Repairing Fetal Membranes with a Self-adhesive Ultrathin Polymeric Film: Evaluation in Mid-gestational Rabbit Model

Abstract

Preterm premature rupture of membranes (PPROM) causes 40% of all preterm births, affecting 150,000 women each year in the United States. Prenatal diagnostic procedures and surgical interventions increase incidence of adverse events, leading to iatrogenic membrane rupture after a fetoscopic procedure in 45% of cases. We propose an ultrathin, self-adherent, poly-L-lactic acid patch ("nanofilm") as a reparative wound closure after endoscopic/fetoscopic procedures. These nanofilms are compatible with application in wet conditions and with minimally invasive instrumentation.Ex vivo studies to evaluate the nanofilm were conducted using human chorion-amnion (CA) membranes. A custom-built inflation device was used for mechanical characterization of CA membranes and for assessment of nanofilm adhesion and sealing of membrane defects up to 3 mm in size. These ex vivo tests demonstrated the ability of the nanofilm to seal human CA defects ranging in size from 1 to 3 mm in diameter. In vivo survival studies were conducted in 25 mid-gestational rabbits, defects were created by perforating the uterus and the CA membranes and subsequently using the nanofilm to seal these wounds. These in vivo studies confirmed the successful sealing of defects smaller than 3 mm observed ex vivo.Histological analysis of whole harvested uteri 7 days after surgery showed intact uterine walls in 59% of the nanofilm repaired fetuses, along with increased uterine size and intrauterine development in 63% of the cases. In summary, we have developed an ultrathin, self-adhesive nanofilm for repair of uterine membrane defects.

Polymeric Microporous Nanofilms as Smart Platforms for <italic>in Vitro</italic> Assessment of Nanoparticle Translocation and Caco-2 Cell Culture

“…The application of nanofilms during surgical and medical procedures may be facilitated by using thick supporting layers coupled with the membranes. Supporting sacrificial layers would allow manipulation and positioning of the nanofilm in the desired site, before dissolving in physiological media [23,24,39]. Finally, for some applications, nanofilms have been designed to be built directly onto the target device or tissue [36,40].…”

“…3A. Previous studies have demonstrated that the thickness of ultra-thin polymeric films can be varied by simply regulating the spinning speed [22][23][24][25][26]. Fig.…”

“…Poly(L-lactic acid) (PLLA) has been demonstrated to be particularly suitable for the development of robust, yet highly flexible free-standing nanomembranes featured by optical transparency, low-cost and ease of fabrication (based on spin-assisted deposition) [22]. The potential of PLLA nanofilms for a series of biomedical applications has been recently highlighted, ranging from surgical sealing [23,24] to regenerative medicine [25] and drug delivery [26]. However, microporous PLLA nanofilms and their application in lab-on-chip systems have not been reported.…”

Ultrathin Polymer Membranes with Patterned, Micrometric Pores for Organs-on-Chips

“…39,40 In the present work, arrays of freestanding polyvinyl alcohol (PVA) nanoneedles (or PVA replicas) were prepared using the water/alcohol-based PVA mold release agent Partall® Film #10 (Rexco). In particular, each fused silica mold containing an array of surface pores was coated with a thin layer of Partall® Film #10 using a foam paintbrush.…”

What is the Future of Intrauterine Surgery?

“…Research has revolved around preventing such complications as amniotic fluid leakage, preterm premature rupture of membranes and preterm labor. [4][5][6][7][8] Iatrogenic preterm premature rupture of the membranes (PPROM) is a significant factor contributing to perinatal outcome. Even a small diameter puncture, due to disruption of the fetal membranes increases the risk fo PPROM.…”