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Aug 12, 2023

Bioglue breakthrough

Elie Dolgin is a science journalist in Somerville, Massachusetts. You can also

Elie Dolgin is a science journalist in Somerville, Massachusetts.

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SanaHeal's barnacle-glue-inspired treatment can stop severe bleeding in a pig's liver.Credit: SanaHeal

Sanaheal in Cambridge, Massachusetts, spun off from Massachusetts Institute of Technology, Cambridge, in 2021.

Hyunwoo Yuk lifts the cling film off a lump of purplish tissue and makes a small incision. "This is a beautiful pig liver!" he exclaims.

A mechanical engineer turned entrepreneur, Yuk tries to patch the cut with standard film dressing, but the bandage won't stick — the organ's surface is too moist.

Yuk then applies a small piece of experimental adhesive tape, made using his company's proprietary blend of polymers and chemical compounds. This covering attaches quickly and begins to shrink inwards, pulling the cut closed and adding mechanical reinforcement that, in a living body, would help to promote wound healing.

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First developed in the laboratory of materials scientist Xuanhe Zhao at the Massachusetts Institute of Technology (MIT) in Cambridge, the bioadhesive offers a potential improvement over hand-sewn sutures and existing bleeding-control agents for myriad clinical applications1. In animal testing it has been shown to help seal colon injuries in pigs2, mend skin lesions in mice3 and affix bioelectronics devices onto the beating hearts of rats4. The same sticky tape can also be removed, without causing observable damage to the underlying tissues5.

Yuk describes the technology as a kind of "duct tape for surgery". Just as the plumbing tape is an all-purpose tool for any do-it-yourself enthusiast, his bioadhesive material could provide a universal solution to tissue repair for surgeons.

The tape can also be reformulated into a paste similar to play putty that, when plugged into the damaged livers and hearts of injured animals, produces a watertight seal in seconds6. In experiments with blood-covered pig skin, the closures created by this goo proved stronger than any made by a handful of commercially available adhesives that are designed to do the same thing.

"It really is a versatile platform," says Yuk, who is the chief technology officer of SanaHeal, the spin-off company that he and Zhao — along with physician-scientist Christoph Nabzdyk at Brigham and Women's Hospital in Boston, Massachusetts — created in 2021 to develop the technology further. SanaHeal is a finalist for The Spinoff Prize 2023.

The SanaHeal materials have garnered high praise for their bonding properties and ease of use. "They have a readiness for commercialization and translation that makes them true standouts in the field," says Jianyu Li, a biomaterials engineer at McGill University in Montreal, Canada, who is not involved with the company.

The functionality is especially impressive to Jonathan Wilker, a chemist at Purdue University in West Lafayette, Indiana, given that the technology relies on polymers that are already used in medical devices and therefore are known to be safe. Wilker, who is not involved in the company, points out that SanaHeal arranges those materials in innovative ways that allow for an unprecedented level of stickiness under watery conditions. "The chemistry that they use is nothing terribly exotic," Wilker says, "but they take it to a level that very few people can achieve."

"This represents a significant improvement compared to current wound closure techniques," says Xiaodong Chen, a materials scientist at Nanyang Technological University in Singapore, who is not connected to SanaHeal.

Tissue adhesion wasn't the main objective for Yuk when he joined Zhao's lab group as a graduate student in 2014.

He first earned a master's degree after testing hydrogels — jelly-like mixtures of cross-linked polymers and water — on industrial materials such as glass, ceramics and metals that often require bonding between two wet surfaces. It wasn't until a few years later, after Yuk began his PhD, that the research moved in a more biological direction.

Part of Nature Outlook: The Spinoff Prize 2023

It started with a suggestion from Nabzdyk, who was impressed by Yuk's hydrogels and wanted to try them out in various surgical settings.

Yuk liked the idea. He had always "wanted to do something medical," he says, especially after his younger brother Youngwoo fell from a fifth-floor window in Yuk's home country of South Korea a decade ago, experiencing extensive internal bleeding and requiring multiple operations to survive. The accident gave Yuk a view of the limitations of existing haemorrhage-control options.

