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Extracellular matrix-derived scaffolds in constructing artificial ovaries for ovarian failure: a systematic
Tong Wu1,2,3, Ke-Cheng Huang1,2,3, Jin-Feng Yan1,2,3,4
1National Clinical Research Center for Obstetrical and Gynecological Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Study Question:
What is the current state-of-the-art methodology assessing decellularized extracellular matrix (dECM)-based artificial ovaries for treating ovarian failure?
Summary Answer:
Preclinical studies have demonstrated that decellularized scaffolds support the growth of ovarian somatic cells and follicles both in vitro and in vivo.
What Is Known Already:
Artificial ovaries are a promising approach for rescuing ovarian function. Decellularization has been applied in bioengineering female reproductive tract tissues. However, decellularization targeting the ovary lacks a comprehensive and in-depth understanding.
Study Design Size Duration:
PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception until 20 October 2022 to systematically review all studies in which artificial ovaries were constructed using decellularized extracellular matrix scaffolds. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol.
Participants/Materials Setting Methods:
Two authors selected studies independently based on the eligibility criteria. Studies were included if decellularized scaffolds, regardless of their species origin, were seeded with ovarian cells or follicles. Review articles and meeting papers were removed from the search results, as were articles without decellularized scaffolds or recellularization or decellularization protocols, or control groups or ovarian cells.
Main Results And The Role Of Chance:
The search returned a total of 754 publications, and 12 papers were eligible for final analysis. The papers were published between 2015 and 2022 and were most frequently reported as coming from Iran. Detailed information on the decellularization procedure, evaluation method, and preclinical study design was extracted. In particular, we concentrated on the type and duration of detergent reagent, DNA and extracellular matrix detection methods, and the main findings on ovarian function. Decellularized tissues derived from humans and experimental animals were reported. Scaffolds loaded with ovarian cells have produced estrogen and progesterone, though with high variability, and have supported the growth of various follicles. Serious complications have not been reported.
Limitations Reasons For Caution:
A meta-analysis could not be performed. Therefore, only data pooling was conducted. Additionally, the quality of some studies was limited mainly due to incomplete description of methods, which impeded specific data extraction and quality analysis. Several studies that used dECM scaffolds were performed or authored by the same research group with a few modifications, which might have biased our evaluation.
Wider Implications Of The Findings:
Overall, the decellularization-based artificial ovary is a promising but experimental choice for substituting insufficient ovaries. A generic and comparable standard should be established for the decellularization protocols, quality implementation, and cytotoxicity controls. Currently, decellularized materials are far from being clinically applicable to artificial ovaries.
Study Funding/Competing Interests:
This study was funded by the National Natural Science Foundation of China (Nos. 82001498 and 81701438). The authors have no conflicts of interest to declare.
Trial Registration Number:
This systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO, ID CRD42022338449).
Insights
Decellularized extracellular matrix (dECM) scaffolds show promise for artificial ovaries, supporting cell and follicle growth in preclinical studies. However, standardized protocols and clinical applicability require further development.
Area of Science:
- Biomaterials Science
- Reproductive Biology
- Tissue Engineering
Background:
- Artificial ovaries represent a promising strategy for restoring ovarian function.
- Decellularization techniques are applied in reproductive tract tissue bioengineering.
- A comprehensive understanding of ovary-specific decellularization is lacking.
Purpose of the Study:
- To systematically review the state-of-the-art methodology for decellularized extracellular matrix (dECM)-based artificial ovaries.
- To assess the current preclinical evidence for dECM scaffolds in treating ovarian failure.
Main Methods:
- A systematic review was conducted following PRISMA guidelines.
- Searches were performed across PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials until October 2022.
- Studies involving decellularized scaffolds seeded with ovarian cells or follicles were included; review articles and papers lacking essential components were excluded.
Main Results:
- Twelve eligible studies published between 2015 and 2022 were analyzed, primarily from Iran.
- Decellularization procedures, evaluation methods, and preclinical designs were detailed, focusing on detergent reagents, DNA/ECM detection, and ovarian function.
- dECM scaffolds derived from human and animal tissues supported ovarian cell growth, hormone production (estrogen, progesterone) with variability, and follicle development, with no reported serious complications.
Conclusions:
- Preclinical studies indicate that decellularized scaffolds can support ovarian cell and follicle growth both in vitro and in vivo.
- Limitations include variability in results, potential bias from single research groups, and incomplete methodological descriptions hindering quality analysis.
- Standardized decellularization protocols, quality control, and cytotoxicity assessments are needed for clinical translation; current dECM materials are not yet clinically applicable for artificial ovaries.

