Adaptive MSC@ECM/PRP Matrix Sustains Transplanted Stem Cells and Restores Endometrial Regeneration

Stem cell-based therapy holds promise for endometrial regeneration but suffers from rapid cell loss in the oxidative and cytokine-deficient uterine niche. We developed a biomimetic decellularized extracellular matrix integrated with platelet-rich plasma (ECM/PRP) that serves as a bioactive cytokine reservoir designed to construct a supportive local microenvironment capable of retaining cytokines and maintaining transplanted cell viability. The ECM binds PRP-derived cytokines, stabilizing their bioactivity and converting burst release into sustained signaling. Adhered human umbilical cord mesenchymal stem cells (HUC-MSCs) respond to these anchored cues, with changes in mitochondrial electron transport activity correlating with enhanced cellular antioxidant capacity. This ECM/PRP composite improves HUC-MSC survival, alleviating intracellular ROS, sustain their paracrine secretion under the IUA pathological microenvironment, and elevate the number of surviving transplanted HUC-MSCs in vivo. In a murine intrauterine adhesion (IUA) model, MSC@ECM/PRP enhanced endometrial proliferation and microvessel density while reducing collagen deposition. These coordinated changes facilitate reconstruction of physiological endometrial structure and produce a marked improvement in fertility relative to the untreated IUA group. Collectively, the adaptive MSC@ECM/PRP scaffold protects transplanted HUC-MSCs against oxidative stress in the IUA microenvironment, facilitates endometrial structural repair and angiogenesis, suppresses excessive fibrosis, and achieves satisfactory therapeutic and fertility-restoring effects in IUA.