Scientists create method to bind hydrogels and other polymer materials using chitosan

Hydrogels are versatile biomaterials that are conquering an increasing number of biomedical fields. Made up of water-swollen molecular networks that can be tailored to mimic the mechanical and chemical characteristics of various organs and tissues, they can interface with the body and on its external surfaces without causing damage to even the most delicate parts of human anatomy.

Hydrogels are already used in clinical practice for the therapeutic delivery of drugs to combat pathogens; as intraocular and contact lenses, and corneal prostheses in ophthalmology; bone cement, wound dressings, coagulant bandages and 3D scaffolds for tissue engineering and regeneration.

However, quickly and strongly attaching hydrogel polymers to each other remains an unmet need, as traditional methods often result in weaker adhesion after longer than desired adhesion times and rely on complex procedures.

Achieving rapid adhesion of polymers could enable many new applications, including hydrogels whose stiffness could be finely tuned to better fit specific tissues, on-demand encapsulation of flexible electronic components for diagnostics medical or the creation of self-adhesive tissue wraps. for parts of the body that are difficult to bandage.

Now, scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have created a simple and versatile method to instantly and efficiently bond layers made of the same or different types of hydrogels and other polymeric materials, using a thin film of chitosan: a fibrous sugar-based material derived from the processed outer skeletons of seashells.

The researchers successfully applied their new approach to several unsolved medical problems, including local protective cooling of tissues, sealing vascular lesions, and preventing unwanted “surgical adhesions” of internal body surfaces that should not stick together. to others. The results are published in the Proceedings of the National Academy of Sciences.

“Chitosan films, with their abilities to effectively assemble, refine and protect hydrogels in the body and beyond, open many new opportunities to create devices for regenerative medicine and surgical care,” said David Mooney, lead author and founding faculty member of the Wyss Institute. , Ph.D.

“The speed, ease and efficiency with which they can be applied make them very versatile tools and components for in vivo assembly processes in often short turnaround times during surgical procedures, and for the simple manufacture of structures of complex biomaterials in manufacturing facilities,” Mooney said. who is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

Design a new connection

Over the past several years, Mooney’s team at the Wyss Institute and SEAS has developed “tough adhesives,” a collection of regenerative medicine approaches that use stretchable hydrogels to facilitate wound healing and tissue regeneration by adhering strongly to wet tissue surfaces and conforming to the mechanical stresses of the tissue. properties.

“Precision-formulated strong adhesives and non-adhesive hydrogels offer us and other researchers new opportunities to improve patient care. But to take their functionality one or even several steps further, we wanted to be able to combine two or more hydrogels into more complex assemblies, and do it quickly, safely, and in a simple process,” said Benjamin Freedman, Ph.D., co-first author and former Wyss research associate, who led several developments of heavy duty adhesives with Mooney.

“Existing methods for instantly bonding hydrogels or elastomers had striking drawbacks because they relied on toxic glues, chemical functionalization of their surfaces, or other complex procedures.”

Using a biomaterial screening approach, the team identified bridging films made entirely of chitosan. Chitosan is a sugary polymer that can be easily made from the chitin shells of seashells and has already found its way into many commercial applications. For example, it is currently used to treat seeds and as a biopesticide in agriculture, to prevent spoilage in winemaking, in self-healing paint coatings, and in the treatment of medical wounds.

The team found that chitosan films enabled rapid and strong binding of hydrogels through chemical and physical interactions different from those involved in traditional hydrogel binding methods.

Instead of creating new chemical bonds based on the sharing of electrons between individual atoms (covalent bonds), induced by a small change in pH, the sugar strands of chitosan quickly absorb the water residing between the hydrogel layers and become entangled in the polymer supports of the hydrogels, thereby forming multiple bonds via electrostatic interactions and hydrogen bonds (non-covalent bonds).

This results in adhesion forces between hydrogels that significantly exceed those created by traditional hydrogel bonding approaches.

First applications

To demonstrate the extent of the potential of their new method, the researchers focused on very different medical challenges. They showed that strong adhesives modified with chitosan films could now be easily wrapped around cylindrical shapes like an injured finger as self-adhesive bandages to improve wound care. Due to the high water content of chitosan-linked hydrogels, their application also enabled local cooling of the underlying human skin, which could lead to alternative treatments for burns in the future.

The researchers also wrapped hydrogels (strong gels) whose surfaces were modified with thin films of chitosan seamlessly around the intestine, tendons, and peripheral nerve tissues without binding to the tissues themselves.

“This approach offers the possibility of effectively isolating tissues from each other during surgical procedures, which otherwise can form ‘fibrotic adhesions’ with sometimes devastating consequences. Their prevention is an unmet clinical need that commercial technologies cannot address. not yet respond adequately,” Freedman explained.

In another application, they applied a thin film of chitosan to a tough gel already placed ex vivo on an injured porcine aorta as a sealant to increase the overall strength of the bandage, which was exposed to the cyclic mechanical forces of blood flowing through it. vessel.

“The many possibilities emerging from this study led by Dave Mooney’s group add a new dimension to the engineering of biomedical hydrogel devices, which could lead to elegant solutions to pressing unsolved problems in regenerative and surgical medicine including “Many patients could benefit,” Wyss Founding said. Director Donald Ingber, MD, Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS.

Other authors of the study are co-first author Juan Cintron Cruz, Mathew Lee and James Weaver of the Wyss Institute and SEAS; Phoebe Kwon, Haley Jeffers and Daniel Kent at SEAS; and Kyle Wu at Beth Israel Deaconess Medical Center in Boston.