Together with Nabzdyk, Yuk began, as he puts it, "solving a really high-stakes problem that could directly benefit patients".

SanaHeal eventually plans to advance its blood-staunching technology for surgical applications. But first, it is pursuing clinical opportunities in which the material doesn't stay inside the body long-term — an area of medicine in which the regulatory path to market is less difficult. Efforts centre around a wound-care patch for foot ulcers in people with diabetes, and a bioadhesive paste for controlling blood loss in emergency trauma situations, such as during military combat.

"These are important clinical problems," says Patrick Rivelli, president and chief executive of SanaHeal, which is in the Kendall Square biotech hub in Cambridge, Massachusetts. Severe bleeding is a leading cause of preventable death in the military, and ulcers cause disability and distress among millions of people worldwide with poorly managed diabetes.

Like SanaHeal's material, other wet-tolerant adhesives in development offer advantages over existing haemostatic products, all of which tend to work slowly and provide only weak seals under messy, blood-soaked conditions. But these rival technologies have their drawbacks. Some require lengthy application periods. Others need irradiation with ultraviolet light to cure the materials.

SanaHeal is aiming for a less demanding user experience. "There's no preparation step needed," says Nabzdyk. "You take it. You press it. And you’re done."

"The simplicity of it is really attractive," says Georgios Theocharidis, a bioengineer at the Beth Israel Deaconess Medical Center in Boston. "It's something that can just be put there and left for several days."

Theocharidis is collaborating with the SanaHeal researchers to test the adhesive patch on diabetic minipigs with ulcer-like open sores. Last year, the researchers showed that bandaging the sores with SanaHeal's self-shrinking, sticky material led to faster skin recovery compared with dressings made from one of the most commonly used wound-care products3. "We see very impressive results," Theocharidis says.

Much of Yuk's work draws inspiration from the natural world. His sticky tape, for example, was designed to mimic how spider webs absorb moisture in a way that helps to trap insects. And his bioadhesive paste is inspired by barnacles, which deploy oily secretions to clean contaminants from surfaces before they lay down adhesive proteins.

In fact, the paste is nothing more than the original sticky tape ground up into tiny pieces and then blended with mineral oil. The oil helps to wick away blood. The microparticles of bioadhesive absorb excess water. And with those confounding liquids out of the way, the material is free to affix tissues and form an impermeable seal that halts the flow of blood from a wound (see ‘Chemical wound-binding’).

Credit: Alisdair MacDonald

"Mechanistically, it does exactly the same thing that barnacle glues do," Yuk says. "This is true bioinspiration."

SanaHeal is dabbling in a number of other speculative applications, such as to facilitate electronic sensor attachment on internal organs or to help reduce the appearance of wrinkles, for example. But in the coming year, the company's main priorities are to expand manufacturing of clinical-grade products as SanaHeal moves closer to commercialization.

It won't be easy. As bioengineer Jeffrey Karp at Brigham and Women's Hospital points out: "One of the biggest challenges is how to scale production of tissue adhesives, achieve a shelf-stable product and not compromise performance in the process." And Karp should know. In 2014, he invented his own surgical glue7, which is now being developed by biotechnology firm Tissium in Paris.

SanaHeal will also need to "consider the long-term performance of these bioadhesives", says Chen. Especially for applications inside the body, for which "finding the right balance between adequate wound closure and decomposition speed is important".

Yuk is well aware of the myriad hurdles that lie ahead. Many before him have tried, and failed, to bring wet-tolerant tissue adhesives into operating rooms and physicians’ offices. "It's an old dragon that everyone wants to slay," he says. But with his sticky tapes and pastes, Yuk might just have created the medical equivalent of Saint George — a dragon-slayer of legendary importance.

doi: https://doi.org/10.1038/d41586-023-01661-2

This article is part of Nature Outlook: The Spinoff Prize 2023, an editorially independent supplement produced with the financial support of third parties. About this content.

Yuk, H. et al. Nature 575, 169–174 (2019).

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