Disrupted uterine scar healing may drive placenta accreta spectrum development

Placenta accreta spectrum (PAS), once considered a rare obstetric complication, now affects an estimated 14,000 pregnancies each year and remains a leading cause of severe maternal morbidity and mortality due to hemorrhage and the frequent need for hysterectomy. Although prior cesarean delivery is a well-established risk factor, the biological mechanisms underlying abnormal placental adherence have remained incompletely understood.¹

New research led by investigators at UCLA Health suggests that the key driver of PAS may lie not in aberrant placental behavior, but in how uterine scars heal after prior surgery. The findings, published in the American Journal of Obstetrics and Gynecology, indicate that disorganized collagen architecture and persistent inflammation at cesarean scar sites create a permissive environment for abnormal placental attachment.^1,2

“Our findings show that the main problem in placenta accreta isn’t the placenta growing abnormally – it’s how uterine scarring changes the structure and organization of collagen in the uterus to increase delivery risks,” said Yalda Afshar, MD, associate professor of obstetrics and gynecology in the division of maternal fetal medicine at the David Geffen School of Medicine at UCLA, co-director of the UCLA Health Accreta Care Program and corresponding author of the study.

Examining the uterine scar–placenta interface

To investigate the role of uterine scar remodeling in PAS, researchers used a multimodel approach that included human surgical specimens, a mouse model of uterine injury, and a laboratory-based “accreta-in-a-dish” system. Human tissue samples were obtained from 13 patients with PAS and 10 control patients who had risk factors such as prior cesarean delivery but no evidence of PAS.

Using advanced, label-free three-dimensional imaging techniques, including second harmonic generation and fluorescence lifetime imaging microscopy, investigators examined collagen structure at sites of placental adherence and nonadherence. In PAS samples, collagen fibers at prior scar sites were irregular, tangled, and poorly aligned, with loss of the normal boundary between decidua and placenta. In contrast, control samples demonstrated organized collagen architecture and preserved separation between uterine and placental tissues.

These findings challenge the traditional assumption that PAS primarily results from excessive trophoblast invasion. Instead, the study suggests that abnormal extracellular matrix remodeling at uterine scars undermines the structural integrity of the decidual-placental interface, facilitating abnormal adherence.

Inflammation and impaired scar remodeling

Further analyses showed that persistent inflammation plays a central role in this process. Investigators identified increased macrophage activity at PAS adherence sites, which interfered with normal scar remodeling. In vitro experiments demonstrated that inflammatory conditions weakened scar resistance, while collagen-rich environments improved wound healing and structural strength.

In the laboratory “accreta-in-a-dish” model, decidualized human uterine fibroblasts were used to simulate scar formation. Collagen-coated surfaces promoted faster wound closure and increased resistance to stress, whereas inflammatory signaling disrupted healing and reduced scar integrity. When trophoblast-like cells were introduced, they preferentially avoided areas rich in organized extracellular matrix and migrated toward regions with collagen depletion, mimicking patterns observed in PAS.

“Not all scars heal the same way,” Afshar said. “This work helps explain why some patients with prior cesarean develop placenta accreta while other do not and points to new ways we might identify risk earlier, before pregnancy or early in gestation.”

Implications for risk assessment and prevention

Taken together, the findings suggest that PAS is a disorder of impaired uterine wound healing rather than unregulated placental invasion. By identifying disrupted collagen architecture and inflammatory signaling as defining features of PAS pathology, the study highlights potential opportunities for improved risk stratification and prevention.

Although the research does not yet translate into immediate clinical interventions, it raises the possibility that evaluating uterine scar quality—rather than relying solely on obstetric history—could improve early identification of patients at risk. In the longer term, therapeutic strategies aimed at optimizing uterine healing after cesarean delivery or modulating inflammation may reduce PAS incidence.

The authors note several limitations, including the relatively small number of human specimens and the focus on specific collagen subtypes. Future studies are needed to explore additional aspects of extracellular matrix remodeling, validate biomarkers of abnormal scar healing, and determine whether these mechanistic insights can be applied to clinical screening or preventive care.

Nonetheless, the study provides a clearer biological framework for understanding why PAS develops in some patients with prior cesarean delivery but not others. By shifting attention from placental behavior to uterine scar integrity, the findings represent an important step toward addressing a growing and life-threatening obstetric condition.

References

1. University of California - Los Angeles Health Sciences. UCLA study links scar healing to dangerous placenta condition. January 2, 2026. Accessed January 5, 2025. https://www.eurekalert.org/news-releases/1111354
2. Kashani Ligumsky L, Jeong A, Martinez G, et al. Placenta accreta spectrum: disrupted collagen architecture at a previous scar is a defining characteristic of placental adherence. American Journal of Obstetrics and Gynecology. 2026;233(6):S645-S661.e1. doi:https://doi.org/10.1016/j.ajog.2025.08.094