Intrauterine
adhesions (IUA) often occur as a result of trauma
to the basal layer after curettage, postpartum hemorrhage, or surgical
miscarriage. Endometrial fibrosis is the primary pathological feature
of IUA. The characteristic features of IUA include excessive deposition
and reorganization of the extracellular matrix, replacing the normal
endometrium. To prevent uterine fibrosis after injury, we prepared
and evaluated a type of fibroblast suppressive hydrogel. Poly(ethylene
glycol)-b-poly(l-phenylalanine) (PEBP) copolymers
were successfully synthesized by ring opening polymerization of l-Phenylalanine N-carboxyanhydride, initiated by methoxy-poly(ethylene
glycol)-amine. Injectable PEBP/PEG hydrogels were subsequently formed
through π–π accumulations between PEBP macromolecules
and hydrogen bonds among PEBP, PEG, and H2O molecules.
PEBP/PEG hydrogel could suppress the proliferation of fibroblasts
due to the action of l-Phe, released sustainably from PEBP/PEG
gels. Lastly, the in vivo preventive effect of PEBP/PEG hydrogel on
fibrosis was evaluated in a rat uterine curettage model. It was found
that PEBP/PEG hydrogel suppressed uterine fibrosis caused by curettage
and promoted embryo implantation in injured uterine by regulating
the expression and interactions of transforming growth factor beta
1 (TGF-β1) and Muc-4. PEBP/PEG hydrogels have the potential
for application in uterine adhesion prevention owing to their fibrosis
preventive and pregnancy promotiing effects on uterine tissue after
injury.
Postoperative adhesion is a common complication and preventing adhesions during or immediately after operation is particularly important. The application of solid barrier materials represents the most successful clinical strategy to prevent postoperative adhesion. However, a simple physical barrier effect might be insufficient in preventing adhesion satisfactorily. Multilayered structures can be designed with an outer layer as the barrier and an inner layer to respond to relative drug release. In this article, bilayer film composed of a PLGA/PLCA casting layer as barrier and PLGA/PDPA electrospinning layer to respond to the release of anti-fibrosis drug L-Phe was designed and synthesized. The adhesion prevention effect of the above PLGA/PLCA/PDPA bilayer film was examined and compared with single PLGA/PLCA casting film and single PLGA/PDPA electrospinning film by applying rabbit sidewall defect-cecum abrasion model. As demonstrated by histological observation and immunohistochemical analysis, the bilayer film was the most effective of the three films in postoperative adhesion prevention in terms of both physical barrier effect and anti-fibrosis effect of the PDPA macromolecular prodrug. Besides anti-fibrosis effect, PDPA could also suppress excess proliferation of vascular endothelial cells and microvessel caused by long-term stimulation of implantation materials to the surrounding tissues.
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