Injectable “Homing‐Like” Bioactive Short‐Fibers for Endometrial Repair and Efficient Live Births

Author:

Cao Yumeng12,Qi Jia12,Wang Juan3,Chen Liang3,Wang Yuan12,Long Yijing12,Li Boyu12,Lai Junliang12,Yao Yejie12,Meng Yiwen12,Yu Xiaohua4,Chen Xiao‐Dong56,Ng Lai Guan7,Li Xinyu12,Lu Yao12,Cheng Xiaoyue12,Cui Wenguo3ORCID,Sun Yun12

Affiliation:

1. Department of Reproductive Medicine, Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200135 P. R. China

2. Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics Shanghai 200135 P. R. China

3. Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. China

4. Hangzhou Phil Stone Biotech Co., Ltd. Hangzhou Zhejiang 311215 P. R. China

5. Department of Comprehensive Dentistry University of Texas Health Science Center at San Antonio San Antonio TX 78229 USA

6. Research Service South Texas Veterans Health Care System Audie Murphy VA Medical Center San Antonio TX 78229 USA

7. Shanghai Immune Therapy Institute Shanghai Jiao Tong University School of Medicine affiliated Renji Hospital Shanghai 200127 P. R. China

Abstract

AbstractThe prevalence of infertility caused by endometrial defects is steadily increasing, posing a significant challenge to women's reproductive health. In this study, injectable “homing‐like” bioactive decellularized extracellular matrix short‐fibers (DEFs) of porcine skin origin are innovatively designed for endometrial and fertility restoration. The DEFs can effectively bind to endometrial cells through noncovalent dipole interactions and release bioactive growth factors in situ. In vitro, the DEFs effectively attracted endometrial cells through the “homing‐like” effect, enabling cell adhesion, spreading, and proliferation on their surface. Furthermore, the DEFs effectively facilitated the proliferation and angiogenesis of human primary endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs), and inhibited fibrosis of pretreated HESCs. In vivo, the DEFs significantly accelerated endometrial restoration, angiogenesis, and receptivity. Notably, the deposition of endometrial collagen decreased from 41.19 ± 2.16% to 14.15 ± 1.70% with DEFs treatment. Most importantly, in endometrium‐injured rats, the use of DEFs increased the live birth rate from 30% to an impressive 90%, and the number and development of live births close to normal rats. The injectable “homing‐like” bioactive DEFs system can achieve efficient live births and intrauterine injection of DEFs provides a new promising clinical strategy for endometrial factor infertility.

Funder

National Natural Science Foundation of China

National Key Research and Development Program of China

Publisher

Wiley

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