Potential sealing and repair of human FM defects after trauma with peptide amphiphiles and Cx43 antisense.

David W Barrett,David L Becker,Christopher Thrasivoulou,Alvaro Mata,Babatunde O Okesola,Anna L David,Jan A Deprest,Tina T Chowdhury,Eleni Costa

doi:10.1002/pd.5826

Abstract

We examined whether peptide amphiphiles functionalised with adhesive, migratory or regenerative sequences could be combined with amniotic fluid (AF) to form plugs that repair fetal membrane (FM) defects after trauma and co-culture with connexin 43 (Cx43) antisense. We assessed interactions between peptide amphiphiles and AF and examined the plugs in FM defects after trauma and co-culture with the Cx43antisense. Confocal microscopy confirmed directed self-assembly of peptide amphiphiles with AF to form a plug within minutes, with good mechanical properties. SEM of the plug revealed a multi-layered, nanofibrous network that sealed the FM defect after trauma. Co-culture of the FM defect with Cx43 antisense and plug increased collagen levels but reduced GAG. Culture of the FM defect with peptide amphiphiles incorporating regenerative sequences for 5 days, increased F-actin and nuclear cell contraction, migration and polarization of collagen fibers across the FM defect when compared to control specimens with minimal repair. Whilst the nanoarchitecture revealed promising conditions to seal iatrogenic FM defects, the peptide amphiphiles need to be designed to maximize repair mechanisms and promote structural compliance with high mechanical tolerance that maintains tissue remodeling with Cx43 antisense for future treatment.

Highlights

Strategies to seal and repair defects in the fetal membrane (FM) after fetal surgery are important to prevent iatrogenic preterm prelabour rupture of the membranes (PPROM)
Even after fetoscopy which results in trauma, the membranes do not heal and a visible defect is left in the FM that is prone to amniotic fluid (AF) leakage and subsequent iatrogenic PPROM.[1]
We showed that functionalizing the peptide amphiphiles with bioactive sequences to promote cell adhesion, migration and regeneration or culturing with connexin 43 (Cx43) antisense improves sealing and the repair of defects in the fetal membrane

Summary

Introduction

Strategies to seal and repair defects in the fetal membrane (FM) after fetal surgery are important to prevent iatrogenic preterm prelabour rupture of the membranes (PPROM). Membranes separate in up to 30% of patients commonly leading to PPROM and preterm birth.[1] Even after fetoscopy which results in trauma, the membranes do not heal and a visible defect is left in the FM that is prone to AF leakage and subsequent iatrogenic PPROM.[1] The subsequent preterm birth compromises the outcome of treatment, reducing the clinical effectiveness of fetal surgery.[2] Currently, there are no clinical solutions to improve healing of the FM after trauma or rupture. Several novel sealing techniques are aiming to restore a physical barrier against infection encouraging re-accumulation of AF. The approaches either (a) seal the FM defect with natural, synthetic or injectable materials such as plugs, films, sponge, patches, sealants and Prenatal Diagnosis. The approaches either (a) seal the FM defect with natural, synthetic or injectable materials such as plugs, films, sponge, patches, sealants and Prenatal Diagnosis. 2020;1–11

Methods

Findings

Discussion

Conclusion