Vol. 24, Issue 1: Fall 2016
A comparative investigation of mussel-mimetic sealants for fetal membrane repair
Many infants are born with treatable issues that go on to negatively impact them for the remainder of their lives. In many cases, doctors have the tools and knowledge to treat the fetus, but only after doctors are able to reach them inside the womb. Here lies the problem: the protective membrane surrounding the fetus is fragile and easily broken, putting the fetus at risk of death upon rupture. However, researchers are attempting to make a strong, mussel-derived sealant for the membrane, an innovation that could immensely expand the realm of possibilities for life-saving fetal surgery.
Fetal membrane surgery can be performed to treat fetal complications, including congenital diaphragmatic hernia and twin-to-twin transfusion syndrome. Though this surgery is necessary, it poses risks to the fetuses as their fetal membrane is very weak. The largest risk of fetal surgery is iatrogenic preterm premature rupture of fetal membranes (iPPROM), during which the membrane ruptures unexpectedly anytime before 34 weeks of pregnancy. iPPROM can be caused by defects in the membrane and the inability of the tissue to heal correctly. The risk of iPPROM is very high, severely limiting the range of procedures that can be performed on the fetuses.
Researchers are attempting to create a sealant to repair damaged fetal membranes when iPPROM occurs. Current potential sealants include platelet-rich plasma, fibrin glue, and collagen plugs. However, creating sealants is very difficult, as sealants must be able to work in a wet environment, resist high levels of pressure, and logistically adhere onto the fetus for long periods of time. None of the options so far are able to do this extremely effectively.
Martin Ehrbar of the University of California, Berkeley is attempting to design a fetal membrane sealant from mussels. Two types of sealants are being tested: cT, or catechol-modified Tetronic and cPEG. cPEG, a polyethylene glycol, has strong adhesive and cohesive properties, but cT, a PPO-PEO, or polypropylene oxide-poly(ethylene oxide)) block copolymer, has shown to be more malleable and resilient, so the researchers hypothesized that cT has more promising prospects as a membrane sealant.
Mussels were chosen due to their high concentrations of a rare non-proteinogenic amino acid called cPEG, a polyethylene glycol that, in previous rabbit models, allowed the sealant to have effective adhesion and cohesion with the membrane. These properties also allowed the sealant to remain intact under high pressures, similar to the type of pressures the sealant would experience during the mother’s contractions.
In a recent study, researchers gathered samples from eight human fetal membranes from infants delivered via elective Cesarean section from healthy mothers. The membranes were punctured with trocars to mimic membrane defects of various sizes and shapes. Next, mussel-mimetic sealant was applied to each membrane. Membranes were then inflated to the point of rupture via one of three techniques, each differing in time and pressure. They examined the pressure at which the membranes ruptured.
Researchers determined that both membranes withstood pressures greater than the average pressures of contractions in the womb. Only after repeated bouts of pressure does cPEG finally break. cT does unattach from the membrane, but it does not break.
The quest continues to find the perfect sealant that will fulfill three main functions: accommodate the membrane deformation without breaking or detaching, reduce stress concentrations, and adhere to a substrate undergoing a significant remodeling process and changes in stiffness. However, the results from these aforementioned experiment are promising: the sealants were tested under pressures much greater than normal uterine pressures. Much research still needs to be done, but this is a breakthrough in the realm of fetal membrane repair.
About the Author
Quincy Seigel is a third-year intended Public Health major at UC Berkeley. In the future, she hopes to attend medical school to become a dermatologist or burn surgeon.