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A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion
OBJECTIVE: Osteoarthritis is a degenerative disease of the joint, affecting over 30 million people in the US(1). A key characteristic of OA is chondrocyte hypertrophy, characterized by chondrocyte changes to a more rounded and osteoblastic phenotype, characterized by increased IL-6 and IL-8 secretio...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986124/ https://www.ncbi.nlm.nih.gov/pubmed/35392127 http://dx.doi.org/10.1016/j.ocarto.2020.100125 |
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author | Davis, Mollie S. Marrero – Berrios, Ileana Perez, Xiomara I. Radhakrishnan, Palangat Manchikalapati, Devasena Ahmed, Khaja Kamath, Hattiyangangadi Schloss, Rene S. Yarmush, Joel |
author_facet | Davis, Mollie S. Marrero – Berrios, Ileana Perez, Xiomara I. Radhakrishnan, Palangat Manchikalapati, Devasena Ahmed, Khaja Kamath, Hattiyangangadi Schloss, Rene S. Yarmush, Joel |
author_sort | Davis, Mollie S. |
collection | PubMed |
description | OBJECTIVE: Osteoarthritis is a degenerative disease of the joint, affecting over 30 million people in the US(1). A key characteristic of OA is chondrocyte hypertrophy, characterized by chondrocyte changes to a more rounded and osteoblastic phenotype, characterized by increased IL-6 and IL-8 secretion(2). While there are no cures for OA, treatments focus on mitigating pain and inflammation, the two main symptoms of OA. However, the analgesics, NSAIDS and corticosteroids commonly used, do not target regeneration and have negative side effects. Local anesthetics (LA) can be used as a pain management alternative but are usually short lasting and therefore, not suited for chronic conditions such as OA. Our engineered sustained release local anesthetic construct successfully delivers bupivacaine for an extended period of time(3-5). This study is designed to evaluate the effect of the LA system on chondrocytes in an inflammatory OA-like environment. DESIGN: Chondrocytes were cultured with bolus, liposomal, or construct LA and either untreated or treated with TNF-α and IL-1α for 24 hrs, 48 hrs, or 96 hrs. Chondrocyte viability, interleukin-8 (IL-8), interleukin-6 (IL-6), collagenase activity and proteoglycan deposition were assessed. RESULTS: In the presence of the engineered construct, the chondrocytes retained viability and regenerative function. Moreover, the construct allowed for higher initial doses to be used, which promoted more regeneration and decreased inflammation without compromising cellular viability. CONCLUSIONS: The construct promotes a less hypertrophic chondrocyte environment while promoting a more anti-inflammatory environment. These two factors are consistent with a less OA progressive environment when using the engineered construct, compared to bolus LA. |
format | Online Article Text |
id | pubmed-8986124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-89861242022-04-06 A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion Davis, Mollie S. Marrero – Berrios, Ileana Perez, Xiomara I. Radhakrishnan, Palangat Manchikalapati, Devasena Ahmed, Khaja Kamath, Hattiyangangadi Schloss, Rene S. Yarmush, Joel Osteoarthr Cartil Open ORIGINAL PAPER OBJECTIVE: Osteoarthritis is a degenerative disease of the joint, affecting over 30 million people in the US(1). A key characteristic of OA is chondrocyte hypertrophy, characterized by chondrocyte changes to a more rounded and osteoblastic phenotype, characterized by increased IL-6 and IL-8 secretion(2). While there are no cures for OA, treatments focus on mitigating pain and inflammation, the two main symptoms of OA. However, the analgesics, NSAIDS and corticosteroids commonly used, do not target regeneration and have negative side effects. Local anesthetics (LA) can be used as a pain management alternative but are usually short lasting and therefore, not suited for chronic conditions such as OA. Our engineered sustained release local anesthetic construct successfully delivers bupivacaine for an extended period of time(3-5). This study is designed to evaluate the effect of the LA system on chondrocytes in an inflammatory OA-like environment. DESIGN: Chondrocytes were cultured with bolus, liposomal, or construct LA and either untreated or treated with TNF-α and IL-1α for 24 hrs, 48 hrs, or 96 hrs. Chondrocyte viability, interleukin-8 (IL-8), interleukin-6 (IL-6), collagenase activity and proteoglycan deposition were assessed. RESULTS: In the presence of the engineered construct, the chondrocytes retained viability and regenerative function. Moreover, the construct allowed for higher initial doses to be used, which promoted more regeneration and decreased inflammation without compromising cellular viability. CONCLUSIONS: The construct promotes a less hypertrophic chondrocyte environment while promoting a more anti-inflammatory environment. These two factors are consistent with a less OA progressive environment when using the engineered construct, compared to bolus LA. Elsevier 2020-11-19 /pmc/articles/PMC8986124/ /pubmed/35392127 http://dx.doi.org/10.1016/j.ocarto.2020.100125 Text en © 2020 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | ORIGINAL PAPER Davis, Mollie S. Marrero – Berrios, Ileana Perez, Xiomara I. Radhakrishnan, Palangat Manchikalapati, Devasena Ahmed, Khaja Kamath, Hattiyangangadi Schloss, Rene S. Yarmush, Joel A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion |
title | A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion |
title_full | A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion |
title_fullStr | A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion |
title_full_unstemmed | A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion |
title_short | A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion |
title_sort | controlled release bupivacaine-alginate construct: effect on chondrocyte hypertrophy conversion |
topic | ORIGINAL PAPER |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986124/ https://www.ncbi.nlm.nih.gov/pubmed/35392127 http://dx.doi.org/10.1016/j.ocarto.2020.100125 |
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