Growth factor-loaded ovarian extracellular matrix hydrogels promote in vivo ovarian niche regeneration and enhance fertility in premature ovarian insufficiency preclinical models

• DOI: 10.1016/j.actbio.2024.07.056
• Publication Date: 2024-08-05T18:18:28Z
• Authors: Emilio Francés-He...; Clara Bueno-Ferna...; Adolfo Rodríguez-...; María Gómez-Álvarez; Amparo Faus; Alexandra Soto-Prado; Anna Buigues; Sonia Herraiz; Antonio Pellicer; Irene Cervelló
• Keywords: Premature ovarian insufficiency; Ovarian Cortex; Premature ovarian failure

Premature ovarian insufficiency (POI) means menopause before 40 years of age affecting about 1 % women. Approaches based on cell therapy and the paracrine effects stem cells or bioproducts such as platelet-rich plasma have been proposed, but concerns remain undesired systemic effects, well need to optimize delivery methods through bioengineering methods. This study explores efficacy decellularized bovine cortex extracellular matrix (OvaECM) hydrogels alone a growth factor (GF) carrier (OvaECM+GF) in chemotherapy-induced POI murine model. In vitro assays showed gradual release GF from OvaECM sustained for two weeks. Chemotherapy drastically reduced follicle numbers, OvaECM+GF treatment restored pre-antral development. Moreover, this notably regenerated microenvironment by increasing proliferation microvessel density while reducing apoptosis fibrosis. Whole-ovary RNA sequencing gene set enrichment analysis revealed an upregulation regeneration-related genes downregulation apoptotic pathways. The also yielded significantly better outcomes following stimulation fertilization. After consecutive crossbreeding cycles, OvaECM+GF-treated mice normal reproductive function. research showcases biocompatibility reverse mice, setting foundation explore innovative bioengineering-based therapies. affects women worldwide, causing early old. Current treatments alleviate symptoms do not restore approach using deliver factors into niche POI. kinetic demonstrated factors. POI-induced mouse model, intraovarian injections hydrogel encapsulating development, increased proliferation, fibrosis, improved response fertilization outcomes. Long-term benefits included larger litter sizes. technique shows promise regenerating environment improving