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具有高细胞黏附活性的可注射重组人胶原蛋白衍生材料可限制盆底功能障碍大鼠的不良重塑,改善盆底功能。

Injectable recombinant human collagen-derived material with high cell adhesion activity limits adverse remodelling and improves pelvic floor function in pelvic floor dysfunction rats.

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.

Fudan-Jinbo Joint Research Center, Fudan University, Shanghai 200302, China.

出版信息

Biomater Adv. 2022 Mar;134:112715. doi: 10.1016/j.msec.2022.112715. Epub 2022 Feb 12.

Abstract

Female pelvic floor dysfunction (FPFD) is a life-changing condition that severely affects women's physical and mental health. Despite the effectiveness of current treatments for FPFD, there is a high rate of short-term recurrence. Here, we introduced an injectable recombinant human collagen (rhCOL)-derived material with high cell adhesion activity to achieve pelvic floor repair and extracellular matrix (ECM) assembly. In our study, rhCOL promoted human uterosacral ligament fibroblast (HULF) adhesion, migration, and collagen I and III expression and regulated the metabolism of HULFs in vitro. Subsequently, we established a rat model of FPFD. Then, rhCOL, including rhCOLI and rhCOLIII, was perivaginally injected into FPFD rats, resulting in a significant increase in abdominal urine leak point pressure (LPP) and maximum tensile strength compared to the FPFD model group. Better organization of the lamina propria and muscularis in FPFD rats was observed after 14 days of rhCOL treatment. Meanwhile, the expression of collagen I, collagen III, and TIMP1 was upregulated, and MMP2 was downregulated. Furthermore, rhCOL promoted HULF adhesion, migration, and ECM synthesis by upregulating the focal adhesion kinase (FAK)/RhoA/ROCK signalling pathway in vitro and in vivo. These findings suggest that the perivaginal injection of rhCOL is a promising treatment for FPFD with potential for future clinical use.

摘要

女性盆底功能障碍(FPFD)是一种改变生活的疾病,严重影响着女性的身心健康。尽管目前 FPFD 的治疗方法有效,但短期复发率很高。在这里,我们介绍了一种可注射的重组人胶原蛋白(rhCOL)衍生的具有高细胞黏附活性的材料,以实现盆底修复和细胞外基质(ECM)组装。在我们的研究中,rhCOL 促进了人子宫骶韧带成纤维细胞(HULF)的黏附、迁移和胶原 I 和 III 的表达,并调节了 HULFs 的代谢。随后,我们建立了 FPFD 大鼠模型。然后,rhCOL(包括 rhCOLI 和 rhCOLIII)经阴道周围注射到 FPFD 大鼠中,与 FPFD 模型组相比,大鼠的腹压漏点压(LPP)和最大拉伸强度显著增加。rhCOL 治疗 14 天后,FPFD 大鼠的固有层和肌层组织得到了更好的组织。同时,胶原 I、胶原 III 和 TIMP1 的表达上调,MMP2 的表达下调。此外,rhCOL 通过上调体外和体内黏着斑激酶(FAK)/RhoA/ROCK 信号通路促进 HULF 的黏附、迁移和 ECM 合成。这些发现表明,rhCOL 的阴道周围注射是治疗 FPFD 的一种很有前途的方法,具有潜在的临床应用前景。

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