Regenerative Potential of Platelet-Rich Plasma-Loaded Scaffolds in Endometrial Damage: A Meta-Analysis

Abstract

This systematic review and meta-analysis evaluated the efficacy of platelet-rich plasma (PRP)-loaded scaffolds for endometrial regeneration in preclinical in vivo models. Endometrial damage, manifesting as endometrial thinning or adhesion formation within the uterine cavity, is a major cause of infertility. While PRP is a promising regenerative therapy, its short half-life limits its effectiveness. The hypothesis was that combining PRP with a hydrogel-based scaffold would provide sustained growth factor release and improve regenerative outcomes compared with monotherapies. The review was conducted per PRISMA guidelines and registered in PROSPERO (CRD420251004274). A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases was carried out through April 2025. Seven studies in rodent models met the inclusion criteria. The meta-analysis demonstrated that PRP/scaffold combinations significantly enhanced key outcomes over untreated controls, including endometrial thickness (standardized mean difference [SMD] = 2.85, p < 0.001), gland density (SMD = 4.11, p < 0.001), angiogenesis (SMD = 6.13, p < 0.001), fibrosis reduction (SMD = −5.21, p < 0.001), and embryo implantation rates (SMD = 4.04, p < 0.001). Injectable hydrogels were particularly effective. Compared with PRP alone, the PRP/hydrogels demonstrated improved performance across the majority of structural and functional parameters, though statistical significance varied, partly attributable to variability in scaffold materials and PRP preparation methods. These results suggest that PRP-loaded scaffolds represent a promising approach for improving both structural and functional endometrial regeneration. The therapeutic success is closely tied to the scaffold’s degradation kinetics and its ability to preserve PRP bioactivity. This evidence supports the further development of standardized, degradable PRP-scaffold systems for clinical translation in treating endometrial infertility.

Impact Statement

This systematic review and meta-analysis represents the first study to quantitatively assess the in vivo regenerative potential of platelet-rich plasma (PRP) incorporated into hydrogel scaffolds for endometrial injury. Across seven preclinical studies, scaffold-assisted delivery enhanced endometrial thickness, glandular density, angiogenesis, and implantation rates, while reducing fibrosis, compared with PRP alone or untreated controls. By prolonging the bioactivity of PRP-derived growth factors and providing structural support, these biomaterial-cell constructs address a key barrier to treating infertility caused by endometrial damage. The findings establish a translational framework for standardized scaffold-PRP systems in reproductive tissue engineering.

Graphical Abstract

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