Thermosensitive hydrogels deliver bioactive protein to the vaginal wall

Meadow M. Good, T. Ignacio Montoya, Haolin Shi, Jun Zhou, Yi Hui Huang, Liping Tang, Jesus F. Acevedo, R. Ann Word

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere0186268
JournalPloS one
Volume12
Issue number10
DOIs
StatePublished - Oct 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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  • Cite this

    Good, M. M., Montoya, T. I., Shi, H., Zhou, J., Huang, Y. H., Tang, L., Acevedo, J. F., & Word, R. A. (2017). Thermosensitive hydrogels deliver bioactive protein to the vaginal wall. PloS one, 12(10), [e0186268]. https://doi.org/10.1371/journal.pone.0186268