Hydrogels have emerged as incredibly versatile biomaterials, revolutionizing various biomedical applications. These water-swollen molecular networks offer a unique opportunity to mimic the mechanical and chemical properties of diverse organs and tissues, facilitating seamless integration within the human body without causing harm, even to the most delicate anatomical structures.
In clinical practice, hydrogels are already making significant strides, serving as vehicles for drug delivery to combat pathogens, as well as being employed in ophthalmology for intraocular and contact lenses, and corneal prostheses. Additionally, they find utility in tissue engineering and regeneration as bone cement, wound dressings, blood-coagulating bandages, and scaffolds for 3D tissue constructs.
Despite their myriad applications, one persistent challenge has been achieving rapid and robust adhesion between hydrogel polymers. Traditional methods often lead to weaker bonds over time and rely on complex procedures.
Addressing this need, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have devised a simple yet versatile solution. They have developed a method to instantly and effectively bond layers of hydrogels and other polymeric materials using a thin film of chitosan—a fibrous, sugar-based material derived from the processed outer skeletons of shellfish.
This innovative approach has already been successfully applied to various medical challenges, including local protective cooling of tissues, sealing of vascular injuries, and preventing unwanted surgical adhesions between internal body surfaces. The research findings have been published in the Proceedings of the National Academy of Sciences.
Senior author and Founding Wyss Institute Core Faculty member, David Mooney, Ph.D., remarked, “Chitosan films offer a myriad of possibilities in regenerative medicine and surgical care, thanks to their ability to assemble, fine-tune, and protect hydrogels both internally and externally.”
He further added, “The simplicity and efficiency of application make them invaluable tools during surgeries, allowing for in vivo assembly processes within short timeframes. Moreover, their ease of fabrication enables the creation of complex biomaterial structures in manufacturing facilities.”
Engineering a new bond
In recent years, Mooney's team at the Wyss Institute and SEAS has pioneered the development of “Tough Adhesives,” a revolutionary approach to regenerative medicine. These stretchable hydrogels have proven instrumental in wound healing and tissue regeneration, thanks to their remarkable ability to adhere strongly to wet tissue surfaces while conforming to the mechanical properties of tissues.
Dr. Benjamin Freedman, co-first author and former Wyss Research Associate, highlighted the potential of Tough Adhesives and non-adhesive hydrogels to enhance patient care. However, the team recognized the need to further enhance their functionalities by enabling the rapid and simple combination of multiple hydrogels in complex assemblies.
Existing methods for bonding hydrogels or elastomers often posed significant challenges, relying on toxic glues, surface chemical functionalization, or complex procedures. Seeking a safer and more efficient solution, the team turned to biomaterial screening and identified chitosan as a promising candidate.
Chitosan, a sugary polymer derived from the chitin shells of shellfish, offered a versatile and biocompatible option. Widely utilized in various commercial applications, including agriculture, winemaking, and medical wound management, chitosan presented an opportunity for rapid and robust bonding of hydrogels.
The team discovered that chitosan films facilitated swift and strong bonding of hydrogels through unique chemical and physical interactions. Unlike traditional bonding methods that rely on the formation of covalent bonds, chitosan's sugar strands quickly absorb water between hydrogel layers, intertwining with polymer strands and forming multiple bonds via electrostatic interactions and hydrogen bonding.
This novel approach results in adhesive forces between hydrogels that far surpass those achieved through conventional bonding methods, paving the way for advanced applications in regenerative medicine and beyond.
First applications
To showcase the versatility of their innovative method, the researchers tackled a diverse range of medical challenges. By incorporating chitosan films into Tough Adhesives, they demonstrated the ability to create self-adhering bandages that can be easily wrapped around cylindrical shapes, such as injured fingers, improving wound care significantly. Moreover, the high water content of chitosan-bonded hydrogels facilitated local cooling of the skin, hinting at potential alternative treatments for burns.
In another application, the researchers seamlessly wrapped chitosan-modified tough gels around bowel, tendon, and peripheral nerve tissues without bonding to the tissues themselves. This technique offers a promising solution for effectively insulating tissues during surgeries, preventing the formation of fibrotic adhesions—a critical clinical need that current technologies struggle to address adequately.
Furthermore, the team applied chitosan-coated tough gels as a wound sealant on an injured pig aorta ex vivo, enhancing the overall strength of the bandage exposed to the cyclical mechanical forces of blood pulsing through the vessel. This highlights the potential of their approach to strengthen wound dressings and improve outcomes in surgical and trauma cases.
Dr. Donald Ingber, Founding Director of the Wyss Institute, emphasized the groundbreaking implications of this study, noting that the myriad possibilities it presents could lead to elegant solutions for urgent unmet challenges in regenerative and surgical medicine, benefiting countless patients.
The collaborative effort involved various contributors, including co-first author Juan Cintron Cruz, Mathew Lee, and James Weaver from the Wyss Institute and SEAS, along with Phoebe Kwon, Haley Jeffers, and Daniel Kent from SEAS, and Kyle Wu from Beth Israel Deaconess Medical Center in Boston.
Source: Harvard University