Adhesive complex coacervate inspired by the sandcastle worm as a sealant for fetoscopic defects.

摘要

Inspired by the Sandcastle Worm, biomimetic of the water-borne adhesive was developed by complex coacervation of the synthetic copolyelectrolytes, mimicking the chemistries of the worm glue. The developed underwater adhesive was designed for sealing fetal membranes after fetoscopic surgery in twin-to-twin transfusion syndrome (TTTS) and sealing neural tissue of a fetus in aminiotic sac for spina bifida condition.;Complex coacervate with increased bond strength was created by entrapping polyethylene glycol diacrylate (PEG-dA) monomer within the cross-linked coacervate network. Maximum shear bond strength of ~ 1.2 MPa on aluminum substrates was reached. The monomer-filled coacervate had complex flow behavior, thickening at low shear rates and then thinning suddenly with a 16-fold drop in viscosity at shear rates near 6 s-1. The microscale structure of the complex coacervates resembled a three-dimensional porous network of interconnected tubules. This complex coacervate adhesive was used in vitro studies to mimic the uterine wall-fetal membrane interface using a water column with one end and sealed with human fetal membranes and poultry breast, and a defect was created with an 11 French trocar. The coacervate adhesive in conjunction with the multiphase adhesive was used to seal the defect. The sealant withstood an additional traction of 12 g for 30-60 minutes and turbulence of the water column without leakage of fluid or slippage. The adhesive is nontoxic when in direct contact with human fetal membranes in an organ culture setting.;A stable complex coacervate adhesive for long-term use in TTTS and spina bifida application was developed by methacrylating the copolyelectrolytes. The methacrylated coacervate was crosslinked chemically for TTTS and by photopolymerization for spina bifida. Tunable mechanical properties of the adhesive were achieved by varying the methacrylation of the polymers. Varying the amine to phosphate (A/P) ratio in the coacervate formation generated a range of viscosities. The chemically cured complex coacervate, with sodium (meta) periodate crosslinker, was tested in pig animal studies, showing promising results. The adhesive adhered to the fetal membrane tissue, with maximum strength of 473 +/- 82 KPa on aluminum substrates. The elastic modulus increased with increasing methacrylation on both the polyphosphate and polyamine within the coacervate. Photopolymerized complex coacervate adhesive was photocured using Eosin-Y and treiethanolamine photoinitiators, using a green laser diode. Soft substrate bond strength increased with increasing PEG-dA concentration to a maximum of ~90 kPa. The crosslinked complex coacervate adhesives with PEG networks swelled less than 5% over 30 days in physiological conditions. The sterile glue was nontoxic, deliverable through a fine cannula, and stable over a long time period. Preliminary animal studies show a novel innovative method to seal fetal membrane defects in humans, in utero.