Potential of Estradiol-Functionalized Polyisocyanide Hydrogels for Stimulating Tissue Regeneration of the Pelvic Floor

The high reoperation rate in pelvic organ prolapse (POP) surgery is probably due to impaired wound healing, and therefore, novel strategies that promote tissue regeneration are urgently needed. Estrogen therapy shows beneficial effects for vaginal wound healing: it reduces the inflammatory response and improves vaginal tissue strength and quality. Earlier, scaffolds that release the most potent estrogen, & beta;-estradiol (E2) have been described. This work describes the results of conjugating E2 covalently to the synthetic, but highly mimetic, polyisocyanide hydrogel (PIC-E2). As adipose-derived stem cells (ASCs) possess regenerative capabilities, the combination of PIC-E2 and ASCs may have a synergistic effect on pelvic floor tissue regeneration. The results show that the PIC-E2 bioactivity is not hampered upon covalent E2 conjugation and upregulates various extracellular matrix (ECM) genes in ASCs. Moreover, PIC-E2 exerts similar effects regarding ECM metabolism compared to other E2-releasing biomaterials, but at much lower doses, which is economically and therapeutically favorable. Based on these in vitro findings, the combination of the PIC-E2 hydrogel and ASCs may have the potential to stimulate tissue regeneration in vivo, and therefore, feasibly improve the surgical outcomes for POP in the future. & beta;-Estradiol has the potential to stimulate pelvic floor tissue regeneration. Its covalent conjugation to the polyisocyanide-based hydrogel does not hamper its bioactivity and upregulates extracellular matrix genes in adipose-derived stem cells. The results suggest that the combination of the hormone-modified gel with the stem cells holds the potential to stimulate regeneration of the pelvic floor tissues.image

Automated summary

This study investigated a method of covalently conjugating β-estradiol to a polyisocyanide-based hydrogel and found that it could upregulate extracellular matrix genes in adipose-derived stem cells. Additionally, compared to other E2-releasing biomaterials, this method required a lower dosage and may potentially improve the outcomes of pelvic organ prolapse surgery in the future.