Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/143484 |
Resumo: | Cartilage repair still represents a challenge for clinicians and only few effective therapies are nowadays available. In fact, surgery is limited by the tissue poor self-healing capacity while the autologous transplantation is often forsaken due to the poor in vitro expansion capacity of chondrocytes. Biomaterials science offers a unique alternative based on the replacement of the injured tissue with an artificial tissue-mimicking scaffold. However, the implantation surgical practices and the scaffold itself can be a source of bacterial infection that currently represents the first reason of implants failure due to the increasing antibiotics resistance of pathogens. So, alternative antibacterial tools to prevent infections and consequent device removal are urgently required. In this work, the role of Nisin and LL-37 peptides has been investigated as alternative to antibiotics to their antimicrobial performances for direct application at the surgical site or as doping chemicals for devices aimed at articular cartilage repair. First, peptides cytocompatibility was investigated toward human mesenchymal stem cells to determine safe concentrations; then, the broad-range antibacterial activity was verified toward the Gram-positive Staphylococcus aureus and Staphylococcus epidermidis as well as the Gram-negative Escherichia coli and Aggregatibacter actinomycetemcomitans pathogens. The peptides selective antibacterial activity was verified by a cells-bacteria co-culture assay, while chondrogenesis was assayed to exclude any interference within the differentiation route to simulate the tissue repair. In the next phase, the experiments were repeated by moving from the cell monolayer model to 3D cartilage-like spheroids to revisit the peptides activity in a more physiologically relevant environment model. Finally, the spheroid model was applied in a perfusion bioreactor to simulate an infection in the presence of circulating peptides within a physiological environment. Results suggested that 75 µg/ml Nisin can be considered as a very promising candidate since it was shown to be more cytocompatible and potent against the investigated bacteria than LL-37 in all the tested models. |
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Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environmentAntibacterial studyAntimicrobial peptidesBioreactorCo-culturesHuman mesenchymal stem cellsPro-chondrogenic agentsCartilage repair still represents a challenge for clinicians and only few effective therapies are nowadays available. In fact, surgery is limited by the tissue poor self-healing capacity while the autologous transplantation is often forsaken due to the poor in vitro expansion capacity of chondrocytes. Biomaterials science offers a unique alternative based on the replacement of the injured tissue with an artificial tissue-mimicking scaffold. However, the implantation surgical practices and the scaffold itself can be a source of bacterial infection that currently represents the first reason of implants failure due to the increasing antibiotics resistance of pathogens. So, alternative antibacterial tools to prevent infections and consequent device removal are urgently required. In this work, the role of Nisin and LL-37 peptides has been investigated as alternative to antibiotics to their antimicrobial performances for direct application at the surgical site or as doping chemicals for devices aimed at articular cartilage repair. First, peptides cytocompatibility was investigated toward human mesenchymal stem cells to determine safe concentrations; then, the broad-range antibacterial activity was verified toward the Gram-positive Staphylococcus aureus and Staphylococcus epidermidis as well as the Gram-negative Escherichia coli and Aggregatibacter actinomycetemcomitans pathogens. The peptides selective antibacterial activity was verified by a cells-bacteria co-culture assay, while chondrogenesis was assayed to exclude any interference within the differentiation route to simulate the tissue repair. In the next phase, the experiments were repeated by moving from the cell monolayer model to 3D cartilage-like spheroids to revisit the peptides activity in a more physiologically relevant environment model. Finally, the spheroid model was applied in a perfusion bioreactor to simulate an infection in the presence of circulating peptides within a physiological environment. Results suggested that 75 µg/ml Nisin can be considered as a very promising candidate since it was shown to be more cytocompatible and potent against the investigated bacteria than LL-37 in all the tested models.Frontiers Media20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/143484eng2296-418510.3389/fbioe.2020.00561Najmi, ZKumar, AScalia, ACCochis, AObradovic, BGrassi, FALeigheb, MLamghari, MLoinaz, IGracia, RRimondini, Linfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T15:10:57Zoai:repositorio-aberto.up.pt:10216/143484Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:17:35.012080Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment |
title |
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment |
spellingShingle |
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment Najmi, Z Antibacterial study Antimicrobial peptides Bioreactor Co-cultures Human mesenchymal stem cells Pro-chondrogenic agents |
title_short |
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment |
title_full |
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment |
title_fullStr |
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment |
title_full_unstemmed |
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment |
title_sort |
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment |
author |
Najmi, Z |
author_facet |
Najmi, Z Kumar, A Scalia, AC Cochis, A Obradovic, B Grassi, FA Leigheb, M Lamghari, M Loinaz, I Gracia, R Rimondini, L |
author_role |
author |
author2 |
Kumar, A Scalia, AC Cochis, A Obradovic, B Grassi, FA Leigheb, M Lamghari, M Loinaz, I Gracia, R Rimondini, L |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Najmi, Z Kumar, A Scalia, AC Cochis, A Obradovic, B Grassi, FA Leigheb, M Lamghari, M Loinaz, I Gracia, R Rimondini, L |
dc.subject.por.fl_str_mv |
Antibacterial study Antimicrobial peptides Bioreactor Co-cultures Human mesenchymal stem cells Pro-chondrogenic agents |
topic |
Antibacterial study Antimicrobial peptides Bioreactor Co-cultures Human mesenchymal stem cells Pro-chondrogenic agents |
description |
Cartilage repair still represents a challenge for clinicians and only few effective therapies are nowadays available. In fact, surgery is limited by the tissue poor self-healing capacity while the autologous transplantation is often forsaken due to the poor in vitro expansion capacity of chondrocytes. Biomaterials science offers a unique alternative based on the replacement of the injured tissue with an artificial tissue-mimicking scaffold. However, the implantation surgical practices and the scaffold itself can be a source of bacterial infection that currently represents the first reason of implants failure due to the increasing antibiotics resistance of pathogens. So, alternative antibacterial tools to prevent infections and consequent device removal are urgently required. In this work, the role of Nisin and LL-37 peptides has been investigated as alternative to antibiotics to their antimicrobial performances for direct application at the surgical site or as doping chemicals for devices aimed at articular cartilage repair. First, peptides cytocompatibility was investigated toward human mesenchymal stem cells to determine safe concentrations; then, the broad-range antibacterial activity was verified toward the Gram-positive Staphylococcus aureus and Staphylococcus epidermidis as well as the Gram-negative Escherichia coli and Aggregatibacter actinomycetemcomitans pathogens. The peptides selective antibacterial activity was verified by a cells-bacteria co-culture assay, while chondrogenesis was assayed to exclude any interference within the differentiation route to simulate the tissue repair. In the next phase, the experiments were repeated by moving from the cell monolayer model to 3D cartilage-like spheroids to revisit the peptides activity in a more physiologically relevant environment model. Finally, the spheroid model was applied in a perfusion bioreactor to simulate an infection in the presence of circulating peptides within a physiological environment. Results suggested that 75 µg/ml Nisin can be considered as a very promising candidate since it was shown to be more cytocompatible and potent against the investigated bacteria than LL-37 in all the tested models. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/143484 |
url |
https://hdl.handle.net/10216/143484 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2296-4185 10.3389/fbioe.2020.00561 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799136095193006080 |