Bioinspired Adhesives for Fetal Membrane Presealing

Fetal surgery can improve outcomes for severely affected fetuses, but carries a substantial risk of preterm birth. In order to perform surgery on the fetus, surgeons must breach the fetal membranes, a pair of fragile tissues that are susceptible to post-surgical rupture. Here, we sought to develop adhesives to seal this non-healing tissue, decreasing the overall risk of fetal surgery and making it an option for more families. The central challenge of fetal membrane sealing is achieving robust adhesion in a wet environment. In designing our adhesives, we took inspiration from marine mussels. Mussels secrete adhesive plaques rich in the amino acid 3,4- dihydroxyphenylalanine (DOPA) to adhere to diverse underwater surfaces, and we incorporated similar DOPA chemistry into our adhesives. We designed both injectable hydrogel adhesives and supramolecular adhesive patches and measured their adhesive strength and cytocompatibility. The adhesive hydrogels were also studied in a novel rabbit model of fetal membrane presealing. Membrane presealing is a proposed surgical approach in which the delicate fetal membranes are sealed prior to surgical puncture, stabilizing them, reducing the risk of membrane leakage and rupture, and decreasing the overall risk of fetal surgery. In this animal model, our mussel-inspired formulation appeared to be fetotoxic, but with an alternative adhesive, we found that fetal membrane presealing appeared facile and safe for mothers and fetuses. I also sought to understand how our materials interact with human fetal membrane tissues in vitro, and developed protocols to culture these tissues and their cells ex vivo. We used these cultures to analyze the cytocompatibility of our adhesives with clinically relevant primary cells and tissues, and took the initial steps to investigate the potential for a small molecule regenerative drug candidate (dihydrophenonthrolin-4-one-3-carboxylic acid, DPCA) to regenerate human fetal membranes in vitro. In this work, we created novel, mussel-inspired adhesive hydrogels and patches; established the feasibility of fetal membrane presealing in vivo; and developed human fetal membranes as an ex vivo tool for biomaterial-tissue compatibility evaluation