Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus.
Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus.
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具有 KGF 亲和力的温敏肝素修饰泊洛沙姆水凝胶促进受损大鼠子宫形态和功能恢复
DOI：
10.1080/10717544.2017.1333173
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发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Zhao YZ
中科院分区：
文献类型：
--
作者：
Xu HL;Xu J;Zhang SS;Zhu QY;Jin BH;ZhuGe DL;Shen BX;Wu XQ;Xiao J;Zhao YZ
子宫内膜损伤通常会导致宫腔粘连（IUA），这是育龄妇女不孕和反复流产的重要原因。目前仍缺乏有效的治疗策略来预防IUA的发生。角质形成细胞生长因子（KGF）是上皮组织的有效修复因子。在这里，具有 KGF 亲和力的温度敏感肝素修饰泊洛沙姆 (HP) 水凝胶 (KGF-HP) 被用作支持基质，以防止 IUA 并递送 KGF。 KGF-HP 水凝胶的流变学经过仔细表征。冷的KGF-HP溶液在33°C的温度下迅速转变为具有合适的储能模量（G'）和损耗模量（G''）的水凝胶，用于子宫腔的应用。体外释放表明KGF以缓释方式从HP水凝胶中长时间释放。体内生物发光成像表明，KGF-HP 水凝胶能够延长封装的 KGF 在大鼠模型受损子宫中的保留时间。此外，通过二维超声成像和受孕能力评估，施用KGF-HP水凝胶后受损子宫的形态和功能显着恢复。 KGF-HP水凝胶处理7天后，通过Ki67和CD31染色不仅观察到子宫内膜腺上皮细胞和管腔上皮细胞的增殖，还观察到受损子宫的血管生成。最后，通过检测KGF处理后LC3-II和P62的表达，首次证实自噬与子宫内膜上皮细胞（EEC）增殖和血管生成之间存在密切的相对关系。总体而言，KGF-HP 可能作为 IUA 治疗的有希望的候选者。
Endometrial injury usually results in intrauterine adhesion (IUA), which is an important cause of infertility and recurrent miscarriage in reproductive women. There is still lack of an effective therapeutic strategy to prevent occurrence of IUA. Keratinocyte growth factor (KGF) is a potent repair factor for epithelial tissues. Here, a temperature-sensitive heparin-modified poloxamer (HP) hydrogel with affinity to KGF (KGF-HP) was used as a support matrix to prevent IUA and deliver KGF. The rheology of KGF-HP hydrogel was carefully characterized. The cold KGF-HP solution was rapidly transited to hydrogel with suitable storage modulus (G′) and loss modulus (G″) for the applications of uterus cavity at temperature of 33 °C. In vitro release demonstrated that KGF was released from HP hydrogels in sustained release manner for a long time. In vivo bioluminescence imaging showed that KGF-HP hydrogel was able to prolong the retention of the encapsulated KGF in injured uterus of rat model. Moreover, the morphology and function of the injured uterus were significantly recovered after administration of KGF-HP hydrogel, which were evaluated by two-dimensional ultrasound imaging and receptive fertility. Not only proliferation of endometrial glandular epithelial cells and luminal epithelial cells but also angiogenesis of injured uterus were observed by Ki67 and CD31 staining after 7 d of treatment with KGF-HP hydrogel. Finally, a close relatively relationship between autophagy and proliferation of endometrial epithelial cells (EEC) and angiogenesis was firstly confirmed by detecting expression of LC3-II and P62 after KGF treatment. Overall, KGF-HP may be used as a promising candidate for IUA treatment.
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影响因子：
9.2
作者：
Lin X;Zhang Y;Liu L;McKeehan WL;Shen Y;Song S;Wang F
通讯作者：
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作者：
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作者：
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作者：
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