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

Abstract

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 have been described that release β‐estradiol (E2), which is the most potent estrogen. 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.This article is protected by copyright. All rights reserved

Conductive Polyisocyanide Hydrogels Inhibit Fibrosis and Promote Myogenesis

“… 21 , 22 In these applications, PIC is biofunctionalized with the commonly used cell-adhesive peptide Gly-Arg-Gly-Asp-Ser (RGD) that allows cell–matrix interactions via integrin binding, but other biological cues can be inserted similarly. 23 These and many other studies demonstrate the capacity of PIC gels to combine a high degree of tunability and similar mechanical properties as native tissue, which makes them particularly suitable for in vitro studies and different tissue engineering purposes.…”

“…We use hydrogels based on polyisocyanides (PICs), which form a relatively new class of tunable soft materials . By tailoring the molecular weight and polymer concentration, the mechanical properties and network architecture can be controlled for native tissue. , As a result, the material has been successfully applied as a matrix material for 3D in vitro studies to study single cell , and organoid behavior. , Additional in vivo experiments indicate that PIC hydrogels are nontoxic and biocompatible. , In these applications, PIC is biofunctionalized with the commonly used cell-adhesive peptide Gly-Arg-Gly-Asp-Ser (RGD) that allows cell–matrix interactions via integrin binding, but other biological cues can be inserted similarly . These and many other studies demonstrate the capacity of PIC gels to combine a high degree of tunability and similar mechanical properties as native tissue, which makes them particularly suitable for in vitro studies and different tissue engineering purposes.…”