Tissue adhesives and sealants are ubiquitous in the modern medical and dental clinic, offering a minimally invasive alternative to traditional mechanical closure methods like sutures and staples. These materials allow practitioners to accomplish their clinical goals by providing immediate mechanical support, control bleeding and promote healing of tissues. The term “adhesive” designates a material designed to mechanically bond tissue edges together or a device to a tissue, whereas a “sealant” functions as a barrier to prevent the leakage of air, blood, or other bodily fluids. In reality, most products approved for internal (surgical) use fall into the sealant category because of low strength or poor tissue adhesion to wet tissue. High strength cyanoacrylate (i.e. superglue) is widely approved for external wound closure but is used less for surgical (internal) adhesion due to potential toxicity and slow degradation. Thus, a significant need exists for new and improved surgical sealants and adhesives.
Fetal Membrane Sealants
Dramatic advances in fetal diagnosis have led to a significant increase in indications for which fetal surgical intervention is a viable option. While some prenatally diagnosed conditions can be left untreated or addressed postnatally, others associated with high mortality and morbidity require surgical intervention in utero. A common post-surgical complication of fetal surgery is preterm premature rupture of membranes (PPROM), which occurs in up to 30% of cases, increasing the risk of preterm delivery and neonatal morbidity. The lack of options to effectively repair surgically induced (iatrogenic) membrane defects remains a critical obstacle to improving outcomes following fetal surgery. We are working with clinical collaborators in Switzerland and at UCSF to develop new polymer sealants for fetal surgery.
Reviews
D.W.R. Balkenende, S.M. Winkler, P.B. Messersmith, “Marine-inspired polymers in medical adhesion”, European Polymer Journal, 2019, 116, 134-143. [Link]
S.M. Winkler, M.R. Harrison, P.B. Messersmith, “Biomaterials in Fetal Surgery”, Biomaterials Science 2019, 7, 3092 – 3109. [Link]
We published several studies since 2010, showing good biological tolerance and mechanical adhesion of bioinspired polymer sealants to fetal membranes, both in-vitro and in-vivo. In one study, our mussel-inspired polymer hydrogel sealant was successfully deployed for sealing surgically induced membrane ruptures in pregnant sheep. Most recently, we tested our new alpha-lipoic acid polymer sealant for gestational sac sealing in a timed pregnant murine animal model. The sealant adhered strongly to the tissue, was well tolerated, and reduced amniotic fluid leakage. Importantly, 100% fetal survival was observed in punctured + sealed sacs, compared to 0% survival in unsealed punctured sacs.
Representative Papers
S. Pal, J. Shin, K. DeFrates, M. Arslan, K. Dale, H. Chen, D. Ramirez, P.B. Messersmith, “Recyclable Surgical, Consumer and Industrial Adhesives of Poly(-lipoic acid)”, Science, 385, 829-830 (2024). [Link]
G. Bilic, C. Brubaker, P. B. Messersmith, A. S. Mallik, T. Quinn, E. Done, L. Gucciardo, S. M. Zeisberger, R. Zimmermann, J. Deprest, and A. H. Zisch, “Injectible candidate sealants for fetal membrane repair: Bonding and toxicity in vitro”, American Journal of Obstetrics and Gynecology, 202, 85.e1-9(2010). [Link]
A. Kivelio, P. Dekoninck, M. Perrini, C.E. Brubaker, P.B. Messersmith, E. Mazza, J. Deprest, R. Zimmermann, M. Ehrbar, N. Ochsenbein-Koelble, “Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits”, European Journal of Obstetrics & Gynecology and Reproductive Biology, 2013, 171, 240-245. [Link]
E. Avilla-Royo, F. Seehusen, J.M. Monné Rodriguez, M. Weisskopf, P.B. Messersmith, U. Möhrlen, L. Vonzuna, M. Ehrbar, N. Ochsenbein-Kölble, “In vivo sealing of fetoscopy-induced fetal membrane defects by mussel glue”, Fetal Diagnosis and Therapy, 49:518–527 (2022). [Link]