A thermo-sensitive and injectable hydrogel derived from a decellularized amniotic membrane to prevent intrauterine adhesion by accelerating endometrium regeneration

Xiaoyu Li; Peilin Li; Can Wang; Ting Shang; Haotian Han; Yongjuan Tong; Yubin Kang; Jianjun Fang; Lei Cui

doi:10.1039/D1BM01791H

A thermo-sensitive and injectable hydrogel derived from a decellularized amniotic membrane to prevent intrauterine adhesion by accelerating endometrium regeneration†

Xiaoyu Li,‡^a Peilin Li,

‡^a Can Wang,

^b Ting Shang,^a Haotian Han,^a Yongjuan Tong,^c Yubin Kang,^a Jianjun Fang*^d and Lei Cui

*^ae

Author affiliations

* Corresponding authors

^a Department of Plastic and Cosmetic Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
E-mail: cuilei8890@bjsjth.cn
Tel: +86 (10) 63926418

^b Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China

^c Central Laboratory, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China

^d Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of the Ministry of Education, Hunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China
E-mail: fang_88088@163.com
Tel: +86 (731) 58290455

^e Key Laboratory of Aesthetics Medicine, Chinese Association of Plastic and Aesthetics, Beijing 100038, China

Abstract

Objective To investigate the effect of the injectable hydrogel generated from a decellularized amniotic membrane (dAM)-gel on preventing the development of an intrauterine adhesion (IUA) on a rat model. Methods The dAM-gel was developed from an amniotic membrane (AM) by a process of decellularization, lyophilization, and enzyme digestion. Histological analysis, residual component determination, electronic microscopy and turbidimetric gelation kinetics analysis were performed to characterize the dAM-gel. The proliferation and migration of endometrial cells on the dAM-gel coated surface was examined. IUA was surgically created in rats and received dAM-gel injection immediately after wound creation. Gene profiles of epithelial cells cultured on the dAM-gel coated surface were evaluated by RNA-sequencing. Results The collagen content was retained in the dAM-gel, while the GAG content decreased significantly compared with fresh AM (fAM). Gelation of the gel was temperature-sensitive and showed a matrix concentration-dependent manner. Transplantation of the dAM-gel significantly reduced fibrosis of IUA with a recovered uterine cavity, regenerated endometrium and increased microvascular density, along with elevated pregnancy rate compared with endometrium damage groups. Migration of epithelial cells was greatly promoted by the dAM-gel in a surgically created uterine wound model. By comparing the RNA-sequence data of epithelial cells that were cultured on dAM-gel coated and non-coated surfaces, respectively, distinct gene profiles relative to the cellular migration, adhesion and angiogenesis and involved signaling pathway were identified. Conclusions The injectable dAM-gel developed from AM offers a promising option for preventing endometrial fibrosis by promotion of the re-epithelialization of the damaged endometrium.

Biomaterials Science

A thermo-sensitive and injectable hydrogel derived from a decellularized amniotic membrane to prevent intrauterine adhesion by accelerating endometrium regeneration†

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A thermo-sensitive and injectable hydrogel derived from a decellularized amniotic membrane to prevent intrauterine adhesion by accelerating endometrium regeneration

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