Amnion‐Analogous Medical Device for Fetal Membrane Healing: A Preclinical Long‐Term Study

Abstract

Although recent invasive fetal surgeries have improved fetal outcomes, fetal membrane rupture remains a major complication, leading to premature delivery, thus undermining the complete benefits of such procedures. A biocompatible amnion-analogous medical device (AMED) consisting of polycaprolactone framework and decellularized amniotic membrane (dAM)-derived hydrogel for restoration of amniotic membrane defect is developed using 3D printing technology. Its efficacy on healing iatrogenic fetal membrane defects in vitro is evaluated, showing that the dAM gel contains migratory and proliferative properties. The fetoscope feasibility of the developed AMED is assessed using a pregnant swine model. All animals had successfully recovered from anesthesia and the fetoscopic procedure and maintained a healthy condition until the end of the pregnancy. AMED exhibits superior surgical handling characteristics and is easy to manufacture, nonimmunogenic, biocompatible, and suitable for storage and transport for off-the-shelf use; hence, it can be used in successfully sealing defect sites, thus improving the preservation of the amniotic fluid, which in turn improves fetal survival and development.

Development of Injectable Amniotic Membrane Matrix for Postmyocardial Infarction Tissue Repair

“…The collagen content of the decellularized hAM matrix was measured by a hydroxyproline assay kit (Cell Biolabs Inc) by following the vendor's protocol as previously described. [30] Briefly, hAM powder was hydrolyzed by 12N hydrochloric acid for 3 hours at 120º C to free hydroxyproline. The acid-hydrolyzed samples were further dried under vacuum evaporation at 80ºC for 40 minutes.…”

Biomaterial-based treatments for the prevention of preterm birth after iatrogenic rupture of the fetal membranes

“…Recently, an amnion-analogous device (AMED) for the positioning of a 3D-printed medical device filled with a DAM-based solution in swine was developed. 106 The use of the device improved fetal survival rate and AF presence rates when compared to non-treated controls, but it was still lower than for intact FMs.…”

“…Investigations with larger animals have included trials in swine, sheep and rhesus monkey. 106–109 Although they have longer gestational periods and are bigger in size, swine should be discarded in FM repair studies because the spontaneous healing of their FMs has been observed. 108 Sheep, on the other hand, would be more adequate models since they also have long gestational periods and a size that is almost directly translatable to humans.…”

Supramolecular Adhesive Hydrogels for Tissue Engineering Applications

“…Although there have been significant advances in fetal diagnosis, the FMs are inevitably breached during fetal surgeries and therapies. 365 Previous studies have shown that the destruction of FMs cannot be healed entirely due to their largely avascular physiological state. 366,367 Therefore, the FM rupture makes fetal surgery extremely dangerous, and it is related to premature preterm rupture of membranes (PPROM) in some cases, which can lead to fetal death.…”