# Co-delivery of endometrial mesenchymal stem cells and macrophages by an electrospun patch promotes angiogenesis during endometrial injury repair via VEGF related signalling

## TL;DR

A new patch combining stem cells and immune cells promotes blood vessel growth to repair uterine damage, which could improve infertility treatment.

## Contribution

A co-delivery system of endometrial stem cells and macrophages on an electrospun patch enhances angiogenesis via VEGF signaling for endometrial repair.

## Key findings

- The co-delivery system increased endometrium thickness and gland numbers in a rat model of endometrial injury.
- The system enhanced CD31 gene and protein expression, indicating improved angiogenesis.
- Elevated VEGF production was identified as a key factor in the observed angiogenesis.

## Abstract

Intrauterine adhesion (IUA) is a common gynecological disease that contributes to infertility. Decreased endometrial angiogenesis and uterine ischemia are major therapeutic challenges for IUA and cannot be addressed by current treatment strategies. Human endometrial mesenchymal stem cells (H-EMSCs) and macrophages (mø) are both important cell types that reside within the endometrial tissue and participate in its repair and regeneration. However, how to harness the endometrial tissue repair potential of H-EMSCs and mø simultaneously in a co-delivery system and whether there are significant biochemical cross-talks between the two cell types so that they can regulate each other to specifically boost endometrial tissue angiogenesis remains to be explored.

This study developed a H-EMSCs-mø co-delivery system using an electrospun polycaprolactone-hyaluronic acid (PCL-HA) membrane and established a rat endometrial damage model. The effects of the co-delivery system on endometrial tissue repair (endometrium thickness, endometrial glands number) and angiogenesis were investigated. The mechanisms underlying the enhanced endometrial tissue angiogenesis of the H-EMSCs-mø co-delivery system were also delineated. All data were analyzed using analysis of variance with Tukey’s test for pair-wise comparisons or an independent samples t-test where appropriate.

In this study, it was found that a H-EMSCs and mø co-delivery system developed with a PCL-HA electrospun membrane carrier (PCL-HA/H-E/mø) significantly increased the endometrium thickness and restored the number of endometrial glands at day 7 and 14 in the endometrial damage model vs. the NR (normal repair) and PCL-HA alone groups. Further, PCL-HA/H-E/mø enhanced more CD31 gene and protein expression, indicating great potential for angiogenesis to occur at day 7 and 14 post-implantation, when compared with PCL-HA/H-E, NR or PCL-HA alone. It was also proved to demonstrated that elevated VEGF production was one of the potential factors that contributed to the enhanced angiogenesis of the co-delivery patch system.

This study provided significant insights into the use of co-delivered H-EMSCs and mø, on a PCL-HA hybrid electrospun membrane, for effectively inducing endometrial angiogenesis and repair to enhance IUA treatment outcomes.

The online version contains supplementary material available at 10.1186/s13287-026-04929-2.

This study developed a H-EMSCs and mø co-delivery system (PCL-HA/H-E/mø)

PCL-HA/H-E/mø increased endometrium thickness and restored glands number

PCL-HA/H-E/mø enhanced CD31 gene and protein expression showing more angiogenesis

Elevated VEGF production could have caused angiogenesis in PCL-HA/H-E/mø system

PCL-HA/H-E/mø hybrid system induced endometrial angiogenesis and could treat IUAs

The online version contains supplementary material available at 10.1186/s13287-026-04929-2.