Semiconducting polymer nanoparticles laden with platelet-rich plasma for endometrium regeneration via regulating macrophage M1/M2 type polarization

Abstract

Thin endometrium is linked to recurrent miscarriage and infertility. Reliable clinical strategies for endometrium regeneration are lacking. Human platelet-rich plasma (PRP), especially derived from umbilical cord blood, shows promising regenerative capabilities. Here, we designed a construct of the human umbilical cord blood-derived PRP and the as-synthesized semiconducting polymer nanoparticles (SPNs) for promoting endometrial regeneration and fertility restoration following in situ microinjection in a rat model of endometrial damage. The mechanistic basis for the regenerative benefits of these PRP-SPNs was also assessed, with a particular focus on the regulation of macrophage activity. In vitro, PRP-SPNs treatment was sufficient to enhance the proliferation of human endometrial stromal cells. In vivo, PRP-SPNs administration induced robust endometrial proliferation, re-epithelialization, and angiogenic activity while inhibiting localized fibrosis. Critically, the regenerated endometrium exhibited enhanced receptivity such that it was conducive to higher rates of implantation and fetal development. At the cellular level, PRP-SPNs were found to promote the polarization of CD163+ M2 macrophages while coordinating the induction of more effective anti-inflammatory responses in vivo and in vitro. Together, these results suggest that PRP-SPNs represent a safe, effective, noninvasive approach that can be conveniently implemented to remediate thin endometrium and restore fertility for patients in need.