Harvard Engineers Unveil Game-Changing Solution for Dural Leakage

Highly adhesive and mechanically strong Dural Tough Adhesive addresses numerous restrictions in the repair work of the dural membrane lining the brain and spine after injury and surgical treatments.

The dural membrane (dura) is the outer of 3 meningeal layers that line the main nerve system (CNS), that includes the brain and spine. Together, the meninges work as a shock-absorber to secure the CNS versus injury, distribute nutrients throughout the CNS, in addition to get rid of waste.

The dura likewise is a crucial biological barrier which contains cerebrospinal fluid (CSF) surrounding all CNS tissues. Consequently, spontaneous injury, injury, or essential surgeries might trigger CSF to leakage, which can threaten clients’ lives, neurological functions, and healing.

“As neurosurgeons, we routinely open the dura to access the brain or spinal cord, but achieving a watertight seal of the dura at the conclusion of these procedures can be challenging in particular circumstances,” stated Kyle Wu, M.D., a neurosurgeon and the co-first and co-corresponding author of a brand-new research study providing an ingenious dural repair work service. “Our current options are limited, consisting of suture repair or grafting, which can be difficult to perform if there is no viable tissue, with large defects, or during minimally invasive surgeries Currently available surgical sealants don’t adhere well to wet tissue, are too brittle, and lack the requisite toughness to reliably prevent CSF leakage.”

Wu now is an Assistant Professor at The Ohio State University Wexner Medical Center, and at the start of the research study was a neurosurgery citizen at the Brigham and Women’s Hospital in Boston and Surgical Innovation Fellow at Boston Children’s Hospital.

A brand-new service to re-sealing the dura has actually now been established by a collective group of bioengineers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), and neurosurgeons at the Brigham and Women’s Hospital, and Ohio State University’s Wexner Medical Center and James Cancer Hospital, which utilizes a multi-functional biomaterial that deals with essential restrictions of existing repair work techniques and has prospective to supplant them.

The scientists, led by Wyss Institute Founding Core Faculty member and SEAS Robert P. Pinkas Family Professor of Bioengineering David Mooney,Ph D., showed that their “Dural Tough Adhesive” (DTA) carried out much better than presently utilized surgical sealants in tests utilizing in vivo animal designs and human-derived tissues ex vivo The findings are released in Science Translational Medicine

Taking motivation from nature

DTAs are an intriguing example of “bioinspired engineering.” Almost a years back, Mooney’s group, which had actually currently collected competence in the style of hydrogels with unique mechanical functions, was trying to find examples in nature that might assist discover brand-new services for sealing and restoring hurt tissues in the body. “Material approaches to tissue regeneration at the time mainly focused on creating strong ‘adhesion’ to various body surfaces, but not so much on strong internal ‘cohesion,’ or toughness in the face of tissue mechanical forces,” stated co-first author Benjamin Freedman,Ph D., a previous Wyss Research Associate on Mooney’s group. “In addition, they remained relatively ineffective in sticking to wet tissue surfaces covered by different body fluids.” Their search led the group to the Dusky Arion slug (Arion subfuscus), which produces an unique type of mucous that it utilizes to quickly glue itself in location to avoid predators from spying it off different surface areas.

In part by imitating residential or commercial properties of the slug’s mucous, the group established a hydrogel including 2 intermixed polymer networks: a network of completely cross-linked acrylamide particles that develops an extremely flexible gel, and a network of reversibly cross-linked alginate particles that can rearrange the energy produced by mechanical forces in underlying tissues. Paired with an extremely adhesive layer that utilizes chitosan, a fibrous, sugar-based compound originated from the external skeletons of shellfish, the composite Tough Adhesive (TA) hydrogel can bond to a range of liquid-covered surface areas by forming numerous kinds of chemical interactions with them that cooperatively produce a tight seal.

“The Mooney group had previously advanced TA approaches for the repair of multiple tissues, including wounded tissue surfaces, tendons, neural tube defects of babies in the womb, and others. When Dr. Wu reached out to us, we embraced dural membrane leakage as a new clinical opportunity for TAs,” stated Freedman, who led numerous TA applications on Mooney’s group.

Improved security for the brain and spine

The group showed that DTA, whose structure follows the very same TA fundamental solution, has repair-relevant functions that transcend to those of existing surgical sealants. In ex vivo research studies, they revealed that DTA adheres substantially more powerful to pigs’ dural membranes and can stand up to greater pressures before stopping working, compared to an industrial sealant. Superior mechanical strength is an essential function of DTAs, because increased intracranial pressure might be come across in conditions such as brain growths, stroke, injury, idiopathic intracranial high blood pressure, and hydrocephalus.

In vivo, when positioned straight onto the dura of rats, DTA kept its structure and was totally biocompatible for a minimum of 4 weeks, triggering just very little inflammation, which was equivalent to business sealants.

The group revealed that DTAs might provide these very same advantages when evaluated utilizing human cadaveric tissue. “In light of the persistent trend toward minimally invasive neurosurgeries for patients’ benefit, an ideal dural sealant must not only be a better alternative to suture repair, but also be easier to handle and deploy in tight spaces – current repair methods are not good at both,” statedWu “In fact, we were able to introduce DTA through the nasal cavity of a human cadaveric cephalus and place it accurately onto a leaking area of the skull base where it withstood artificially generated intracranial pressures that were well beyond the range of even pathological pressures.”

Translating a few of their secret in vitro findings to an in vivo scenario, Mooney, Freedman, Wu, and their coworkers concentrated on a tear in the dural sac covering the spine of pigs. The pig spinal column highly looks like that of human beings. Dural tears are a feared problem throughout spinal column surgical treatment. The group effectively sealed cuts in the dura with a DTA spot, or additionally with the business spinal column sealant DuraSeal as a contrast. Then, they increased the fluid pressure within the spine, using a physiologic maneuver that lots of neurosurgeons carry out to check the stability of dural repair work at the end of surgical treatments. While DTA-repaired cuts never ever experienced any leak with these moderate boosts in fluid pressure, DuraSeal-repaired cuts began dripping in 40% of the cases. In the design, DTA likewise easily withstood leak even when exposed to fluid pressures much greater than those experienced in the body.

“We are excited to have opened a new perspective for neurosurgeons with this study that, in the future, could facilitate a variety of surgical interventions and lower the risk for patients who need to undergo them. This study also underscores how unique and well-understood advances in the design of biomaterials, like the ones we made in our Tough Adhesive platform, have the potential to impact multiple very diverse areas of regenerative medicine,” stated senior author Mooney.

Reference: “A tough bioadhesive hydrogel supports sutureless sealing of the dural membrane in porcine and ex vivo human tissue” by Kyle C. Wu, Benjamin R. Freedman, Phoebe S. Kwon, Matthew Torre, Daniel O. Kent, Wenya Linda Bi and David J. Mooney, 20 March 2024, Science Translational Medicine
DOI: 10.1126/ scitranslmed.adj0616

Other authors on the research study are Wenya Linda Bi, M.D.,Ph D., Associate Professor of Neurosurgery at Harvard Medical School and Brigham and Women’s Hospital, in addition to Phoebe Kwon, Matthew Torre, and DanielKent The work was supported by the Wyss Institute at Harvard University, and < period class ="glossaryLink" aria-describedby ="tt" data-cmtooltip ="<div class=glossaryItemTitle>National Institutes of Health</div><div class=glossaryItemBody>The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.</div>" data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]" tabindex ="0" function =(***************************************************** )> NationalInstitutes ofHealth( under grant # K 99/ R00 AG065495).