Hydrogels are versatile biomaterials that conquer an increasing number of biomedical areas. Consisting of water-swellable molecular networks that can be engineered to mimic the mechanical and chemical properties of various organs and tissues, they can be applied to both internal and external surfaces of the body without harming even the most delicate parts of the human anatomy. can interface. Hydrogels are already used in clinical practice for the therapeutic delivery of drugs to fight pathogens. as intraocular and contact lenses, and corneal prostheses in ophthalmology; Bone cement, wound dressings, coagulation bandages, and 3D scaffolds in tissue engineering and regeneration.

However, bonding hydrogel polymers together rapidly and strongly remains an unsolved need because conventional methods often result in weak adhesion after the desired adhesion times, and rely on complex procedures. are Achieving rapid adhesion of polymers could enable a number of new applications, including, for example, hydrogels whose stiffness can be tailored to specific tissues, on-demand flexible electronics for medical diagnostics. Encapsulation, or creation of self-adhesive tissue wraps. For tight body parts.

Now, scientists at Harvard University and the Wyss Institute for Biologically Inspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a simple and versatile method to quickly and efficiently bond the same or different layers. Is. Hydrogels and other polymeric materials, using a thin film of chitosan: a fibrous, sugar-based material derived from the processed exoskeleton of shellfish. He successfully applied his new method to several unsolved medical problems, including local protective cooling of tissues, sealing of vascular wounds, and prevention of unwanted “surgical adhesions” of internal body surfaces that adhere to each other. Don’t stick to it. Results are published in Proceedings of the National Academy of Science (PNAS[BB1] ).

“Chitosan films, with their ability to efficiently assemble, repair and protect hydrogels in the body and beyond, are promising for regenerative medicine and surgery,” said David Mooney, senior author and founding Wyss Institute core faculty member. opens countless new opportunities to develop tools for the care of , Ph.D. “The speed, ease and effectiveness with which they can be applied makes them extremely versatile tools and components. aliveThe assembly process often takes short time during surgery, and simple fabrication of complex biomaterial structures in manufacturing facilities.

Engineering a new bond

Over the years, Mooney’s team at the Wyss Institute and SEAS have developed “tough adhesives,” a combination of regenerative medicine methods that strongly adhere to wet tissue surfaces and improve tissue mechanics. uses stretchable hydrogels to facilitate wound healing and tissue regeneration. Properties “Properly designed rigid adhesive and non-adhesive hydrogels offer us and other researchers new opportunities to improve patient care. But to take their functionality one or more steps further, “We wanted to be able to combine two or more hydrogels into more complex assemblies, and to do it quickly, safely, and in a simple process,” co-first author and former Wyss research associate Benjamin Friedman, Ph.D. said Dee, who spearheaded several tough adhesive developments with Mooney. “Existing methods for instantly bonding hydrogels or elastomers had major disadvantages because they relied on toxic adhesives, chemical functionalization of their surfaces, or other complex mechanisms.”

Through a biomaterial screening method, the team identified bridging films made entirely of chitosan. Chitosan is a sugar polymer that can be easily made from the chitin shells of shellfish and has already found its way into a wide range of commercial applications. For example, it is currently used as a seed treatment and as a biopesticide in agriculture, in brewing, in self-healing paint coatings, and to prevent deterioration in medical wound management. .

The team found that chitosan films achieved fast and strong bonding of hydrogels through chemical and physical interactions that are different from traditional hydrogel bonding methods. Instead of forming new chemical bonds based on the sharing of electrons between individual atoms (covalent bonds), due to a small change in pH, the sugar strands of chitosan rapidly absorb the water residing between the hydrogel layers and entangle themselves with the polymer strands of the hydrogels, forming multiple Bonds through Electrostatic interactions and hydrogen bonding (non-covalent bonds). This results in adhesive forces between the hydrogels that are significantly greater than those produced by conventional hydrogel bonding approaches.

First applications.

To demonstrate the breadth of their new method’s potential, the researchers focused on very different clinical challenges. They showed that rigid adhesives modified with chitosan films can now be easily wrapped around cylindrical shapes like an injured finger as self-adhesive bandages to provide better wound care. Due to the high water content of chitosan-bonded hydrogels, their use also allowed for localized cooling of human skin, which could lead to alternative burn treatments in the future.

The researchers also coated hydrogels (hard gels) whose surfaces were modified with thin chitosan films seamlessly around the intestine, tendon, and peripheral nerve tissue without binding to the tissues. “This approach offers the possibility to effectively insulate tissues from each other during surgeries, which can otherwise form ‘fibrotic adhesions’ with sometimes disastrous results. Their prevention is an unmet need. There is a medical need that commercial technology cannot yet adequately address,” Friedman explained.

In another application, they layered a thin chitosan film over a rigid gel that had already been placed on an injured pig aorta. Ex vivo As a wound sealant to increase the overall strength of the bandage, which was exposed to the cyclic mechanical forces of blood pulsation through the vessel.

“The numerous possibilities emerging from this study by Dave Mooney’s group add a new dimension to the engineering of biomedical hydrogel devices, providing elegant solutions to pressing and unsolved problems in regenerative and surgical medicine. may benefit many patients,” said ViceFounding. Director Donald Ingber, MD, PhD, is also Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Hans-Joerg Vice-Professor of Bio-Inspired Engineering In SEAS

Additional study authors are co-first authors Juan Cintron Cruz, Mathew Lee, and James Weaver at the Wyss Institute and SEAS; Phoebe Cowen, Haley Jeffers, and Danielle Kent at SEAS; and Kyle Wu at Beth Israel Deaconess Medical Center in Boston. This study was supported by the Wyss Institute at Harvard University, the National Institute on Aging of the National Institutes of Health (under award # K99/R00AG065495), and the Harvard GSAS Research Scholars Initiative.