Standardizing decellularization protocols for optimized uterine tissue bioengineering

Bioengineering is applied in different areas, including women's infertility management. Among other approaches, decellularized tissues are being used to treat uterine disorders causing infertility. Biomaterials made from decellularized tissue consist of tissue-specific extracellular matrix and, as acellular scaffolds, are thought to be immune inert. Hence, they are good grafting candidates to replace and regenerate excised damaged uterine tissue to cure infertility. However, decellularization approaches differ among species and research groups, posing challenges for comparison and standardization. The diversity in data reporting and studied properties of the resulting decellularized scaffold make it even more difficult, especially when the ultimate goal is clinical translation. Thus, this review aims to critically assess whole uterus decellularization studies, extracting and comparing their main results and conclusions. After carefully evaluating the reviewed studies, we noticed that the vast majority base the uterus decellularization success and resulting scaffold efficacy on the DNA removal efficacy, while other crucial aspects, including the extracellular matrix integrity or immunogenicity, are underestimated. Thus, this review further proposes practical points for what should be considered and how results can be reported in studies involving whole uterus decellularization to facilitate comparison between studies and translational progress. Decellularized tissues have emerged as a promising therapeutic approach to treat uterine disorders, as the resulting acellular extracellular matrix (ECM) is a good grafting candidate to replace and regenerate excised damaged uterine tissue, thereby addressing infertility. However, decellularization protocols differ among species and research groups (e.g., choice of decellularization agents), complicating efforts to compare and standardize procedures. There is also diversity in data reporting and studied properties of the resulting decellularized scaffolds. A thorough revision of the available literature suggests that beyond successful cell removal, the scaffolds' ECM integrity, biocompatibility, and immunogenicity should also be addressed. • Decellularized scaffolds need to maintain the extracellular matrix integrity. • A balance between cell removal and extracellular matrix preservation is critical. • The scaffold's biocompatibility and immunogenicity should always be considered.