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Preparation of Fibroblast Suppressive Poly(ethylene glycol)-b-poly(l-phenylalanine)/Poly(ethylene glycol) Hydrogel and Its Application in Intrauterine Fibrosis Prevention
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-12-07 , DOI: 10.1021/acsbiomaterials.0c01390
Bing Wang 1 , Chengmin Feng 2 , Jiafeng Dang 3 , Yanghui Zhu 4 , Xiaomei Yang 5 , Ting Zhang 5 , Ruqin Zhang 5 , Jiawen Li 5 , Jing Tang 5 , Chengyi Shen 6 , Lunhua Shen 7 , Jun Dong 8 , Xiaoming Zhang 9
Affiliation  

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.

中文翻译:

抑制成纤维细胞的聚乙二醇-b-聚苯丙氨酸/聚乙二醇水凝胶的制备及其在宫内纤维化预防中的应用

宫内粘连(IUA)通常是刮宫,产后出血或手术流产后基底层受到创伤的结果。子宫内膜纤维化是IUA的主要病理特征。IUA的特征包括细胞外基质的过度沉积和重组,取代了正常的子宫内膜。为了防止受伤后子宫纤维化,我们准备并评估了一种成纤维细胞抑制水凝胶。通过l的开环聚合成功地合成了聚乙二醇-b-l-苯丙氨酸(PEBP)共聚物-由甲氧基-聚(乙二醇)-胺引发的苯丙氨酸N-羧基酐。随后,通过PEBP大分子之间的π-π堆积以及PEBP,PEG和H 2 O分子之间的氢键形成了可注射的PEBP / PEG水凝胶。PEBP / PEG水凝胶可通过l的作用抑制成纤维细胞的增殖-Phe,从PEBP / PEG凝胶中可持续释放。最后,在大鼠刮宫模型中评估了PEBP / PEG水凝胶对纤维化的体内预防作用。发现PEBP / PEG水凝胶通过调节转化生长因子β1(TGF-β1)和Muc-4的表达和相互作用来抑制刮宫引起的子宫纤维化,并促进受损子宫的胚胎着床。PEBP / PEG水凝胶具有预防纤维化和促进损伤后子宫组织妊娠的作用,因此有可能在子宫粘连的预防中应用。
更新日期:2021-01-11
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