Thermosensitive hydrogels deliver bioactive protein to the vaginal wall.
The pathophysiology and natural history of pelvic organ prolapse (POP) are poorly understood. Consequently, our approaches to treatment of POP are limited. Alterations in the extracellular matrix components of pelvic support ligaments and vaginal tissue, including collagen and elastin, have been ass...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5657977?pdf=render |
| _version_ | 1818293375345885184 |
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| author | Meadow M Good T Ignacio Montoya Haolin Shi Jun Zhou YiHui Huang Liping Tang Jesus F Acevedo R Ann Word |
| author_facet | Meadow M Good T Ignacio Montoya Haolin Shi Jun Zhou YiHui Huang Liping Tang Jesus F Acevedo R Ann Word |
| author_sort | Meadow M Good |
| collection | DOAJ |
| description | The pathophysiology and natural history of pelvic organ prolapse (POP) are poorly understood. Consequently, our approaches to treatment of POP are limited. Alterations in the extracellular matrix components of pelvic support ligaments and vaginal tissue, including collagen and elastin, have been associated with the development of POP in animals and women. Prior studies have shown the protease MMP-9, a key player of ECM degradation, is upregulated in vaginal tissues from both mice and women with POP. On the other hand, fibulin-5, an elastogenic organizer, has been found to inhibit MMP-9 in the vaginal wall. Hence, we hypothesized that prolonged release of fibulin-5 may delay progression of POP. To test the hypothesis, oligo (ethylene glycol)-based thermosensitive hydrogels were fabricated, characterized and then used to deliver fibulin-5 to the vaginal wall and inhibit MMP-9 activity. The results indicate that hydrogels are cell and tissue compatible. The hydrogels also prolong the ½ life of fibulin-5 in cultured vaginal fibroblasts and in the vaginal wall in vivo. Finally, fibulin-5-containing hydrogels resulted in incorporation of fibulin-5 into the vaginal matrix and inhibition of MMP-9 for several weeks after injection. These results support the idea of fibulin-5 releasing hydrogel being developed as a new treatment for POP. |
| first_indexed | 2024-12-13T03:14:51Z |
| format | Article |
| id | doaj.art-3e8aea7098bf43e3966f20652a0e6851 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T03:14:51Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3e8aea7098bf43e3966f20652a0e68512022-12-22T00:01:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011210e018626810.1371/journal.pone.0186268Thermosensitive hydrogels deliver bioactive protein to the vaginal wall.Meadow M GoodT Ignacio MontoyaHaolin ShiJun ZhouYiHui HuangLiping TangJesus F AcevedoR Ann WordThe pathophysiology and natural history of pelvic organ prolapse (POP) are poorly understood. Consequently, our approaches to treatment of POP are limited. Alterations in the extracellular matrix components of pelvic support ligaments and vaginal tissue, including collagen and elastin, have been associated with the development of POP in animals and women. Prior studies have shown the protease MMP-9, a key player of ECM degradation, is upregulated in vaginal tissues from both mice and women with POP. On the other hand, fibulin-5, an elastogenic organizer, has been found to inhibit MMP-9 in the vaginal wall. Hence, we hypothesized that prolonged release of fibulin-5 may delay progression of POP. To test the hypothesis, oligo (ethylene glycol)-based thermosensitive hydrogels were fabricated, characterized and then used to deliver fibulin-5 to the vaginal wall and inhibit MMP-9 activity. The results indicate that hydrogels are cell and tissue compatible. The hydrogels also prolong the ½ life of fibulin-5 in cultured vaginal fibroblasts and in the vaginal wall in vivo. Finally, fibulin-5-containing hydrogels resulted in incorporation of fibulin-5 into the vaginal matrix and inhibition of MMP-9 for several weeks after injection. These results support the idea of fibulin-5 releasing hydrogel being developed as a new treatment for POP.http://europepmc.org/articles/PMC5657977?pdf=render |
| spellingShingle | Meadow M Good T Ignacio Montoya Haolin Shi Jun Zhou YiHui Huang Liping Tang Jesus F Acevedo R Ann Word Thermosensitive hydrogels deliver bioactive protein to the vaginal wall. PLoS ONE |
| title | Thermosensitive hydrogels deliver bioactive protein to the vaginal wall. |
| title_full | Thermosensitive hydrogels deliver bioactive protein to the vaginal wall. |
| title_fullStr | Thermosensitive hydrogels deliver bioactive protein to the vaginal wall. |
| title_full_unstemmed | Thermosensitive hydrogels deliver bioactive protein to the vaginal wall. |
| title_short | Thermosensitive hydrogels deliver bioactive protein to the vaginal wall. |
| title_sort | thermosensitive hydrogels deliver bioactive protein to the vaginal wall |
| url | http://europepmc.org/articles/PMC5657977?pdf=render |
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