The impact of the treatment on cartilage adjacent to the defect as well as the remaining knee joint was low. The ES was helpful for planning the study as it is shown that the power of a statistical comparison seems to be more influenced by the ES than by the sample size. The ranking of the ES was done exemplarily, listing the results according to their magnitude, thus making the results comparable. We were able to follow the 3 R requirements also in terms of a numerical reduction of animals due to the introduction of a group of untreated animals. This makes the model cost effective. The presented study may contribute as an improvement of the standardization of large animal models for research and regulatory requirements for regenerative therapies of AC. Public Library of Science 2019-12-26 /pmc/articles/PMC6932782/ /pubmed/31877143 http://dx.doi.org/10.1371/journal.pone.0224996 Text en © 2019 Schwarz et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Schwarz, Markus L.
Reisig, Gregor
Schütte, Andy
Becker, Kristianna
Serba, Susanne
Forsch, Elmar
Thier, Steffen
Fickert, Stefan
Lenz, Tamara
Weiß, Christel
Hetjens, Svetlana
Bludau, Frederic
Bothe, Friederike
Richter, Wiltrud
Schneider-Wald, Barbara
Report on a large animal study with Göttingen Minipigs where regenerates and controls for articular cartilage were created in a large number. Focus on the conditions of the operated stifle joints and suggestions for standardized procedures
title Report on a large animal study with Göttingen Minipigs where regenerates and controls for articular cartilage were created in a large number. Focus on the conditions of the operated stifle joints and suggestions for standardized procedures
title_full Report on a large animal study with Göttingen Minipigs where regenerates and controls for articular cartilage were created in a large number. Focus on the conditions of the operated stifle joints and suggestions for standardized procedures
title_fullStr Report on a large animal study with Göttingen Minipigs where regenerates and controls for articular cartilage were created in a large number. Focus on the conditions of the operated stifle joints and suggestions for standardized procedures
title_full_unstemmed Report on a large animal study with Göttingen Minipigs where regenerates and controls for articular cartilage were created in a large number. Focus on the conditions of the operated stifle joints and suggestions for standardized procedures
title_short Report on a large animal study with Göttingen Minipigs where regenerates and controls for articular cartilage were created in a large number. Focus on the conditions of the operated stifle joints and suggestions for standardized procedures
title_sort report on a large animal study with göttingen minipigs where regenerates and controls for articular cartilage were created in a large number. focus on the conditions of the operated stifle joints and suggestions for standardized procedures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932782/
https://www.ncbi.nlm.nih.gov/pubmed/31877143
http://dx.doi.org/10.1371/journal.pone.0224996
work_keys_str_mv AT schwarzmarkusl reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT reisiggregor reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT schutteandy reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT beckerkristianna reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT serbasusanne reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT forschelmar reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT thiersteffen reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT fickertstefan reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT lenztamara reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT weißchristel reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT hetjenssvetlana reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT bludaufrederic reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT bothefriederike reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT richterwiltrud reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures
AT schneiderwaldbarbara reportonalargeanimalstudywithgottingenminipigswhereregeneratesandcontrolsforarticularcartilagewerecreatedinalargenumberfocusontheconditionsoftheoperatedstiflejointsandsuggestionsforstandardizedprocedures