A tough bioadhesive hydrogel supports sutureless sealing of the dural membrane in porcine and ex vivo human tissue

Author:

Wu Kyle C.12ORCID,Freedman Benjamin R.345ORCID,Kwon Phoebe S.4ORCID,Torre Matthew6ORCID,Kent Daniel O.47ORCID,Bi Wenya Linda1ORCID,Mooney David J.34ORCID

Affiliation:

1. Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

2. Department of Neurosurgery, Wexner Medical Center and James Cancer Hospital, Ohio State University, Columbus, OH 43210, USA.

3. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02139, USA.

4. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02215, USA.

5. Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

6. Department of Neuropathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

7. Department of General Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Abstract

Complete sequestration of central nervous system tissue and cerebrospinal fluid by the dural membrane is fundamental to maintaining homeostasis and proper organ function, making reconstruction of this layer an essential step during neurosurgery. Primary closure of the dura by suture repair is the current standard, despite facing technical, microenvironmental, and anatomic challenges. Here, we apply a mechanically tough hydrogel paired with a bioadhesive for intraoperative sealing of the dural membrane in rodent, porcine, and human central nervous system tissue. Tensile testing demonstrated that this dural tough adhesive (DTA) exhibited greater toughness with higher maximum stress and stretch compared with commercial sealants in aqueous environments. To evaluate the performance of DTA in the range of intracranial pressure typical of healthy and disease states, ex vivo burst pressure testing was conducted until failure after DTA or commercial sealant application on ex vivo porcine dura with a punch biopsy injury. In contrast to commercial sealants, DTA remained adhered to the porcine dura through increasing pressure up to 300 millimeters of mercury and achieved a greater maximum burst pressure. Feasibility of DTA to repair cerebrospinal fluid leak in a simulated surgical context was evaluated in postmortem human dural tissue. DTA supported effective sutureless repair of the porcine thecal sac in vivo. Biocompatibility and adhesion of DTA was maintained for up to 4 weeks in rodents after implantation. The findings suggest the potential of DTA to augment or perhaps even supplant suture repair and warrant further exploration.

Publisher

American Association for the Advancement of Science (AAAS)

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